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51. Sodium orthovanadate overcomes sorafenib resistance of hepatocellular carcinoma cells by inhibiting Na+/K+-ATPase activity and hypoxia-inducible pathways

Author: Weidong Li, Bing Liu, Xueying Sun, Hongchi Jiang, Ping Wang, Wenjing Jiang, Xian Jiang, Guangxin Li, and Peng Xiu
Subjects: 0301 basic medicine, Sorafenib, Male, Vascular Endothelial Growth Factor A, Cell cycle checkpoint, Carcinoma, Hepatocellular, lcsh:Medicine, Antineoplastic Agents, Apoptosis, Article, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Downregulation and upregulation, Cell Line, Tumor, medicine, Animals, Humans, lcsh:Science, Sodium orthovanadate, neoplasms, Cell Proliferation, Adenosine Triphosphatases, Glucose Transporter Type 1, Mice, Inbred BALB C, Multidisciplinary, L-Lactate Dehydrogenase, Chemistry, Cell growth, Kinase, lcsh:R, Liver Neoplasms, digestive system diseases, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Isoenzymes, Vascular endothelial growth factor A, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, lcsh:Q, Lactate Dehydrogenase 5, Vanadates, medicine.drug
Abstract: The resistance to sorafenib highly affects its clinical benefits for treating hepatocellular carcinoma (HCC). Sodium orthovanadate (SOV) is a phosphate analog that displays anti-cancer activities against various types of malignancies including HCC. The present study has demonstrated that SOV is able to overcome sorafenib resistance and strengthens sorafenib in suppressing sorafenib-resistant HCC cells in vitro and in animal models. Similar to its action on parental HCC cells, SOV induced cell cycle arrest at G2/M phases by regulating cyclin B1 and cyclin-dependent kinase 1, and apoptosis by reducing mitochondrial membrane potential, in sorafenib-resistant HCC cells. More importantly, SOV inhibited ATPase activity, which was significantly elevated in sorafenib-resistant HCC cells. SOV also reduced the expression of HIF-1α and HIF-2α and their nuclear translocation, resulting in downregulation of their downstream factors including vascular endothelial growth factor, lactate dehydrogenase-A and glucose transporter 1. Its ability to inhibit ATPase activity and hypoxia-inducible pathways enabled SOV to efficiently suppress both normoxic and hypoxic cells, which compose cancer cell populations inside sorafenib-resistant HCC tumors. The present results indicate that SOV may be a potent candidate drug for overcoming the resistance to sorafenib in treating HCC.
Published: 2018

52. Fertility Drugs Associated with Thyroid Cancer Risk: A Systematic Review and Meta-Analysis

Author: Xiaoying Lv, Yaohua Wu, QingAn Yu, DaKun Ma, Hongchi Jiang, Kunpeng Liu, and Wenjie Dai
Subjects: Infertility, medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, lcsh:Medicine, Fertility, Review Article, General Biochemistry, Genetics and Molecular Biology, Clomiphene, Fertility Agents, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Medicine, Humans, Thyroid Neoplasms, Thyroid cancer, media_common, Fertility drugs, 030219 obstetrics & reproductive medicine, General Immunology and Microbiology, business.industry, Obstetrics, Incidence (epidemiology), Female infertility, lcsh:R, General Medicine, medicine.disease, 030220 oncology & carcinogenesis, Meta-analysis, Relative risk, Female, business, Infertility, Female, Gonadotropins
Abstract: Associations have been demonstrated between fertility drugs and a variety of hormone-sensitive carcinomas. The purpose of this study was to determine the relationship between fertility drugs used in the treatment of female infertility and the risk of thyroid cancer. To investigate the clinical significance of fertility drugs used for the treatment of female infertility and the risk associated with thyroid cancer, we performed a literature search using PubMed, MEDLINE, the Cochrane Library, the Web of Science, and EBSCOHOST for comparative studies published any time prior to July 21, 2017. The studies included women who were treated for infertility with fertility drugs, such as clomiphene citrate, gonadotropins, or other unspecified fertility agents, which reported the incidence of thyroid cancer as the main outcome. Eight studies were included in the meta-analyses. Among women with infertility, there was a significant positive association between thyroid cancer risk and the use of fertility drugs (relative risk [RR] = 1.35; 95% confidence interval [CI] 1.12–1.64; P=0.002). Additionally, among women with infertility, the use of clomiphene citrate was associated with an increased risk of thyroid cancer compared to women who did not use fertility drugs (RR = 1.45; 95% CI 1.12–1.88; P=0.005). After pooling results, we found that the parity status of infertile women using fertility drugs was not associated with thyroid cancer risk (RR = 0.99; 95% CI 0.61–1.58, P=0.95). In summary, clomiphene citrate (the most commonly used fertility drug) and other fertility drugs are associated with an increased risk of thyroid cancer.
Published: 2018

53. PGC1α promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect

Author: Dan Li, Yaohua Wu, Lianxin Liu, Kunpeng Liu, Mingqi Gu, Wenjing Jiang, Ping Sheng, Hongchi Jiang, Panfei Ma, Jihua Han, QingAn Yu, Chaoqun Wang, Jing Sun, Shangha Pan, Yong Ma, Liqian Dong, Yaliang Lan, and Changming Xie
Subjects: 0301 basic medicine, Male, Monocarboxylic Acid Transporters, Cancer Research, Immunology, Mice, Nude, Oxidative phosphorylation, Mitochondrion, Mitochondrial Membrane Transport Proteins, Article, Metastasis, Cholangiocarcinoma, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Downregulation and upregulation, medicine, Animals, Humans, Pyruvate Dehydrogenase (Lipoamide), lcsh:QH573-671, Neoplasm Metastasis, chemistry.chemical_classification, Reactive oxygen species, Mice, Inbred BALB C, lcsh:Cytology, Cell Biology, Metabolism, medicine.disease, Warburg effect, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cell biology, Neoplasm Proteins, Up-Regulation, Gene Expression Regulation, Neoplastic, 030104 developmental biology, chemistry, Mitochondrial biogenesis, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Female, Glycolysis
Abstract: PGC1α acts as a central regulator of mitochondrial metabolism, whose role in cancer progression has been highlighted but remains largely undefined. Especially, it is completely unknown about the effect of PGC1α on cholangiocarcinoma (CCA). Here we showed that PGC1α overexpression had no impact on CCA growth despite the decreased expression of PGC1α in CCA compared with adjacent normal tissue. Instead, PGC1α overexpression-promoted CCA metastasis both in vitro and in vivo. Mechanistically, for the first time, we illuminated that PGC1α reversed the Warburg effect by upregulating the expression of pyruvate dehydrogenase E1 alpha 1 subunit and mitochondrial pyruvate carrier 1 to increase pyruvate flux into the mitochondria for oxidation, whereas simultaneously promoting mitochondrial biogenesis and fusion to mediate the metabolic switch to oxidative phosphorylation. On the one hand, enhanced mitochondrial oxidation metabolism correlated with elevated reactive oxygen species (ROS) production; on the other hand, increased PGC1α expression upregulated the expression levels of mRNA for several ROS-detoxifying enzymes. To this end, the ROS levels, which were elevated but below a critical threshold, did not inhibit CCA cells proliferation. And the moderately increased ROS facilitated metastatic dissemination of CCA cells, which can be abrogated by antioxidants. Our study suggests the potential utility of developing the PGC1α-targeted therapies or blocking PGC1α signaling axis for inhibiting CCA metastasis.
Published: 2018

54. Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122

Author: Huaqiang Zhu, Zheng Wei, Yuetang Mi, Xu Zhou, Xueying Sun, Xian Jiang, Hongchi Jiang, Rui Li, and Jun Lu
Subjects: Male, 0301 basic medicine, Cancer Research, Lung Neoplasms, Cell cycle checkpoint, Cellular differentiation, Blotting, Western, Mice, Nude, Biology, Real-Time Polymerase Chain Reaction, medicine.disease_cause, Cholangiocarcinoma, Immunoenzyme Techniques, Mice, 03 medical and health sciences, Cell Movement, Hepatocyte Nuclear Factor 6, Tumor Cells, Cultured, medicine, Animals, Humans, RNA, Messenger, Transcription factor, Cell Proliferation, Cyclin, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, Cell Cycle, Cell Differentiation, General Medicine, Cell cycle, Xenograft Model Antitumor Assays, Molecular biology, Gene Expression Regulation, Neoplastic, MicroRNAs, Bile Ducts, Intrahepatic, 030104 developmental biology, Bile Duct Neoplasms, Oncology, Cancer research, Carcinogenesis
Abstract: Hepatocyte nuclear factor 6 (HNF6) is a liver-enriched transcription factor and highly expressed in mature bile duct epithelial cells. This study sought to investigate the role of HNF6, particularly the molecular mechanisms for how HNF6 is involved in the growth and metastasis of cholangiocarcinoma (CCA) cells.The expression of HNF6, miR-122 and key molecules was examined by Western blot analysis and real-time RT-PCR. Stable transfectants, HCCC-HNF(low) and RBE-HNF(high), were generated from human CCA HCCC-9810 and RBE cells, respectively. The regulatory effect of HNF6 on miR-122 was evaluated by luciferase reporter assay. Cell proliferation, cycle distribution, migration and invasion were analyzed. The xenograft model was used to assess the effects of HNF6 overexpression on tumorigenesis, growth, metastasis and therapeutic potentials.Human CCA tissues and cells expressed lower levels of HNF6, which positively correlated with miR-122. HNF6 regulated the expression of miR-122 by stimulating its promoter. HNF6 overexpression inhibited cell proliferation by inducing cell cycle arrest at G1 phase through regulating miR-122, cyclin G1 and insulin-like growth factor-1 receptor. HNF6 inhibited the migration and invasion of CCA cells by regulating matrix metalloproteinase-2 and metalloproteinase-9, reversion-inducing-cysteine-rich protein with kazal motifs, E-cadherin and N-cadherin. Co-transfection of anti-miR-122 abrogated the effects of HNF6. HNF6 overexpression inhibited the ability of cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors.The results indicate that HNF6 may serve as a tumor suppressor by regulating miR-122, and its overexpression may represent a mechanism-based therapy for CCA.
Published: 2016
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55. 2ME2 inhibits the activated hypoxia-inducible pathways by cabozantinib and enhances its efficacy against medullary thyroid carcinoma

Author: Xuesong Dong, Haiquan Qiao, Xueying Sun, Hongchi Jiang, Wenjing Jiang, Xian Jiang, Huaqiang Zhu, and Han Lin
Subjects: Male, 0301 basic medicine, Pyridines, Apoptosis, Receptor tyrosine kinase, Tyrosine-kinase inhibitor, Mice, chemistry.chemical_compound, 0302 clinical medicine, Anilides, Hypoxia, Mice, Inbred BALB C, education.field_of_study, Estradiol, biology, General Medicine, Isoenzymes, Vascular endothelial growth factor, Hypoxia-inducible factors, 030220 oncology & carcinogenesis, Female, Hepatocyte growth factor, Signal Transduction, medicine.drug, Adult, medicine.medical_specialty, Cabozantinib, Cell Survival, medicine.drug_class, Lactate dehydrogenase A, Active Transport, Cell Nucleus, Mice, Nude, Antineoplastic Agents, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Thyroid Neoplasms, education, Cell Proliferation, L-Lactate Dehydrogenase, business.industry, Hypoxia-Inducible Factor 1, alpha Subunit, Xenograft Model Antitumor Assays, 2-Methoxyestradiol, Carcinoma, Neuroendocrine, Ki-67 Antigen, 030104 developmental biology, Endocrinology, chemistry, Cancer cell, Cancer research, biology.protein, Lactate Dehydrogenase 5, business, Neoplasm Transplantation
Abstract: Cabozantinib is a multi-targeted tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptor (VEGFR)-2, MET (c-Met, also called hepatocyte growth factor (HGF) receptor), and other receptor tyrosine kinases. Cabozantinib has recently been approved for treating advanced medullary thyroid carcinoma (MTC), but its long-term benefit remains uncertain and dose-dependent adverse events are very common. The present study has demonstrated that 2-methoxyestradiol (2ME2), an inhibitor of hypoxia-inducible factors (HIFs) and a promising anticancer agent under investigation in clinical trials, strengthens anticancer activities of cabozantinib against MTC cells in vitro and in vivo. The activated hypoxia-inducible pathways, which are mainly regulated by HIF-1, contribute to the resistance of hypoxic MTC cells to cabozantinib. Cabozantinib upregulated HIF-1α expression at translational levels and increased the expression of the downstream factors including VEGF, lactate dehydrogenase A (LDHA), HGF, and MET. 2ME2 corrected the activated pathways by cabozantinib through downregulating HIF-1α expression and inhibiting its nuclear translocation in hypoxic MTC cells. Administration of 2ME2 enhanced the efficacy of cabozantinib in suppressing the growth of MTC cell line xenografts and patient-derived xenografts established in mice. Given that 2ME2 targets insensitive hypoxic cancer cells to cabozantinib and can inhibit the activated pathways by cabozantinib, the present results warrant further investigation of 2ME2, particularly in combination with cabozantinib, for the treatment of MTC.
Published: 2015
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56. MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway

Author: De-li Dong, Xueying Sun, Hongchi Jiang, Bo Zhai, Xuesong Dong, Changjun He, Baoxin Li, Xian Jiang, and Shidong Xu
Subjects: phosphatase and tensin homolog, Male, Time Factors, Oligonucleotides, Apoptosis, urologic and male genital diseases, Tensin, heterocyclic compounds, Mice, Inbred BALB C, Liver Neoplasms, Transfection, hepatocellular carcinoma, Hep G2 Cells, Sorafenib, female genital diseases and pregnancy complications, Tumor Burden, Gene Expression Regulation, Neoplastic, Oncology, Hepatocellular carcinoma, miR-21, medicine.drug, Research Paper, Signal Transduction, Niacinamide, autophagy, Carcinoma, Hepatocellular, Mice, Nude, Antineoplastic Agents, Biology, medicine, PTEN, Animals, Humans, Protein kinase B, neoplasms, Protein Kinase Inhibitors, PI3K/AKT/mTOR pathway, Cell Proliferation, Dose-Response Relationship, Drug, Akt, Phenylurea Compounds, Autophagy, PTEN Phosphohydrolase, medicine.disease, Xenograft Model Antitumor Assays, digestive system diseases, Enzyme Activation, MicroRNAs, Drug Resistance, Neoplasm, Cancer research, biology.protein, Proto-Oncogene Proteins c-akt
Abstract: Sorafenib resistance remains a major obstacle for the effective treatments of hepatocellular carcinoma (HCC). Recent studies indicate that activated Akt contributes to the acquired resistance to sorafenib, and miR-21 dysregulates phosphatase and tensin homolog (PTEN), which inhibits Akt activation. Sorafenib-resistant HCC cells were shown to be refractory to sorafenib-induced growth inhibition and apoptosis. Akt and its downstream factors were highly activated and/or upregulated in sorafenib-resistant cells. Inhibition of autophagy decreased the sensitivity of sorafenib-resistant cells to sorafenib, while its induction had the opposite effect. Differential screening of miRNAs showed higher levels of miR-21 in sorafenib-resistant HCC cells. Exposure of HCC cells to sorafenib led to an increase in miR-21 expression, a decrease in PTEN expression and sequential Akt activation. Transfection of miR-21 mimics in HCC cells restored sorafenib resistance by inhibiting autophagy. Anti-miR-21 oligonucleotides re-sensitized sorafenib-resistant cells by promoting autophagy. Inhibition of miR-21 enhances the efficacy of sorafenib in treating sorafenib-resistant HCC tumors in vivo. We conclude that miR-21 participates in the acquired resistance of sorafenib by suppresing autophagy through the Akt/PTEN pathway. MiR-21 could serve as a therapeutic target for overcoming sorafenib resistance in the treatment of HCC.
Published: 2015

57. YAP is a critical oncogene in human cholangiocarcinoma

Author: Yingjian Liang, Yuejin Li, Tongsen Zheng, Lianxin Liu, Huawen Shi, Boshi Sun, Dalong Yin, Yu Sun, Hongchi Jiang, Shangha Pan, Ruipeng Song, Huanlai Wang, Jing Sun, Jiabei Wang, and Tiemin Pei
Subjects: Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Gankyrin, gankyrin, Blotting, Western, information science, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Kaplan-Meier Estimate, Biology, medicine.disease_cause, Metastasis, Cholangiocarcinoma, Cell Line, Tumor, Proto-Oncogene Proteins, parasitic diseases, medicine, Animals, Humans, Neoplasm Invasiveness, Epithelial–mesenchymal transition, cardiovascular diseases, Protein kinase B, PI3K/AKT/mTOR pathway, Adaptor Proteins, Signal Transducing, Mice, Inbred BALB C, Tissue microarray, Oncogene, AKT, fungi, YAP-Signaling Proteins, medicine.disease, Phosphoproteins, Up-Regulation, Gene Expression Regulation, Neoplastic, tumorigenesis, Cell Transformation, Neoplastic, Oncology, Bile Duct Neoplasms, Tissue Array Analysis, biology.protein, Cancer research, cardiovascular system, Heterografts, YAP, Carcinogenesis, Research Paper, Transcription Factors
Abstract: Yes-associated protein (YAP), a transcriptional co-activator, has important regulatory roles in cell signaling and is dysregulated in a number of cancers. However, the role of YAP in cholangiocarcinoma (CCA) progression remains unclear. Here, we demonstrated that YAP was overexpressed in CCA cells and human specimens. High levels of nuclear YAP (nYAP) correlated with histological differentiation, TNM stage, metastasis and poor prognosis in CCA. Silencing YAP increased tumor sensitivity to chemotherapy and inhibited CCA tumorigenesis and metastasis both in vivo and in vitro. YAP overexpression in vivo and in vitro promoted CCA tumorigenesis and metastasis. Additionally, we found that YAP induced epithelial-mesenchymal transition (EMT) and formed a regulatory circuit with miR-29c, IGF1, AKT and gankyrin to promote the progression of CCA. Results of CCA tissue microarray showed positive correlations between nYAP and gankyrin or p-AKT expression. Combination of nYAP and gankyrin or p-AKT exhibited improved prognostic accuracy for CCA patients. In conclusion, YAP promotes carcinogenesis and metastasis by up-regulating gankyrin through activation of the AKT pathway.
Published: 2015

58. Clinicopathologic risk factors for right paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma

Author: DaKun Ma, Wenjie Dai, QingAn Yu, Hongchi Jiang, Yaohua Wu, Kunpeng Liu, Changming Xie, and P. Wang
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Thyroid Lobectomy, Metastasis, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Medicine, Humans, Thyroid Neoplasms, Lymph node, Retrospective Studies, Univariate analysis, business.industry, Thyroid, Thyroidectomy, Middle Aged, medicine.disease, Carcinoma, Papillary, Dissection, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Female, Radiology, Lymph Nodes, business
Abstract: To investigate risk factors associated with right paraesophageal lymph node (RPELN) metastasis in patients with papillary thyroid carcinoma (PTC) and to determine the indications for right lymph node dissection. Clinicopathologic data from 829 patients (104 men and 725 women) with PTC, operated on by the same thyroid surgery team at the First Affiliated Hospital of Harbin Medical University from January 2013 to May 2017, were analyzed. Overall, 309 patients underwent total thyroidectomy with bilateral lymph node dissection, 488 underwent right thyroid lobe and isthmic resection with right central compartment lymph node dissection, and 32 underwent near-total thyroidectomy (ipsilateral thyroid lobectomy with contralateral near-total lobectomy) with bilateral lymph node dissection. The overall rate of central compartment lymph node metastasis was 43.5% (361/829), with right central compartment lymph node and RPELN metastasis rates of 35.5% (294/829) and 19.1% (158/829), respectively. Tumor size, number, invasion, and location, lymph node metastasis, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis were associated with RPELN in the univariate analysis, whereas age and sex were not. Multivariate analysis identified tumors with a diameter ≥ 1 cm, multiple tumors, tumors located in the right lobe, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis as independent risk factors for RPELN metastasis. Lymph node dissection, including RPELN dissection, should be performed for patients with PTC with a tumor diameter ≥ 1 cm, multiple tumors, right-lobe tumors, right central compartment lymph node metastasis, or suspected lateral compartment lymph node metastasis.
Published: 2018

59. The IL-6/STAT3 pathway regulates adhesion molecules and cytoskeleton of endothelial cells in thromboangiitis obliterans

Author: Zheng Wei, Hengzhen Wang, Hali Li, Bo Tang, Bing Liu, Wenjing Jiang, Xueying Sun, and Hongchi Jiang
Subjects: 0301 basic medicine, Adult, Male, STAT3 Transcription Factor, Cell signaling, RHOA, Nitric Oxide Synthase Type III, Vascular Cell Adhesion Molecule-1, Focal adhesion, 03 medical and health sciences, Downregulation and upregulation, Humans, Phosphorylation, STAT3, Cell adhesion, Leg, biology, Cell adhesion molecule, Chemistry, Interleukin-6, Endothelial Cells, Thromboangiitis Obliterans, Acetylation, Cell Biology, Arteries, Middle Aged, Intercellular Adhesion Molecule-1, Cell biology, 030104 developmental biology, Matrix Metalloproteinase 9, Focal Adhesion Kinase 1, STAT protein, biology.protein, rhoA GTP-Binding Protein
Abstract: Thromboangiitis obliterans (TAO) (also known as Buerger's disease) is an inflammatory vascular disease that predominantly affects small- and medium-sized blood vessels of extremities. Endothelial cells play critical roles in the initiation and progression of this disease, but the underlying mechanisms remain unclear. In the present study, we demonstrate that patients with TAO had significantly higher levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in their plasmas, and the involved arterial tissues expressed higher levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), ICAM-1 and VCAM-1. In exploring the molecular mechanisms with human aortic endothelial cells (HAECs), we found that recombinant IL-6 activated the STAT3 pathway, leading to the upregulation and overproduction of ICAM-1 and VCAM-1. RhoA (Ras homolog family member A), eNOS (endothelial nitric oxide synthase) and MMP-9 (matrix metalloproteinase-9) participated in this cellular signaling, and their interaction regulated the expression of ICAM-1 and VCAM-1. The activated STAT3 pathway by IL-6 also modulated the cytoskeleton of HAECs by regulating phosphorylation of focal adhesion kinase (FAK) and acetylation of α-tubulin through interplaying with RhoA. In summary, the present results indicate that activation of the IL-6/STAT3 pathway contributes to the pathogenesis of TAO by regulating cellular adhesion molecules and cytoskeleton of vascular endothelial cells, suggesting that targeting this pathway may provide a potential approach for the management of TAO.
Published: 2017

60. Reciprocal activation between ATPase inhibitory factor 1 and NF-κB drives hepatocellular carcinoma angiogenesis and metastasis

Author: Yingjian Liang, Yuejin Li, Zhaoyang Lu, Tiemin Pei, Xianzhi Meng, Jiyuan Zhu, Youyou Qin, Hongchi Jiang, Huiwen Song, Guangchao Yang, Heng Zhang, Shuai Li, Xuan Song, Shu-Yi Qi, Lianxin Liu, Zhiyong Zhang, Changming Xie, Tongsen Zheng, Dalong Yin, Huawen Shi, Shangha Pan, Ruipeng Song, Boshi Sun, and Jiabei Wang
Subjects: Male, Transcriptional Activation, Vascular Endothelial Growth Factor A, China, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Lung Neoplasms, Angiogenesis, TRAF1, Mice, Nude, Biology, Metastasis, Cohort Studies, Viral Matrix Proteins, Neovascularization, chemistry.chemical_compound, Cell Movement, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Gene silencing, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Neoplasm Metastasis, Mice, Inbred BALB C, Neovascularization, Pathologic, Hepatology, Liver Neoplasms, NF-kappa B, Proteins, Middle Aged, Phosphoproteins, Prognosis, medicine.disease, Vascular endothelial growth factor, chemistry, SNAI1, Cancer research, Female, Snail Family Transcription Factors, medicine.symptom, Transcription Factors
Abstract: Hepatocellular carcinoma (HCC) is a highly vascularized tumor with frequent extrahepatic metastasis. Active angiogenesis and metastasis are responsible for rapid recurrence and poor survival of HCC. However, the mechanisms that contribute to tumor metastasis remain unclear. Here we evaluate the effects of ATPase inhibitory factor 1 (IF1), an inhibitor of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase, on HCC angiogenesis and metastasis. We found that increased expression of IF1 in human HCC predicts poor survival and disease recurrence after surgery. Patients with HCC who have large tumors, with vascular invasion and metastasis, expressed high levels of IF1. Invasive tumors overexpressing IF1 were featured by active epithelial-mesenchymal transition (EMT) and increased angiogenesis, whereas silencing IF1 expression attenuated EMT and invasion of HCC cells. Mechanistically, IF1 promoted Snai1 and vascular endothelial growth factor (VEGF) expression by way of activating nuclear factor kappa B (NF-κB) signaling, which depended on the binding of tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) to NF-κB-inducing kinase (NIK) and the disruption of NIK association with the TRAF2-cIAP2 complex. Suppression of the NF-κB pathway interfered with IF1-mediated EMT and invasion. Chromatin immunoprecipitation assay showed that NF-κB can bind to the Snai1 promoter and trigger its transcription. IF1 was directly transcribed by NF-κB, thus forming a positive feedback signaling loop. There was a significant correlation between IF1 expression and pp65 levels in a cohort of HCC biopsies, and the combination of these two parameters was a more powerful predictor of poor prognosis. Conclusion: IF1 promotes HCC angiogenesis and metastasis by up-regulation of Snai1 and VEGF transcription, thereby providing new insight into HCC progression and IF1 function. (Hepatology 2014;60:1659–1673)
Published: 2014
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61. The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2 (NDRG2)/gp130/STAT3 pathway

Author: Lianxin Liu, Xuan Song, Changming Xie, Shangha Pan, Yingjian Liang, Haiyan Yang, Zhaoyang Lu, Xuehui Hong, Boshi Sun, Tongsen Zheng, Jiabei Wang, Dalong Yin, Hongchi Jiang, Nishant Bhatta, Xianzhi Meng, and Ruipeng Song
Subjects: Male, STAT3 Transcription Factor, Thiosemicarbazones, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Time Factors, Mice, Nude, Antineoplastic Agents, Iron Chelating Agents, Transfection, Metastasis, Transforming Growth Factor beta1, STAT3, Cell Movement, Cell Line, Tumor, Cytokine Receptor gp130, Carcinoma, medicine, Animals, Humans, metastasis, Gene silencing, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Phosphorylation, neoplasms, Dp44mT, biology, Tumor Suppressor Proteins, Liver Neoplasms, NDRG2, hepatocellular carcinoma, Middle Aged, medicine.disease, Xenograft Model Antitumor Assays, digestive system diseases, Gene Expression Regulation, Neoplastic, Oncology, Hepatocellular carcinoma, biology.protein, Cancer research, Female, RNA Interference, N-Myc, Signal Transduction, Research Paper
Abstract: Here we showed that hepatocellular carcinoma (HCC) cell lines with high metastatic potential had low levels of NDRG2. The iron chelator Dp44mT up-regulated NDRG2, suppressed epithelial-mesenchymal transition (EMT) and inhibited tumor metastasis in HCC having high metastatic potential. Also Dp44mT attenuated the TGF-β1-induced EMT in HCC having low metastatic potential. In agreement, silencing endogenous NDRG2 with shNDRG2 in HCC cells attenuated the effect of Dp44mT. We showed that the NDRG2/gp130/STAT3 pathway can mediate Dp44mT effects. In agreement, we found that a combination of NDRG2 expression and p-STAT3 levels is a strong predictor of prognosis in HCC patients. We suggest that up-regulation of NDRG2 by Dp44mT is a promising therapeutic approach in HCC.
Published: 2014
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62. Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in vitro and in an orthotopic model in vivo

Author: Wenjie Dai, Jizhou Wang, Hongchi Jiang, Lianxin Liu, Dawei Wang, Zhilin Xu, Dongsheng Xu, Xiao-yang Zhao, Huayang Pan, Baolei Zhao, Yaohua Wu, Shangha Pan, and Yong Ma
Subjects: Male, Cancer Research, Carcinoma, Hepatocellular, Proliferation index, Cell Survival, Poly ADP ribose polymerase, Mice, Nude, Antineoplastic Agents, Apoptosis, Biology, Mice, chemistry.chemical_compound, Liver Neoplasms, Experimental, In vivo, Autophagy, Animals, Humans, Sodium orthovanadate, Membrane Potential, Mitochondrial, Mice, Inbred BALB C, Hep G2 Cells, Cell cycle, Xenograft Model Antitumor Assays, Molecular biology, In vitro, Tumor Burden, G2 Phase Cell Cycle Checkpoints, Oncology, chemistry, Cancer research, Vanadates
Abstract: The transition metal vanadium is widely distributed in the environment and exhibits various biological and physiological effects in the human body. As a well known vanadium compound, sodium orthovanadate (SOV) has shown promising antineoplastic activity in several human cancers. However, the effects of SOV on liver cancer are still unknown. In this study, for the first time, we showed that SOV could effectively suppress proliferation, induce G2/M cell cycle arrest and apoptosis, and diminish the mitochondrial membrane potential (MMP) of HCC cells in vitro. In addition, our in vitro results were recapitulated in vivo, showing that SOV exhibited a dose-dependent inhibition of growth of human HCC in an orthotopic model, evidenced by the reduction in tumor size, proliferation index and microvessel density, and increase in cell apoptosis. Most important, we found that SOV could inhibit autophagy in HCC cells in vitro and in vivo, which plays a prodeath role. Thus, our findings suggest that SOV could effectively suppress the growth of human HCC through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in HCC treatment.
Published: 2014
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63. Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway

Author: Zengfu Song, Jiachen Lv, Yilong Li, Hongchi Jiang, Shangha Pan, Ji Liu, Liang Ji, Bing Han, Guang Jia, Yueqiu Teng, Yinan Zhou, Bei Sun, and Yongwei Wang
Subjects: Male, Oncology, medicine.medical_specialty, Cell Survival, Mice, Nude, Antineoplastic Agents, Apoptosis, Deoxycytidine, Biochemistry, Mice, chemistry.chemical_compound, Internal medicine, Pancreatic cancer, medicine, Animals, Humans, Cytotoxic T cell, Pharmacology, TUNEL assay, Neovascularization, Pathologic, business.industry, NF-kappa B, Drug Synergism, NF-κB, NFKB1, medicine.disease, Xenograft Model Antitumor Assays, Gemcitabine, Pancreatic Neoplasms, chemistry, Microvessels, Cancer research, Signal transduction, business, Naphthoquinones, Signal Transduction, medicine.drug
Abstract: Although gemcitabine is currently the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer, eventual failure of response is a significant clinical problem. Therefore, novel therapeutic approaches against this disease are highly needed. The aim of this study was to evaluate whether shikonin, a naphthoquinone derivative, has potential in the treatment of pancreatic cancer when used either alone or in combination with gemcitabine. Our in vitro results showed that shikonin inhibited the proliferation of three different human pancreatic cancer cell lines and potentiated the cytotoxic effect of gemcitabine, which correlated with the down-regulation of constitutive as well as gemcitabine-induced activation of NF-κB and NF-κB-regulated gene products. Most importantly, using a xenograft model of human pancreatic cancer, we found shikonin alone significantly suppressed tumor growth and argumented the antitumor activity of gemcitabine. These effects also correlated with the down-regulation of NF-κB activity and its target genes, decreased proliferation (PCNA and Ki-67), decreased microvessel density (CD31), and increased apoptosis (TUNEL) in tumor remnants. Collectively, our results suggest that shikonin can suppress the growth of human pancreatic tumors and potentiate the antitumor effects of gemcitabine through the suppression of NF-κB and NF-κB-regulated gene products.
Published: 2014
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64. Changes in T lymphocyte subsets in mice with CT26 colon tumors after treatment with donor lymphocyte infusion

Author: Tao Jiang, Hongchi Jiang, An-Long Zhu, and Daxun Piao
Subjects: CD4-Positive T-Lymphocytes, Lymphocyte Transfusion, Cyclophosphamide, Lymphocyte, medicine.medical_treatment, Graft vs Host Disease, Mice, Nude, CD8-Positive T-Lymphocytes, Immunotherapy, Adoptive, Donor lymphocyte infusion, Mice, T-Lymphocyte Subsets, Tumor Cells, Cultured, Animals, Transplantation, Homologous, Medicine, Mice, Inbred BALB C, business.industry, General Medicine, T lymphocyte, Immunotherapy, Xenograft Model Antitumor Assays, Survival Rate, Allogeneic Lymphocyte, medicine.anatomical_structure, Colonic Neoplasms, Immunology, Cancer research, Female, business, Spleen, CD8, medicine.drug
Abstract: The objective of this study was to detect changes in T lymphocyte subpopulations in mice with CT26 subcutaneous colon cancer after treatment with donor lymphocyte infusion (DLI) and cyclophosphamide (CP) chemotherapy. A colon cancer model was established by subcutaneous injection of CT26 carcinoma cells into BALB/C mice. The mice were randomized into different treatment groups. We recorded survival times, tumor growth inhibition rates, histopathological changes, and T lymphocyte subsets in peripheral blood of the mice. Mice treated with DLI and CP survived 33.5 ± 5.02 days, which was significantly longer than the survival time of untreated control mice (16.7 ± 2.98 days, P 0.01). In addition, the tumor inhibitory rate was higher in mice treated with DLI and CP (89.3 %) than that in mice treated with CP or DLI alone (67.1 and 34.5 %, respectively). There were higher levels of T lymphocytes that were CD3(+) and CD4(+) in mice treated with DLI alone or the combination of CP and DLI (P 0.05), and the ratio of CD4(+)/CD8(+) cells was significantly improved in these mice (P 0.05). DLI combined with chemotherapy significantly prolonged survival and inhibited tumor growth in mice with CT26 colon cancer. This treatment might also improve immune function in these mice. Donor spleen cells that include high numbers of allogeneic lymphocytes and a few stem cells could induce a graft-versus-tumor effect, leading to elimination of residual cancer cells. This indicates that it is potentially a feasible adoptive cellular immunotherapy strategy for the management of solid tumors.
Published: 2014
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65. 8-methoxysmyrindiol from Gerbera piloselloides (L.) Cass. and its vasodilation effects on isolated rat mesenteric arteries

Author: Huicong Qu, Jianfeng Yang, Weiwei Cao, Yuhua Bai, Xiaohan Cheng, Fa He, Rui Wang, and Hongchi Jiang
Subjects: Male, China, Vasodilator Agents, Vasodilation, Asteraceae, In Vitro Techniques, Pharmacology, 01 natural sciences, Kir channel, chemistry.chemical_compound, Column chromatography, Drug Discovery, Gerbera piloselloides, medicine, Animals, Petroleum ether, Rats, Wistar, Mesenteric arteries, Potential mechanism, Molecular Structure, Plant Extracts, 010405 organic chemistry, General Medicine, Mesenteric Arteries, Rats, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, medicine.anatomical_structure, chemistry, Female, Endothelium, Vascular
Abstract: Gerbera piloselloides (L.) Cass. (Compositae) possesses various biological effects. It is used as an oriental remedy for relieving cough and resolving phlegm. The present study is to investigate the vasodilation effects of Gerbera piloselloides on isolated rat mesenteric arteries (MAs) and the potential mechanism. Different organic extracts of Gerbera piloselloides were tested, and an HPLC-UV-FD-based analytical method was established to identify the active constituents. The principal components, namely, 8-MOP (8-methoxypsoralan) and 8-MSD (8-methoxysmyrindiol), were found to be predominant in the extracts of petroleum ether and dichloroform, which showed stronger vasodilation activities. 8-MSD was isolated from Gerbera piloselloides by silica gel column chromatography coupled with a Waters 2545 high throughput autopurification system, and its vasodilation effects were explored by an assay of tension on rat MA rings. The results suggest that 8-MSD induces vascular relaxation in rat MAs via an endothelium-dependent mechanism involving the Kir channel, which enables Ca2+ entry in the cell and activates production of NO. The present research indicates that 8-MSD may be therapeutically useful as an anti-hypertension agent and to potentially treat cardiovascular and gastrointestinal diseases.
Published: 2019
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66. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Author: Daniel J. Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M. Adams, Peter D. Adams, Khosrow Adeli, Peter J. Adhihetty, Sharon G. Adler, Galila Agam, Rajesh Agarwal, Manish K. Aghi, Maria Agnello, Patrizia Agostinis, Patricia V. Aguilar, Julio Aguirre Ghiso, Edoardo M. Airoldi, Slimane Ait Si Ali, Takahiko Akematsu, Emmanuel T. Akporiaye, Mohamed Al Rubeai, Guillermo M. Albaiceta, Chris Albanese, Diego Albani, Matthew L. Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte Beceril, Emad S. Alnemri, Covadonga Alonso, Nihal Altan Bonnet, Dario C. Altieri, Silvia Alvarez, Lydia Alvarez Erviti, Sandro Alves, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O. Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A. Anania, Stig U. Andersen, Usha P. Andley, Catherine K. Andreadi, Nathalie Andrieu Abadie, Alberto Anel, David K. Ann, Shailendra Anoopkumar Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Arias, Hirokazu Arimoto, Aileen R. Ariosa, Jane L. Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askanas, Eric Asselin, Ryuichiro Atarashi, Sally S. Atherton, Julie D. Atkin, Laura D. Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M. Backer, Dong Hun Bae, Jae sung Bae, Ok Nam Bae, Soo Han Bae, Eric H. Baehrecke, Seung Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska Zadworna, Hua Bai, Jie Bai, Xue Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D. Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C. Bassham, Maria Teresa Bassi, Robert C. Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L. Baumgarner, K. Ulrich Bayer, Rupert Beale, Jean François Beaulieu, George R. Beck Jr, Christoph Becker, J. David Beckham, Pierre André Bédard, Patrick J. Bednarski, Thomas J. Begley, Christian Behl, Christian Behrends, Georg MN Behrens, Kevin E. Behrns, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S. Bess, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K. Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard Piechaczyk, Viktor Billes, Claudia Bincoletto, Baris Bingol, Sara W. Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A. Blanco, Heidi Kiil Blomhoff, Emilio Boada Romero, Stefan Böckler, Marianne Boes, Kathleen Boesze Battaglia, Lawrence H. Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M. Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie Josée Boucher, Michael E. Boulton, Sebastien G. Bouret, Patricia Boya, Michaël Boyer Guittaut, Peter V. Bozhkov, Nathan Brady, Vania MM Braga, Claudio Brancolini, Gerhard H. Braus, José M. Bravo San Pedro, Lisa A. Brennan, Emery H. Bresnick, Patrick Brest, Dave Bridges, MarieAgnès Bringer, Marisa Brini, Glauber C. Brito, Bertha Brodin, Paul S. Brookes, Eric J. Brown, Karen Brown, Hal E. Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H. Brumell, Nicola Brunetti Pierri, Robert J. Bryson Richardson, Shilpa Buch, Alastair M. Buchan, Hikmet Budak, Dmitry V. Bulavin, Scott J. Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E. Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R. Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B. Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S. Carew, Laura A. Carleton, Cathleen R. Carlin, Silvia Carloni, Sven R. Carlsson, Didac Carmona Gutierrez, Leticia AM Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casas, Josefina Casas, Giuliana Cassinelli, Perrine Castets, Susana Castro Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I. Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, CETRULLO, SILVIA, Hassan Chaachouay, Han Jung Chae, Andrei S. Chagin, Chee Yin Chai, Gopal Chakrabarti, Georgios Chamilos, Edmond YW Chan, Matthew TV Chan, Dhyan Chandra, Pallavi Chandra, Chih Peng Chang, Raymond Chuen Chung Chang, Ta Yuan Chang, John C. Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E. Cheetham, Rajkumar Cheluvappa, Chun Jung Chen, Gang Chen, Guang Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W. Chen, Jian Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang Der Chen, Si Chen, Steve S. L. 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Devenish, Sabrina Di Bartolomeo, Nicola Di Daniele, Fabio Di Domenico, Alessia Di Nardo, Simone Di Paola, Antonio Di Pietro, Livia Di Renzo, Aaron DiAntonio, Guillermo Díaz Araya, Ines Díaz Laviada, Maria T. Diaz Meco, Javier Diaz Nido, Chad A. Dickey, Robert C. Dickson, Marc Diederich, Paul Digard, Ivan Dikic, Savithrama P. Dinesh Kumar, Chan Ding, Wen Xing Ding, Zufeng Ding, Luciana Dini, Jörg HW Distler, Abhinav Diwan, Mojgan Djavaheri Mergny, Kostyantyn Dmytruk, Renwick CJ Dobson, Volker Doetsch, Karol Dokladny, Svetlana Dokudovskaya, Massimo Donadelli, X. Charlie Dong, Xiaonan Dong, Zheng Dong, Terrence M. Donohue Jr, Kelly S. Doran, Gabriella D'Orazi, Gerald W. Dorn II, Victor Dosenko, Sami Dridi, Liat Drucker, Jie Du, Li Lin Du, Lihuan Du, André du Toit, Priyamvada Dua, Lei Duan, Pu Duann, Vikash Kumar Dubey, Michael R. Duchen, Michel A. Duchosal, Helene Duez, Isabelle Dugail, Verónica I. Dumit, Mara C. Duncan, Elaine A. Dunlop, William A. Dunn Jr, Nicolas Dupont, Luc Dupuis, Raúl V. Durán, Thomas M. Durcan, Stéphane Duvezin Caubet, Umamaheswar Duvvuri, Vinay Eapen, Darius Ebrahimi Fakhari, Arnaud Echard, Leopold Eckhart, Charles L. Edelstein, Aimee L. Edinger, Ludwig Eichinger, Tobias Eisenberg, Avital Eisenberg Lerner, N. Tony Eissa, Wafik S. El Deiry, Victoria El Khoury, Zvulun Elazar, Hagit Eldar Finkelman, Chris JH Elliott, Enzo Emanuele, Urban Emmenegger, Nikolai Engedal, Anna Mart Engelbrecht, Simone Engelender, Jorrit M. Enserink, Ralf Erdmann, Jekaterina Erenpreisa, Rajaraman Eri, Jason L. Eriksen, Andreja Erman, Ricardo Escalante, Eeva Liisa Eskelinen, Lucile Espert, Lorena Esteban Martínez, Thomas J. Evans, Mario Fabri, Gemma Fabrias, Cinzia Fabrizi, Antonio Facchiano, Nils J. Færgeman, Alberto Faggioni, W. Douglas Fairlie, Chunhai Fan, Daping Fan, Jie Fan, Shengyun Fang, Manolis Fanto, Alessandro Fanzani, Thomas Farkas, Mathias Faure, Francois B. Favier, Howard Fearnhead, Massimo Federici, Erkang Fei, Tania C. Felizardo, Hua Feng, Yibin Feng, Yuchen Feng, Thomas A. Ferguson, Álvaro F. Fernández, Maite G. Fernandez Barrena, Jose C. Fernandez Checa, Arsenio Fernández López, Martin E. Fernandez Zapico, Olivier Feron, Elisabetta Ferraro, Carmen Veríssima Ferreira Halder, Laszlo Fesus, Ralph Feuer, Fabienne C. Fiesel, Eduardo C. Filippi Chiela, Giuseppe Filomeni, Gian Maria Fimia, John H. Fingert, Steven Finkbeiner, Toren Finkel, Filomena Fiorito, Paul B. Fisher, Marc Flajolet, FLAMIGNI, FLAVIO, Oliver Florey, Salvatore Florio, R. Andres Floto, Marco Folini, Carlo Follo, Edward A. Fon, Francesco Fornai, Franco Fortunato, Alessandro Fraldi, Rodrigo Franco, Arnaud Francois, Aurélie François, Lisa B. Frankel, Iain DC Fraser, Norbert Frey, Damien G. Freyssenet, Christian Frezza, Scott L. Friedman, Daniel E. Frigo, Dongxu Fu, José M. Fuentes, Juan Fueyo, Yoshio Fujitani, Yuuki Fujiwara, Mikihiro Fujiya, Mitsunori Fukuda, Simone Fulda, Carmela Fusco, Bozena Gabryel, Matthias Gaestel, Philippe Gailly, Malgorzata Gajewska, Sehamuddin Galadari, Gad Galili, Inmaculada Galindo, Maria F. Galindo, Giovanna Galliciotti, Lorenzo Galluzzi, Luca Galluzzi, Vincent Galy, Noor Gammoh, Sam Gandy, Anand K. Ganesan, Swamynathan Ganesan, Ian G. Ganley, Monique Gannagé, Fen Biao Gao, Feng Gao, Jian Xin Gao, Lorena García Nannig, Eleonora García Véscovi, Marina Garcia Macía, Carmen Garcia Ruiz, Abhishek D. Garg, Pramod Kumar Garg, Ricardo Gargini, Nils Christian Gassen, Damián Gatica, Evelina Gatti, Julie Gavard, Evripidis Gavathiotis, Liang Ge, Pengfei Ge, Shengfang Ge, Po Wu Gean, Vania Gelmetti, Armando A. Genazzani, Jiefei Geng, Pascal Genschik, Lisa Gerner, Jason E. Gestwicki, David A. Gewirtz, Saeid Ghavami, Eric Ghigo, Debabrata Ghosh, Anna Maria Giammarioli, Francesca Giampieri, Claudia Giampietri, Alexandra Giatromanolaki, Derrick J. Gibbings, Lara Gibellini, Spencer B. Gibson, Vanessa Ginet, Antonio Giordano, Flaviano Giorgini, Elisa Giovannetti, Stephen E. Girardin, Suzana Gispert, Sandy Giuliano, Candece L. Gladson, Alvaro Glavic, Martin Gleave, Nelly Godefroy, Robert M. Gogal Jr, Kuppan Gokulan, Gustavo H. Goldman, Delia Goletti, Michael S. Goligorsky, Aldrin V. Gomes, Ligia C. Gomes, Hernando Gomez, Candelaria Gomez Manzano, Rubén Gómez Sánchez, Dawit AP Gonçalves, Ebru Goncu, Qingqiu Gong, Céline Gongora, Carlos B. Gonzalez, Pedro Gonzalez Alegre, Pilar Gonzalez Cabo, Rosa Ana González Polo, Ing Swie Goping, Carlos Gorbea, Nikolai V. Gorbunov, Daphne R. Goring, Adrienne M. Gorman, Sharon M. Gorski, Sandro Goruppi, Shino Goto Yamada, Cecilia Gotor, Roberta A. Gottlieb, Illana Gozes, Devrim Gozuacik, Yacine Graba, Martin Graef, Giovanna E. Granato, Gary Dean Grant, Steven Grant, Giovanni Luca Gravina, Douglas R. Green, Alexander Greenhough, Michael T. Greenwood, Benedetto Grimaldi, Frédéric Gros, Charles Grose, Jean Francois Groulx, Florian Gruber, Paolo Grumati, Tilman Grune, Jun Lin Guan, Kun Liang Guan, Barbara Guerra, Carlos Guillen, Kailash Gulshan, Jan Gunst, Chuanyong Guo, Lei Guo, Ming Guo, Wenjie Guo, Xu Guang Guo, Andrea A. Gust, Åsa B. Gustafsson, Elaine Gutierrez, Maximiliano G. Gutierrez, Ho Shin Gwak, Albert Haas, James E. Haber, Shinji Hadano, Monica Hagedorn, David R. Hahn, Andrew J. Halayko, Anne Hamacher Brady, Kozo Hamada, Ahmed Hamai, Andrea Hamann, Maho Hamasaki, Isabelle Hamer, Qutayba Hamid, Ester M. Hammond, Feng Han, Weidong Han, James T. Handa, John A. Hanover, Malene Hansen, Masaru Harada, Ljubica Harhaji Trajkovic, J. Wade Harper, Abdel Halim Harrath, Adrian L. Harris, James Harris, Udo Hasler, Peter Hasselblatt, Kazuhisa Hasui, Robert G. Hawley, Teresa S. Hawley, Congcong He, Cynthia Y. He, Fengtian He, Gu He, Rong Rong He, Xian Hui He, You Wen He, Yu Ying He, Joan K. Heath, Marie Josée Hébert, Robert A. Heinzen, Gudmundur Vignir Helgason, Michael Hensel, Elizabeth P. Henske, Chengtao Her, Paul K. Herman, Agustín Hernández, Carlos Hernandez, Sonia Hernández Tiedra, Claudio Hetz, P. Robin Hiesinger, Katsumi Higaki, Sabine Hilfiker, Bradford G. Hill, Joseph A. Hill, William D. Hill, Keisuke Hino, Daniel Hofius, Paul Hofman, Günter U. Höglinger, Jörg Höhfeld, Marina K. Holz, Yonggeun Hong, David A. Hood, Jeroen JM Hoozemans, Thorsten Hoppe, Chin Hsu, Chin Yuan Hsu, Li Chung Hsu, Dong Hu, Guochang Hu, Hong Ming Hu, Hongbo Hu, Ming Chang Hu, Yu Chen Hu, Zhuo Wei Hu, Fang Hua, Ya Hua, Canhua Huang, Huey Lan Huang, Kuo How Huang, Kuo Yang Huang, Shile Huang, Shiqian Huang, Wei Pang Huang, Yi Ran Huang, Yong Huang, Yunfei Huang, Tobias B. Huber, Patricia Huebbe, Won Ki Huh, Juha J. Hulmi, Gang Min Hur, James H. 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King, Karla Kirkegaard, Vladimir Kirkin, Lorrie A. Kirshenbaum, Shuji Kishi, Yasuo Kitajima, Katsuhiko Kitamoto, Yasushi Kitaoka, Kaio Kitazato, Rudolf A. Kley, Walter T. Klimecki, Michael Klinkenberg, Jochen Klucken, Helene Knævelsrud, Erwin Knecht, Laura Knuppertz, Jiunn Liang Ko, Satoru Kobayashi, Jan C. Koch, Christelle Koechlin Ramonatxo, Ulrich Koenig, Young Ho Koh, Katja Köhler, Sepp D. Kohlwein, Masato Koike, Masaaki Komatsu, Eiki Kominami, Dexin Kong, Hee Jeong Kong, Eumorphia G. Konstantakou, Benjamin T. Kopp, Tamas Korcsmaros, Laura Korhonen, Viktor I. Korolchuk, Nadya V. Koshkina, Yanjun Kou, Michael I. Koukourakis, Constantinos Koumenis, Attila L. Kovács, Tibor Kovács, Werner J. Kovacs, Daisuke Koya, Claudine Kraft, Dimitri Krainc, Helmut Kramer, Tamara Kravic Stevovic, Wilhelm Krek, Carole Kretz Remy, Roswitha Krick, Malathi Krishnamurthy, Janos Kriston Vizi, Guido Kroemer, Michael C. Kruer, Rejko Kruger, Nicholas T. Ktistakis, Kazuyuki Kuchitsu, Christian Kuhn, Addanki Pratap Kumar, Anuj Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Rakesh Kumar, Sharad Kumar, Mondira Kundu, Hsing Jien Kung, Atsushi Kuno, Sheng Han Kuo, Jeff Kuret, Tino Kurz, Terry Kwok, Taeg Kyu Kwon, Yong Tae Kwon, Irene Kyrmizi, Albert R. La Spada, Frank Lafont, Tim Lahm, Aparna Lakkaraju, Truong Lam, Trond Lamark, Steve Lancel, Terry H. Landowski, Darius JR Lane, Jon D. Lane, Cinzia Lanzi, Pierre Lapaquette, Louis R. Lapierre, Jocelyn Laporte, Johanna Laukkarinen, Gordon W. Laurie, Sergio Lavandero, Lena Lavie, Matthew J. LaVoie, Betty Yuen Kwan Law, Helen Ka wai Law, Kelsey B. Law, Robert Layfield, Pedro A. Lazo, Laurent Le Cam, Karine G. Le Roch, Hervé Le Stunff, Vijittra Leardkamolkarn, Marc Lecuit, Byung Hoon Lee, Che Hsin Lee, Erinna F. Lee, Gyun Min Lee, He Jin Lee, Hsinyu Lee, Jae Keun Lee, Jongdae Lee, Juhyun Lee, Jun Hee Lee, Michael Lee, Myung Shik Lee, Patty J. Lee, Sam W. Lee, Seung Jae Lee, Shiow Ju Lee, Stella Y. Lee, Sug Hyung Lee, Sung Sik Lee, Sung Joon Lee, Sunhee Lee, Ying Ray Lee, Yong J. Lee, Young H. Lee, Christiaan Leeuwenburgh, Sylvain Lefort, Renaud Legouis, Jinzhi Lei, Qun Ying Lei, David A. Leib, Gil Leibowitz, Istvan Lekli, Stéphane D. Lemaire, John J. Lemasters, Marius K. Lemberg, Antoinette Lemoine, Shuilong Leng, Guido Lenz, Paola Lenzi, Lilach O. Lerman, Daniele Lettieri Barbato, Julia I. Ju Leu, Hing Y. Leung, Beth Levine, Patrick A. Lewis, Frank Lezoualc'h, Chi Li, Faqiang Li, Feng Jun Li, Jun Li, Ke Li, Lian Li, Min Li, Qiang Li, Rui Li, Sheng Li, Wei Li, Xiaotao Li, Yumin Li, Jiqin Lian, Chengyu Liang, Qiangrong Liang, Yulin Liao, Joana Liberal, Pawel P. Liberski, Pearl Lie, Andrew P. Lieberman, Hyunjung Jade Lim, Kah Leong Lim, Kyu Lim, Raquel T. Lima, Chang Shen Lin, Chiou Feng Lin, Fang Lin, Fangming Lin, Fu Cheng Lin, Kui Lin, Kwang Huei Lin, Pei Hui Lin, Tianwei Lin, Wan Wan Lin, Yee Shin Lin, Yong Lin, Rafael Linden, Dan Lindholm, Lisa M. Lindqvist, Paul Lingor, Andreas Linkermann, Lance A. Liotta, Marta M. Lipinski, Vitor A. Lira, Michael P. Lisanti, Paloma B. Liton, Bo Liu, Chong Liu, Chun Feng Liu, Fei Liu, Hung Jen Liu, Jianxun Liu, Jing Jing Liu, Jing Lan Liu, Ke Liu, Leyuan Liu, Liang Liu, Quentin Liu, Rong Yu Liu, Shiming Liu, Shuwen Liu, Wei Liu, Xian De Liu, Xiangguo Liu, Xiao Hong Liu, Xinfeng Liu, Xu Liu, Xueqin Liu, Yang Liu, Yule Liu, Zexian Liu, Zhe Liu, Juan P. Liuzzi, Gérard Lizard, Mila Ljujic, Irfan J. Lodhi, Susan E. Logue, Bal L. Lokeshwar, Yun Chau Long, Sagar Lonial, Benjamin Loos, Carlos López Otín, Cristina López Vicario, Mar Lorente, Philip L. Lorenzi, Péter Lõrincz, Marek Los, Michael T. Lotze, Penny E. Lovat, Binfeng Lu, Bo Lu, Jiahong Lu, Qing Lu, She Min Lu, Shuyan Lu, Yingying Lu, Frédéric Luciano, Shirley Luckhart, John Milton Lucocq, Paula Ludovico, Aurelia Lugea, Nicholas W. Lukacs, Julian J. Lum, Anders H. Lund, Honglin Luo, Jia Luo, Shouqing Luo, Claudio Luparello, Timothy Lyons, Jianjie Ma, Yi Ma, Yong Ma, Zhenyi Ma, Juliano Machado, Glaucia M. Machado Santelli, Fernando Macian, Gustavo C. MacIntosh, Jeffrey P. MacKeigan, Kay F. Macleod, John D. MacMicking, Lee Ann MacMillan Crow, Frank Madeo, Muniswamy Madesh, Julio Madrigal Matute, Akiko Maeda, Tatsuya Maeda, Gustavo Maegawa, Emilia Maellaro, Hannelore Maes, Marta Magariños, Kenneth Maiese, Tapas K. Maiti, Luigi Maiuri, Maria Chiara Maiuri, Carl G. Maki, Roland Malli, Walter Malorni, Alina Maloyan, Fathia Mami Chouaib, Na Man, Joseph D. Mancias, Eva Maria Mandelkow, Michael A. Mandell, Angelo A. Manfredi, Serge N. Manié, Claudia Manzoni, Kai Mao, Zixu Mao, Zong Wan Mao, Philippe Marambaud, Anna Maria Marconi, Zvonimir Marelja, Gabriella Marfe, Marta Margeta, Eva Margittai, Muriel Mari, Francesca V. Mariani, Concepcio Marin, Sara Marinelli, Guillermo Mariño, Ivanka Markovic, Rebecca Marquez, MARTELLI, ALBERTO MARIA, Sascha Martens, Katie R. Martin, Seamus J. Martin, Shaun Martin, Miguel A. Martin Acebes, Paloma Martín Sanz, Camille Martinand Mari, Wim Martinet, Jennifer Martinez, Nuria Martinez Lopez, Ubaldo Martinez Outschoorn, Moisés Martínez Velázquez, Marta Martinez Vicente, Waleska Kerllen Martins, Hirosato Mashima, James A. Mastrianni, Giuseppe Matarese, Paola Matarrese, Roberto Mateo, Satoaki Matoba, Naomichi Matsumoto, Takehiko Matsushita, Akira Matsuura, Takeshi Matsuzawa, Mark P. Mattson, Soledad Matus, Norma Maugeri, Caroline Mauvezin, Andreas Mayer, Dusica Maysinger, Guillermo D. Mazzolini, Mary Kate McBrayer, Kimberly McCall, Craig McCormick, Gerald M. McInerney, Skye C. McIver, Sharon McKenna, John J. McMahon, Iain A. McNeish, Fatima Mechta Grigoriou, Jan Paul Medema, Diego L. Medina, Klara Megyeri, Maryam Mehrpour, Jawahar L. Mehta, Yide Mei, Ute Christiane Meier, Alfred J. Meijer, Alicia Meléndez, Gerry Melino, Sonia Melino, Edesio Jose Tenorio de Melo, Maria A. Mena, Marc D. Meneghini, Javier A. Menendez, Regina Menezes, Liesu Meng, Ling hua Meng, Songshu Meng, Rossella Menghini, A. Sue Menko, Rubem FS Menna Barreto, Manoj B. Menon, Marco A. Meraz Ríos, Giuseppe Merla, Luciano Merlini, Angelica M. Merlot, Andreas Meryk, Stefania Meschini, Joel N. Meyer, Man tian Mi, Chao Yu Miao, Lucia Micale, Simon Michaeli, Carine Michiels, FRANCO MIGLIACCIO, ANNA RITA, Anastasia Susie Mihailidou, Dalibor Mijaljica, Katsuhiko Mikoshiba, Enrico Milan, Leonor Miller Fleming, Gordon B. Mills, Ian G. Mills, Georgia Minakaki, Berge A. Minassian, Xiu Fen Ming, Farida Minibayeva, Elena A. Minina, Justine D. Mintern, Saverio Minucci, Antonio Miranda Vizuete, Claire H. Mitchell, Shigeki Miyamoto, Keisuke Miyazawa, Noboru Mizushima, Katarzyna Mnich, Baharia Mograbi, Simin Mohseni, Luis Ferreira Moita, Marco Molinari, Maurizio Molinari, Andreas Buch Møller, Bertrand Mollereau, Faustino Mollinedo, Marco Mongillo, Martha M. Monick, Serena Montagnaro, Craig Montell, Darren J. Moore, Michael N. Moore, Rodrigo Mora Rodriguez, Paula I. Moreira, Etienne Morel, Maria Beatrice Morelli, Sandra Moreno, Michael J. Morgan, Arnaud Moris, Yuji Moriyasu, Janna L. Morrison, Lynda A. Morrison, Eugenia Morselli, Jorge Moscat, Pope L. Moseley, Serge Mostowy, Elisa Motori, Denis Mottet, Jeremy C. Mottram, Charbel E. H. Moussa, Vassiliki E. Mpakou, Hasan Mukhtar, Jean M. Mulcahy Levy, Sylviane Muller, Raquel Muñoz Moreno, Cristina Muñoz Pinedo, Christian Münz, Maureen E. Murphy, James T. Murray, Aditya Murthy, Indira U. Mysorekar, Ivan R. Nabi, Massimo Nabissi, Gustavo A. Nader, Yukitoshi Nagahara, Yoshitaka Nagai, Kazuhiro Nagata, Anika Nagelkerke, Péter Nagy, Samisubbu R. Naidu, Sreejayan Nair, Hiroyasu Nakano, Hitoshi Nakatogawa, Meera Nanjundan, Gennaro Napolitano, Naweed I. Naqvi, Roberta Nardacci, Derek P. Narendra, Masashi Narita, Anna Chiara Nascimbeni, Ramesh Natarajan, Luiz C. Navegantes, Steffan T. Nawrocki, Taras Y. Nazarko, Volodymyr Y. Nazarko, Thomas Neill, Luca M. Neri, Mihai G. Netea, Romana T. Netea Maier, Bruno M. Neves, Paul A. Ney, Ioannis P. Nezis, Hang TT Nguyen, Huu Phuc Nguyen, Anne Sophie Nicot, Hilde Nilsen, Per Nilsson, Mikio Nishimura, Ichizo Nishino, Mireia Niso Santano, Hua Niu, Ralph A. Nixon, Vincent CO Njar, Takeshi Noda, Angelika A. Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K. Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B. O'Donnell, Tracey O'Donovan, Peter J. O'Dwyer, Ina Oehme, Clara L. Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J. Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F. Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P. Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J. O'Rourke, Helena Orozco, Angel L. Ortega, Elena Ortona, Laura D. Osellame, Junko Oshima, Shigeru Oshima, Heinz D. Osiewacz, Takanobu Otomo, Kinya Otsu, Jing hsiung James Ou, Tiago F. Outeiro, Dong yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A. Ozbun, P. Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Pages, Ugo Pagnini, Beata Pajak, Stephen C. Pak, Karolina Pakos Zebrucka, Nazzy Pakpour, Zdena Palková, Francesca Palladino, Kathrin Pallauf, Nicolas Pallet, Marta Palmieri, Søren R. Paludan, Camilla Palumbo, Silvia Palumbo, Olatz Pampliega, Hongming Pan, Wei Pan, Theocharis Panaretakis, Aseem Pandey, Areti Pantazopoulou, Zuzana Papackova, Daniela L. 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Voth, Valérie Vouret Craviari, Kristina Vuori, Jatin M. Vyas, Christian Waeber, Cheryl Lyn Walker, Mark J. Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai jie Wang, Haichao Wang, Hong Gang Wang, Hongmin Wang, Horng Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei Qing Wang, Pei Yu Wang, Peng Wang, Richard C. Wang, Shuo Wang, Ting Fang Wang, Xian Wang, Xiao jia Wang, Xiao Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warnes, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E. Full Terms, Conditions of access, use can be found at h.t.t.p.:././.w.w.w. t.a.n.d.f.o.n.l.i.n.e. com/action/journalInformation?journalCode=kaup20 Download by: [Alma Mater Studiorum Università di Bologna] Date: 23 September 2016, At: 06:43 Weaver, Colin D. Weekes, Jiwu Wei, Thomas Weide, Conrad C. Weihl, Günther Weindl, Simone Nardin Weis, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M. Weyand, Anthony R. White, Eileen White, J. Lindsay Whitton, Alexander J. Whitworth, Joëlle Wiels, Franziska Wild, Manon E. Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris Williams, Katherine Williams, Peter R. Williamson, Konstanze F. Winklhofer, Steven S. Witkin, Stephanie E. Wohlgemuth, Thomas Wollert, Ernst J. Wolvetang, Esther Wong, G. William Wong, Richard W. Wong, Vincent Kam Wai Wong, Elizabeth A. Woodcock, Karen L. Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William KK Wu, Yaohua Wu, Zhenlong Wu, Cristina PR Xavier, Ramnik J. Xavier, Gui Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun Sheng Yang, Jin Ming Yang, Liu Yang, Minghua Yang, Pei Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng Chao Yao, Pamela J. Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S. Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S. Yeh, Patricia L. Yeyati, Fan Yi, Long Yi, Xiao Ming Yin, Calvin K. Yip, Yeong Min Yoo, Young Hyun Yoo, Seung Yong Yoon, Ken Ichi Yoshida, Tamotsu Yoshimori, Ken H. Young, Huixin Yu, Jane J. Yu, Jin Tai Yu, Jun Yu, Li Yu, W. Haung Yu, Xiao Fang Yu, Zhengping Yu, Junying Yuan, Zhi Min Yuan, Beatrice YJT Yue, Jianbo Yue, Zhenyu Yue, David N. Zacks, Eldad Zacksenhaus, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S. Zervos, Donna D. Zhang, Fan Zhang, Guo Zhang, Guo Chang Zhang, Hao Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing pu Zhang, Li Zhang, Lin Zhang, Long Zhang, Ming Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei Li Zhao, Xiaonan Zhao, Yan G. Zhao, Ying Zhao, Yongchao Zhao, Yu xia Zhao, Zhendong Zhao, Zhizhuang J. Zhao, Dexian Zheng, Xi Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu Feng Zhou, Xu jie Zhou, Hongxin Zhu, Hua Zhu, Wei Guo Zhu, Wenhua Zhu, Xiao Feng Zhu, Yuhua Zhu, Shi Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E. Zois, Teresa Zoladek, Wei Xing Zong, Antonio Zorzano, Susu M. Zughaier, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Tokyo Medical University, The Hebrew University of Jerusalem (HUJ), Mammalian Genetics Unit, Medical Research Council Harwell, University of Occupational and Environmental Health School of Medicine, Partenaires INRAE, University of Toronto, Ben-Gurion University of the Negev (BGU), University of Colorado [Boulder], Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Vienna [Vienna], Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Georgetown University, Candiolo Cancer Institute (IRCCS), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Ikerbasque - Basque Foundation for Science, Cleveland Clinic, Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Universidad de Buenos Aires (UBA), Department of Clinical Neurosciences, University College of London [London] (UCL)-Institute of Neurology, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Consiglio Nazionale delle Ricerche (CNR), Osaka University, Department of Experimental Medicine and Public Health, University of Camerino, University of Barcelona, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physics, Technical University of Denmark [Lyngby] (DTU), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre Dame de la Paix (FUNDP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Physiopathologie de la survie et de la mort cellulaire et infection virale, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Giannina Gaslini Institute, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Inner Mongolia Agricultural University (IMAU), Politecnico di Milano [Milan] (POLIMI), Department of Civil, Geological, and Mining Engineering, École Polytechnique de Montréal (EPM)-NSERC Industrial Chair on Drinking Water, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Molecular Medicine, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Department of Internal Medicine, Hospital Universitario Infanta Sofía, Celullar and Molecular Medicine, Infection bactérienne, inflammation, et carcinogenèse digestive, University of Edinburgh, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], University of Science and Technology Beijing [Beijing] (USTB), Centre for Computational and Systems Biology (COSBI), Sun Yat-Sen University [Guangzhou] (SYSU), Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), CAS Institute of Oceanology (IOCAS), Chinese Academy of Sciences [Beijing] (CAS), Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cell Biology, Physiology and Immunology, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Pisa - Università di Pisa, Dulbecco Telethon Institute/Department of Biology, Fondation de Recherche Cancer et Sang - Hôpital Kirchberg, China University of Petroleum, Unilever R&D, University of Queensland [Brisbane], University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Institute for Advanced Study [Tsinghua], Tsinghua University [Beijing] (THU), Nanayang Technological University (NTU), Nanayang Technological University, Institute of Microelectronics [Beijing] (IMETU), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Northwestern Polytechnical University [Xi'an] (NPU), University of Pennsylvania [Philadelphia], City University of Hong Kong (CityU), Department of Mathematics [Berkeley], University of California [Berkeley], University of California-University of California, ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang University, University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of New Mexico [Albuquerque], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Université Paris 1 Panthéon-Sorbonne - UFR d'Arts plastiques et sciences de l'art (UP1 UFR04), Université Paris 1 Panthéon-Sorbonne (UP1), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP), Macrophages et Développement de l’Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), This work was supported in part by the National Institutes of Health, including Public Health Service grant GM053396 to D.J.K. Due to space and other limitations, it is not possible to include all other sources of financial support., In a rapidly expanding and highly dynamic field such as autophagy, it is possible that some authors who should have been included on this article have been missed. D.J.K. extends his apologies to researchers in the field of autophagy who, due to oversight or any other reason, could not be included on this article. I also note that two of our colleagues on this manuscript have passed away: Arlette Darfeuille-Michaud and Wouter van Doorn., Life Sciences Institute [Ann Arbor, MI, USA], Laboratoire de Biogenèse Membranaire, CNRS UMR 5200, Université de Bordeaux, INRA Bordeaux Aquitaine, Villenave d'Ornon, France., Amelio, Ivano [0000-0002-9126-5391], Beale, Rupert [0000-0002-6705-8560], Floto, Andres [0000-0002-2188-5659], Frezza, Christian [0000-0002-3293-7397], Ktistakis, Nicholas [0000-0001-9397-2914], Melino, Gerry [0000-0001-9428-5972], Narita, Masashi [0000-0001-7764-577X], Rubinsztein, David [0000-0001-5002-5263], Underwood, Benjamin [0000-0003-3427-9487], Whitworth, Alex [0000-0002-1154-6629], Apollo - University of Cambridge Repository, Université Catholique de Louvain, Facultés Universitaires Notre-Dame de la Paix, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Department of Clinical and Molecular Medicine, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Sun Yat-Sen University (SYSU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), University of Minnesota [Twin Cities], Tsinghua University [Beijing], Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne - UFR d'Arts plastiques et sciences de l'art (UP1 UFR04), Université Panthéon-Sorbonne (UP1), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Necker - Enfants Malades [AP-HP], Trafic membranaire et Division cellulaire, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Klionsky, D., Abdelmohsen, K., Abe, A., Abedin, M., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C., Adams, P., Adeli, K., Adhihetty, P., Adler, S., Agam, G., Agarwal, R., Aghi, M., Agnello, M., Agostinis, P., Aguilar, P., Aguirre-Ghiso, J., Airoldi, E., Ait-Si-Ali, S., Akematsu, T., Akporiaye, E., Al-Rubeai, M., Albaiceta, G., Albanese, C., Albani, D., Albert, M., Aldudo, J., Algül, H., Alirezaei, M., Alloza, I., Almasan, A., Almonte-Beceril, M., Alnemri, E., Alonso, C., Altan-Bonnet, N., Altieri, D., Alvarez, S., Alvarez-Erviti, L., Alves, S., Amadoro, G., Amano, A., Amantini, C., Ambrosio, S., Amelio, I., Amer, A., Amessou, M., Amon, A., An, Z., Anania, F., Andersen, S., Andley, U., Andreadi, C., Andrieu-Abadie, N., Anel, A., Ann, D., Anoopkumar-Dukie, S., Antonioli, M., Aoki, H., Apostolova, N., Aquila, S., Aquilano, K., Araki, K., Arama, E., Aranda, A., Araya, J., Arcaro, A., Arias, E., Arimoto, H., Ariosa, A., Armstrong, J., Arnould, T., Arsov, I., Asanuma, K., Askanas, V., Asselin, E., Atarashi, R., Atherton, S., Atkin, J., Attardi, L., Auberger, P., Auburger, G., Aurelian, L., Autelli, R., Avagliano, L., Avantaggiati, M., Avrahami, L., Awale, S., Azad, N., Bachetti, T., Backer, J., Bae, D., Bae, J., Bae, O., Bae, S., Baehrecke, E., Baek, S., Baghdiguian, S., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bailly, Y., Balaji, K., Balduini, W., Ballabio, A., Balzan, R., Banerjee, R., Bánhegyi, G., Bao, H., Barbeau, B., Barrachina, M., Barreiro, E., Bartel, B., Bartolomé, A., Bassham, D., Bassi, M., Bast, R., Basu, A., Batista, M., Batoko, H., Battino, M., Bauckman, K., Baumgarner, B., Bayer, K., Beale, R., Beaulieu, J., Beck, G., Becker, C., Beckham, J., Bédard, P., Bednarski, P., Begley, T., Behl, C., Behrends, C., Behrens, G., Behrns, K., Bejarano, E., Belaid, A., Belleudi, F., Bénard, G., Berchem, G., Bergamaschi, D., Bergami, M., Berkhout, B., Berliocchi, L., Bernard, A., Bernard, M., Bernassola, F., Bertolotti, A., Bess, A., Besteiro, S., Bettuzzi, S., Bhalla, S., Bhattacharyya, S., Bhutia, S., Biagosch, C., Bianchi, M., Biard-Piechaczyk, M., Billes, V., Bincoletto, C., Bingol, B., Bird, S., Bitoun, M., Bjedov, I., Blackstone, C., Blanc, L., Blanco, G., Blomhoff, H., Boada-Romero, E., Böckler, S., Boes, M., Boesze-Battaglia, K., Boise, L., Bolino, A., Boman, A., Bonaldo, P., Bordi, M., Bosch, J., Botana, L., Botti, J., Bou, G., Bouché, M., Bouchecareilh, M., Boucher, M., Boulton, M., Bouret, S., Boya, P., Boyer-Guittaut, M., Bozhkov, P., Brady, N., Braga, V., Brancolini, C., Braus, G., Bravo-San Pedro, J., Brennan, L., Bresnick, E., Brest, P., Bridges, D., Bringer, M., Brini, M., Brito, G., Brodin, B., Brookes, P., Brown, E., Brown, K., Broxmeyer, H., Bruhat, A., Brum, P., Brumell, J., Brunetti-Pierri, N., Bryson-Richardson, R., Buch, S., Buchan, A., Budak, H., Bulavin, D., Bultman, S., Bultynck, G., Bumbasirevic, V., Burelle, Y., Burke, R., Burmeister, M., Bütikofer, P., Caberlotto, L., Cadwell, K., Cahova, M., Cai, D., Cai, J., Cai, Q., Calatayud, S., Camougrand, N., Campanella, M., Campbell, G., Campbell, M., Campello, S., Candau, R., Caniggia, I., Cantoni, L., Cao, L., Caplan, A., Caraglia, M., Cardinali, C., Cardoso, S., Carew, J., Carleton, L., Carlin, C., Carloni, S., Carlsson, S., Carmona-Gutierrez, D., Carneiro, L., Carnevali, O., Carra, S., Carrier, A., Carroll, B., Casas, C., Casas, J., Cassinelli, G., Castets, P., Castro-Obregon, S., Cavallini, G., Ceccherini, I., Cecconi, F., Cederbaum, A., Ceña, V., Cenci, S., Cerella, C., Cervia, D., Cetrullo, S., Chaachouay, H., Chae, H., Chagin, A., Chai, C., Chakrabarti, G., Chamilos, G., Chan, E., Chan, M., 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Shieh, Jj, Shih, Cm, Shimada, Y, Shimizu, S, Shin, Dw, Shinohara, Ml, Shintani, M, Shintani, T, Shioi, T, Shirabe, K, Shiri Sverdlov, R, Shirihai, O, Shore, Gc, Shu, Cw, Shukla, D, Sibirny, Aa, Sica, V, Sigurdson, Cj, Sigurdsson, Em, Sijwali, P, Sikorska, B, Silveira, Wa, Silvente Poirot, S, Silverman, Ga, Simak, J, Simmet, T, Simon, Ak, Simon, Hu, Simone, C, Simons, M, Simonsen, A, Singh, R, Singh, Sv, Singh, Sk, Sinha, D, Sinha, S, Sinicrope, Fa, Sirko, A, Sirohi, K, Sishi, Bj, Sittler, A, Siu, Pm, Sivridis, E, Skwarska, A, Slack, R, Slaninová, I, Slavov, N, Smaili, S, Smalley, K, Smith, Dr, Soenen, Sj, Soleimanpour, Sa, Solhaug, A, Somasundaram, K, Son, Jh, Sonawane, A, Song, C, Song, F, Song, Hk, Song, Jx, Song, W, Soo, Ky, Sood, Ak, Soong, Tw, Soontornniyomkij, V, Sorice, M, Sotgia, F, Soto Pantoja, Dr, Sotthibundhu, A, Sousa, Mj, Spaink, Hp, Span, Pn, Spang, A, Sparks, Jd, Speck, Pg, Spector, Sa, Spies, Cd, Springer, W, Clair, D, Stacchiotti, A, Staels, B, Stang, Mt, 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Taylor, Ga, Taylor, Jp, Taylor, Mj, Tchetina, Ev, Tee, Ar, Teixeira Clerc, F, Telang, S, Tencomnao, T, Teng, Bb, Teng, Rj, Terro, F, Tettamanti, G, Theiss, Al, Theron, Ae, Thomas, Kj, Thomé, Mp, Thomes, Pg, Thorburn, A, Thorner, J, Thum, T, Thumm, M, Thurston, Tl, Tian, L, Till, A, Ting, Jp, Titorenko, Vi, Toker, L, Toldo, S, Tooze, Sa, Topisirovic, I, Torgersen, Ml, Torosantucci, L, Torriglia, A, Torrisi, Mr, Tournier, C, Towns, R, Trajkovic, V, Travassos, Lh, Triola, G, Tripathi, Dn, Trisciuoglio, D, Troncoso, R, Trougakos, Ip, Truttmann, Ac, Tsai, Kj, Tschan, Mp, Tseng, Yh, Tsukuba, T, Tsung, A, Tsvetkov, A, Tu, S, Tuan, Hy, Tucci, M, Tumbarello, Da, Turk, B, Turk, V, Turner, Rf, Tveita, Aa, Tyagi, Sc, Ubukata, M, Uchiyama, Y, Udelnow, A, Ueno, T, Umekawa, M, Umemiya Shirafuji, R, Underwood, Br, Ungermann, C, Ureshino, Rp, Ushioda, R, Uversky, Vn, Uzcátegui, Nl, Vaccari, T, Vaccaro, Mi, Váchová, L, Vakifahmetoglu Norberg, H, Valdor, R, Valente, Em, Vallette, F, Valverde, Am, Van den Berghe, G, Van Den Bosch, L, van den Brink, Gr, van der Goot, Fg, van der Klei, Ij, van der Laan, Lj, van Doorn, Wg, van Egmond, M, van Golen, Kl, Van Kaer, L, van Lookeren Campagne, M, Vandenabeele, P, Vandenberghe, W, Vanhorebeek, I, Varela Nieto, I, Vasconcelos, Mh, Vasko, R, Vavvas, Dg, Vega Naredo, I, Velasco, G, Velentzas, Ad, Velentzas, Pd, Vellai, T, Vellenga, E, Vendelbo, Mh, Venkatachalam, K, Ventura, N, Ventura, S, Veras, P, Verdier, M, Vertessy, Bg, Viale, A, Vidal, M, Vieira, H, Vierstra, Rd, Vigneswaran, N, Vij, N, Vila, M, Villar, M, Villar, Vh, Villarroya, J, Vindis, C, Viola, G, Viscomi, Mt, Vitale, G, Vogl, Dt, Voitsekhovskaja, Ov, von Haefen, C, von Schwarzenberg, K, Voth, De, Vouret Craviari, V, Vuori, K, Vyas, Jm, Waeber, C, Walker, Cl, Walker, Mj, Walter, J, Wan, L, Wan, X, Wang, B, Wang, C, Wang, Cy, Wang, D, Wang, F, Wang, G, Wang, Hj, Wang, H, Wang, Hg, Wang, Hd, Wang, J, Wang, M, Wang, Mq, Wang, Py, Wang, P, Wang, Rc, Wang, S, Wang, Tf, Wang, X, Wang, Xj, Wang, Xw, Wang, Y, Wang, Yj, Wang, Yt, Wang, Zn, Wappner, P, Ward, C, Ward, Dm, Warnes, G, Watada, H, Watanabe, Y, Watase, K, Weaver, Te, Weekes, Cd, Wei, J, Weide, T, Weihl, Cc, Weindl, G, Weis, Sn, Wen, L, Wen, X, Wen, Y, Westermann, B, Weyand, Cm, White, Ar, White, E, Whitton, Jl, Whitworth, Aj, Wiels, J, Wild, F, Wildenberg, Me, Wileman, T, Wilkinson, D, Wilkinson, S, Willbold, D, Williams, C, Williams, K, Williamson, Pr, Winklhofer, Kf, Witkin, S, Wohlgemuth, Se, Wollert, T, Wolvetang, Ej, Wong, E, Wong, Gw, Wong, Rw, Wong, Vk, Woodcock, Ea, Wright, Kl, Wu, C, Wu, D, Wu, G, Wu, J, Wu, M, Wu, S, Wu, Wk, Wu, Y, Wu, Z, Xavier, Cp, Xavier, Rj, Xia, Gx, Xia, T, Xia, W, Xia, Y, Xiao, H, Xiao, J, Xiao, S, Xiao, W, Xie, Cm, Xie, Z, Xilouri, M, Xiong, Y, Xu, C, Xu, F, Xu, H, Xu, J, Xu, L, Xu, X, Xu, Y, Xu, Zx, Xu, Z, Xue, Y, Yamada, T, Yamamoto, A, Yamanaka, K, Yamashina, S, Yamashiro, S, Yan, B, Yan, X, Yan, Z, Yanagi, Y, Yang, D, Yang, Jm, Yang, L, Yang, M, Yang, Pm, Yang, P, Yang, Q, Yang, W, Yang, Wy, Yang, X, Yang, Y, Yang, Z, Yao, Mc, Yao, Pj, Yao, X, Yao, Z, Yasui, L, Ye, M, Yedvobnick, B, Yeganeh, B, Yeh, E, Yeyati, Pl, Yi, F, Yi, L, Yin, Xm, Yip, Ck, Yoo, Ym, Yoo, Yh, Yoon, Sy, Yoshida, Ki, Yoshimori, T, Young, Kh, Yu, H, Yu, Jj, Yu, Jt, Yu, J, Yu, L, Yu, Wh, Yu, Xf, Yu, Z, Yuan, J, Yuan, Zm, Yue, By, Yue, J, Yue, Z, Zacks, Dn, Zacksenhaus, E, Zaffaroni, N, Zaglia, T, Zakeri, Z, Zecchini, V, Zeng, J, Zeng, M, Zeng, Q, Zervos, A, Zhang, Dd, Zhang, F, Zhang, G, Zhang, Gc, Zhang, H, Zhang, J, Zhang, Jp, Zhang, L, Zhang, My, Zhang, X, Zhang, Xd, Zhang, Y, Zhao, M, Zhao, Wl, Zhao, X, Zhao, Yg, Zhao, Y, Zhao, Yx, Zhao, Z, Zhao, Zj, Zheng, D, Zheng, Xl, Zheng, X, Zhivotovsky, B, Zhong, Q, Zhou, Gz, Zhou, G, Zhou, H, Zhou, Sf, Zhou, Xj, Zhu, H, Zhu, Wg, Zhu, W, Zhu, Xf, Zhu, Y, Zhuang, Sm, Zhuang, X, Ziparo, E, Zois, Ce, Zoladek, T, Zong, Wx, Zorzano, A, Zughaier, Sm, AII - Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, Other departments, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, ANS - Cellular & Molecular Mechanisms, Cell Biology and Histology, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Daniel J Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M Adam, Peter D Adam, Khosrow Adeli, Peter J Adhihetty, Sharon G Adler, Galila Agam, Rajesh Agarwal, Manish K Aghi, Maria Agnello, Patrizia Agostini, Patricia V Aguilar, Julio Aguirre-Ghiso, Edoardo M Airoldi, Slimane Ait-Si-Ali, Takahiko Akematsu, Emmanuel T Akporiaye, Mohamed Al-Rubeai, Guillermo M Albaiceta, Chris Albanese, Diego Albani, Matthew L Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte-Beceril, Emad S Alnemri, Covadonga Alonso, Nihal Altan-Bonnet, Dario C Altieri, Silvia Alvarez, Lydia Alvarez- Erviti, Sandro Alve, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A Anania, Stig U Andersen, Usha P Andley, Catherine K Andreadi, Nathalie Andrieu- Abadie, Alberto Anel, David K Ann, Shailendra Anoopkumar-Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Aria, Hirokazu Arimoto, Aileen R Ariosa, Jane L Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askana, Eric Asselin, Ryuichiro Atarashi, Sally S Atherton, Julie D Atkin, Laura D Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M Backer, Dong- Hun Bae, Jae-sung Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Seung-Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska-Zadworna, Hua Bai, Jie Bai, Xue-Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C Bassham, Maria Teresa Bassi, Robert C Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L Baumgarner, K Ulrich Bayer, Rupert Beale, Jean-François Beaulieu, George R. Beck Jr, Christoph Becker, J David Beckham, Pierre-André Bédard, Patrick J Bednarski, Thomas J Begley, Christian Behl, Christian Behrend, Georg MN Behren, Kevin E Behrn, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S Be, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard-Piechaczyk, Viktor Bille, Claudia Bincoletto, Baris Bingol, Sara W Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A Blanco, Heidi Kiil Blomhoff, Emilio Boada-Romero, Stefan Böckler, Marianne Boe, Kathleen Boesze-Battaglia, Lawrence H Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie- Josée Boucher, Michael E Boulton, Sebastien G Bouret, Patricia Boya, Michaël Boyer-Guittaut, Peter V Bozhkov, Nathan Brady, Vania MM Braga, Claudio Brancolini, Gerhard H Brau, José M Bravo-San Pedro, Lisa A Brennan, Emery H Bresnick, Patrick Brest, Dave Bridge, MarieAgnès Bringer, Marisa Brini, Glauber C Brito, Bertha Brodin, Paul S Brooke, Eric J Brown, Karen Brown, Hal E Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H Brumell, Nicola Brunetti-Pierri, Robert J Bryson-Richardson, Shilpa Buch, Alastair M Buchan, Hikmet Budak, Dmitry V Bulavin, Scott J Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S Carew, Laura A Carleton, Cathleen R Carlin, Silvia Carloni, Sven R Carlsson, Didac Carmona-Gutierrez, Leticia AM Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casa, Josefina Casa, Giuliana Cassinelli, Perrine Castet, Susana Castro-Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, Silvia Cetrullo, Hassan Chaachouay, Han-Jung Chae, Andrei S Chagin, Chee-Yin Chai, Gopal Chakrabarti, Georgios Chamilo, Edmond YW Chan, Matthew TV Chan, Dhyan Chandra, Pallavi Chandra, Chih-Peng Chang, Raymond Chuen-Chung Chang, Ta Yuan Chang, John C Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E Cheetham, Rajkumar Cheluvappa, Chun-Jung Chen, Gang Chen, Guang-Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W Chen, Jian-Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang- Der Chen, Si Chen, Steve S-L Chen, Wei Chen, 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Vincent CO Njar, Takeshi Noda, Angelika A Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B O'Donnell, Tracey O'Donovan, Peter J O'Dwyer, Ina Oehme, Clara L Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J O'Rourke, Helena Orozco, Angel L Ortega, Elena Ortona, Laura D Osellame, Junko Oshima, Shigeru Oshima, Heinz D Osiewacz, Takanobu Otomo, Kinya Otsu, Jing-hsiung James Ou, Tiago F Outeiro, Dong-yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A Ozbun, P Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Page, Ugo Pagnini, Beata Pajak, Stephen C Pak, Karolina Pakos-Zebrucka, Nazzy Pakpour, Zdena Palková, Francesca Palladino, Kathrin Pallauf, Nicolas Pallet, Marta Palmieri, Søren R Paludan, Camilla Palumbo, Silvia Palumbo, Olatz Pampliega, Hongming Pan, Wei Pan, Theocharis Panaretaki, Aseem Pandey, Areti Pantazopoulou, Zuzana Papackova, Daniela L Papademetrio, Issidora Papassideri, Alessio Papini, Nirmala Parajuli, Julian Pardo, Vrajesh V Parekh, Giancarlo Parenti, Jong-In Park, Junsoo Park, Ohkmae K Park, Roy Parker, Rosanna Parlato, Jan B Pary, Katherine R Parzych, Jean-Max Pasquet, Benoit Pasquier, Kishore BS Pasumarthi, Daniel Patschan, Cam Patterson, Sophie Pattingre, Scott Pattison, Arnim Pause, Hermann Pavenstädt, Flaminia Pavone, Zully Pedrozo, Fernando J Peña, Miguel A Peñalva, Mario Pende, Jianxin Peng, Fabio Penna, Josef M Penninger, Anna Pensalfini, Salvatore Pepe, Gustavo JS Pereira, Paulo C Pereira, Verónica Pérez-de la Cruz, María Esther Pérez-Pérez, Diego Pérez-Rodríguez, Dolores Pérez-Sala, Celine Perier, Andras Perl, David H Perlmutter, Ida Perrotta, Shazib 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Rohrer, Davide Romanelli, Luigina Romani, Patricia Silvia Romano, M Isabel G Roncero, Jose Luis Rosa, Alicia Rosello, Kirill V Rosen, Philip Rosenstiel, Magdalena Rost-Roszkowska, Kevin A Roth, Gael Roué, Mustapha Roui, Kasper M Rouschop, Daniel T Ruan, Diego Ruano, David C Rubinsztein, Edmund B Rucker III, Assaf Rudich, Emil Rudolf, Ruediger Rudolf, Markus A Ruegg, Carmen Ruiz-Roldan, Avnika Ashok Ruparelia, Paola Rusmini, David W Ru, Gian Luigi Russo, Giuseppe Russo, Rossella Russo, Tor Erik Rusten, Victoria Ryabovol, Kevin M Ryan, Stefan W Ryter, David M Sabatini, Michael Sacher, Carsten Sachse, Michael N Sack, Junichi Sadoshima, Paul Saftig, Ronit Sagi-Eisenberg, Sumit Sahni, Pothana Saikumar, Tsunenori Saito, Tatsuya Saitoh, Koichi Sakakura, Machiko Sakoh-Nakatogawa, Yasuhito Sakuraba, María Salazar-Roa, Paolo Salomoni, Ashok K Saluja, Paul M Salvaterra, Rosa Salvioli, Afshin Samali, Anthony MJ Sanchez, José A Sánchez-Alcázar, Ricardo Sanchez-Prieto, Marco Sandri, Miguel A Sanjuan, Stefano Santaguida, Laura Santambrogio, Giorgio Santoni, Claudia Nunes dos Santo, Shweta Saran, Marco Sardiello, Graeme Sargent, Pallabi Sarkar, Sovan Sarkar, Maria Rosa Sarria, Minnie M Sarwal, Chihiro Sasakawa, Motoko Sasaki, Miklos Sa, Ken Sato, Miyuki Sato, Joseph Satriano, Niramol Savaraj, Svetlana Saveljeva, Liliana Schaefer, Ulrich E Schaible, Michael Scharl, Hermann M Schatzl, Randy Schekman, Wiep Scheper, Alfonso Schiavi, Hyman M Schipper, Hana Schmeisser, Jens Schmidt, Ingo Schmitz, Bianca E Schneider, E Marion Schneider, Jaime L Schneider, Eric A Schon, Miriam J Schönenberger, Axel H Schönthal, Daniel F Schorderet, Bernd Schröder, Sebastian Schuck, Ryan J Schulze, Melanie Schwarten, Thomas L Schwarz, Sebastiano Sciarretta, Kathleen Scotto, A Ivana Scovassi, Robert A Screaton, Mark Screen, Hugo Seca, Simon Sedej, Laura Segatori, Nava Segev, Per O Seglen, Jose M Seguí- Simarro, Juan Segura-Aguilar, Ekihiro Seki, Iban Seiliez, Christian Sell, Clay F Semenkovich, Gregg 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Shrawan K Singh, Debasish Sinha, Sangita Sinha, Frank A Sinicrope, Agnieszka Sirko, Kapil Sirohi, Balindiwe JN Sishi, Annie Sittler, Parco M Siu, Efthimios Sivridi, Anna Skwarska, Ruth Slack, Iva Slaninová, Nikolai Slavov, Soraya S Smaili, Keiran SM Smalley, Duncan R Smith, Stefaan J Soenen, Scott A Soleimanpour, Anita Solhaug, Kumaravel Somasundaram, Jin H Son, Avinash Sonawane, Chunjuan Song, Fuyong Song, Hyun Kyu Song, Ju-Xian Song, Wei Song, Kai Y Soo, Anil K Sood, Tuck Wah Soong, Virawudh Soontornniyomkij, Maurizio Sorice, Federica Sotgia, David R Soto-Pantoja, Areechun Sotthibundhu, Maria João Sousa, Herman P Spaink, Paul N Span, Anne Spang, Janet D Spark, Peter G Speck, Stephen A Spector, Claudia D Spie, Wolfdieter Springer, Daret St Clair, Alessandra Stacchiotti, Bart Stael, Michael T Stang, Daniel T Starczynowski, Petro Starokadomskyy, Clemens Steegborn, John W Steele, Leonidas Stefani, Joan Steffan, Christine M Stellrecht, Harald Stenmark, Tomasz M Stepkowski, Stęphan T 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Tanaka, Masaki Tanaka, Daolin Tang, Dingzhong Tang, Guomei Tang, Isei Tanida, Kunikazu Tanji, Bakhos A Tannou, Jose A Tapia, Inmaculada Tasset-Cueva, Marc Tatar, Iman Tavassoly, Nektarios Tavernaraki, Allen Taylor, Graham S Taylor, Gregory A Taylor, J Paul Taylor, Mark J Taylor, Elena V Tchetina, Andrew R Tee, Fatima Teixeira-Clerc, Sucheta Telang, Tewin Tencomnao, Ba-Bie Teng, Ru-Jeng Teng, Faraj Terro, Gianluca Tettamanti, Arianne L Thei, Anne E Theron, Kelly Jean Thoma, Marcos P Thomé, Paul G Thome, Andrew Thorburn, Jeremy Thorner, Thomas Thum, Michael Thumm, Teresa LM Thurston, Ling Tian, Andreas Till, Jenny Pan-yun Ting, Vladimir I Titorenko, Lilach Toker, Stefano Toldo, Sharon A Tooze, Ivan Topisirovic, Maria Lyngaas Torgersen, Liliana Torosantucci, Alicia Torriglia, Maria Rosaria Torrisi, Cathy Tournier, Roberto Town, Vladimir Trajkovic, Leonardo H Travasso, Gemma Triola, Durga Nand Tripathi, Daniela Trisciuoglio, Rodrigo Troncoso, Ioannis P Trougako, Anita C Truttmann, Kuen-Jer Tsai, Mario P Tschan, Yi-Hsin Tseng, Takayuki Tsukuba, Allan Tsung, Andrey S Tsvetkov, Shuiping Tu, Hsing-Yu Tuan, Marco Tucci, David A Tumbarello, Boris Turk, Vito Turk, Robin FB Turner, Anders A Tveita, Suresh C Tyagi, Makoto Ubukata, Yasuo Uchiyama, Andrej Udelnow, Takashi Ueno, Midori Umekawa, Rika Umemiya-Shirafuji, Benjamin R Underwood, Christian Ungermann, Rodrigo P. Ureshino, Ryo Ushioda, Vladimir N Uversky, Néstor L Uzcátegui, Thomas Vaccari, Maria I Vaccaro, Libuše Váchová, Helin Vakifahmetoglu-Norberg, Rut Valdor, Enza Maria Valente, Francois Vallette, Angela M Valverde, Greet Van den Berghe, Ludo Van Den Bosch, Gijs R van den Brink, F Gisou van der Goot, Ida J van der Klei, Luc JW van der Laan, Wouter G van Doorn, Marjolein van Egmond, Kenneth L van Golen, Luc Van Kaer, Menno van Lookeren Campagne, Peter Vandenabeele, Wim Vandenberghe, Ilse Vanhorebeek, Isabel Varela-Nieto, M Helena Vasconcelo, Radovan Vasko, Demetrios G Vavva, Ignacio Vega- Naredo, Guillermo Velasco, Athanassios D Velentza, Panagiotis D Velentza, Tibor Vellai, Edo Vellenga, Mikkel Holm Vendelbo, Kartik Venkatachalam, Natascia Ventura, Salvador Ventura, Patrícia ST Vera, Mireille Verdier, Beata G Vertessy, Andrea Viale, Michel Vidal, Helena LA Vieira, Richard D Vierstra, Nadarajah Vigneswaran, Neeraj Vij, Miquel Vila, Margarita Villar, Victor H Villar, Joan Villarroya, Cécile Vindi, Giampietro Viola, Maria Teresa Viscomi, Giovanni Vitale, Dan T Vogl, Olga V Voitsekhovskaja, Clarissa von Haefen, Karin von Schwarzenberg, Daniel E Voth, Valérie Vouret-Craviari, Kristina Vuori, Jatin M Vya, Christian Waeber, Cheryl Lyn Walker, Mark J Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao-Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai-jie Wang, Haichao Wang, Hong-Gang Wang, Hongmin Wang, Horng-Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei-Qing Wang, Pei-Yu Wang, Peng Wang, Richard C Wang, Shuo Wang, Ting-Fang Wang, Xian Wang, Xiao-jia Wang, Xiao-Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying-Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi-Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warne, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=kaup20 Download by: [Alma Mater Studiorum - Università di Bologna] Date: 23 September 2016, At: 06:43 Weaver, Colin D Weeke, Jiwu Wei, Thomas Weide, Conrad C Weihl, Günther Weindl, Simone Nardin Wei, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M Weyand, Anthony R White, Eileen White, J Lindsay Whitton, Alexander J Whitworth, Joëlle Wiel, Franziska Wild, Manon E Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris William, Katherine William, Peter R Williamson, Konstanze F Winklhofer, Steven S Witkin, Stephanie E Wohlgemuth, Thomas Wollert, Ernst J Wolvetang, Esther Wong, G William Wong, Richard W Wong, Vincent Kam Wai Wong, Elizabeth A Woodcock, Karen L Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William KK Wu, Yaohua Wu, Zhenlong Wu, Cristina PR Xavier, Ramnik J Xavier, Gui-Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan-Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi-Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun-Sheng Yang, Jin-Ming Yang, Liu Yang, Minghua Yang, Pei-Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng-Chao Yao, Pamela J Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S Yeh, Patricia L Yeyati, Fan Yi, Long Yi, Xiao-Ming Yin, Calvin K Yip, Yeong-Min Yoo, Young Hyun Yoo, Seung-Yong Yoon, Ken-Ichi Yoshida, Tamotsu Yoshimori, Ken H Young, Huixin Yu, Jane J Yu, Jin-Tai Yu, Jun Yu, Li Yu, W Haung Yu, Xiao-Fang Yu, Zhengping Yu, Junying Yuan, Zhi-Min Yuan, Beatrice YJT Yue, Jianbo Yue, Zhenyu Yue, David N Zack, Eldad Zacksenhau, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S Zervo, Donna D Zhang, Fan Zhang, Guo Zhang, Guo-Chang Zhang, Hao Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing-pu Zhang, Li Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei-Li Zhao, Xiaonan Zhao, Yan G Zhao, Ying Zhao, Yongchao Zhao, Yu-xia Zhao, Zhendong Zhao, Zhizhuang J Zhao, Dexian Zheng, Xi-Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang-Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu-Feng Zhou, Xu-jie Zhou, Hongxin Zhu, Hua Zhu, Wei- Guo Zhu, Wenhua Zhu, Xiao-Feng Zhu, Yuhua Zhu, Shi-Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E Zoi, Teresa Zoladek, Wei-Xing Zong, and Antonio Zorzano & Susu M Zughaier
Subjects: [SDV]Life Sciences [q-bio], autophagosome, Review Article, ddc:616.07, stress, stre, LC3, MESH: Animals, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Settore BIO/06 - Anatomia Comparata E Citologia, chaperone-mediated autophagy, ComputingMilieux_MISCELLANEOUS, Settore BIO/11, Pharmacology. Therapy, Settore BIO/13, standards [Biological Assay], autolysosome, MESH: Autophagy*/physiology, lysosome, methods [Biological Assay], Biological Assay, Settore BIO/17 - ISTOLOGIA, Erratum, Human, Biochemistry & Molecular Biology, Settore BIO/06, physiology [Autophagy], Chaperonemediated autophagy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, NO, autophagy, guidelines, molecular biology, ultrastructure, flux, macroautophagy, phagophore, vacuole, MESH: Biological Assay/methods, MESH: Computer Simulation, ddc:570, Autolysosome, Autophagosome, Chaperonemediated autophagy, Flux, LC3, Lysosome, Macroautophagy, Phagophore, Stress, Vacuole, Autophagy, Animals, Humans, Computer Simulation, Settore BIO/10, ddc:612, Biology, MESH: Humans, Animal, 0601 Biochemistry And Cell Biology, MESH: Biological Assay/standards, Human medicine
Abstract: Seuls les 100 premiers auteurs dont les auteurs INRA ont été entrés dans la notice. La liste complète des auteurs et de leurs affiliations est accessible sur la publication.; International audience; In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
Published: 2016
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67. Gankyrin promotes tumor growth and metastasis through activation of IL-6/STAT3 signaling in human cholangiocarcinoma

Author: Yingjian Liang, Yuejin Li, Nishant Bhatta, Zhaoyang Lu, Shuai Li, Shu-Yi Qi, Xiang Fang, Xiaohe Luo, Shangha Pan, Ruipeng Song, Tiemin Pei, Lianxin Liu, Xuehui Hong, Xuan Song, Tongsen Zheng, Changming Xie, Jiabei Wang, Jiaren Liu, Hongchi Jiang, Boshi Sun, and Dalong Yin
Subjects: STAT3 Transcription Factor, Proteasome Endopeptidase Complex, Small interfering RNA, Gankyrin, medicine.disease_cause, Retinoblastoma Protein, Metastasis, Cholangiocarcinoma, Cell Movement, Predictive Value of Tests, Proto-Oncogene Proteins, parasitic diseases, medicine, Humans, Neoplasm Invasiveness, STAT3, Gene knockdown, Hepatology, biology, Interleukin-6, Cell growth, Cell Cycle Checkpoints, Prognosis, medicine.disease, Gene Expression Regulation, Neoplastic, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, biology.protein, STAT protein, Cancer research, Carcinogenesis, Signal Transduction
Abstract: Although gankyrin is involved in the tumorigenicity and metastasis of some malignancies, the role of gankyrin in cholangiocarcinoma (CCA) is unclear. In this study we investigated the expression of gankyrin in human CCA tissues and cell lines. The effects of gankyrin on CCA tumor growth and metastasis were determined both in vivo and in vitro. The results showed that gankyrin was overexpressed in CCA tissues and cell lines. Gankyrin expression was associated with CCA histological differentiation, TNM stage, and metastasis. The multivariate Cox analysis revealed that gankyrin was an independent prognostic indicator for overall survival. Gankyrin overexpression promoted CCA cell proliferation, migration, and invasion, while gankyrin knockdown inhibited CCA tumor growth, metastasis, and induced Rb-dependent senescence and G1 phase cell cycle arrest. Gankyrin increased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and promoted the nuclear translocation of p-STAT3. Suppression of STAT3 signaling by small interfering RNA (siRNA) or STAT3 inhibitor interfered with gankyrin-mediated carcinogenesis and metastasis, while interleukin (IL)-6, a known upstream activator of STAT3, could restore the proliferation and migration of gankyrin-silenced CCA cells. The IL-6 level was decreased by gankyrin knockdown, while increased by gankyrin overexpression. Gankyrin regulated IL-6 expression by way of facilitating the phosphorylation of Rb; meanwhile, rIL-6 treatment increased the expression of gankyrin, suggesting that IL-6 was regulated by a positive feedback loop involving gankyrin in CCA. In the xenograft experiments, gankyrin overexpression accelerated tumor formation and increased tumor weight, whereas gankyrin knockdown showed the opposite effects. The in vivo spontaneous metastasis assay revealed that gankyrin promoted CCA metastasis through IL-6/STAT3 signaling pathway. Conclusion: Gankyrin is crucial for CCA carcinogenesis and metastasis by activating IL-6/STAT3 signaling pathway through down-regulating Rb protein. (Hepatology 2014;59:935–946)
Published: 2014
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68. Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells

Author: Haiquan Qiao, Xueying Sun, Zheng Wei, Hongchi Jiang, Bing Liu, Bo Tang, and Xuesong Dong
Subjects: Male, Vascular smooth muscle, Physiology, Aorta, Thoracic, Apoptosis, Muscle, Smooth, Vascular, Restenosis, Proliferating Cell Nuclear Antigen, Autophagy, Animals, Medicine, Cyclin D1, Everolimus, RNA, Small Interfering, Rats, Wistar, Cells, Cultured, Cell Proliferation, Sirolimus, business.industry, Ribosomal Protein S6 Kinases, TOR Serine-Threonine Kinases, Intracellular Signaling Peptides and Proteins, Cell cycle, Phosphoproteins, medicine.disease, Immunology, Cancer research, Vascular Resistance, Carrier Proteins, Cardiology and Cardiovascular Medicine, business, Cyclin-Dependent Kinase Inhibitor p27, Immunosuppressive Agents, medicine.drug
Abstract: Objective: The present study aims to investigate the underlying mechanisms accounting for the activities of everolimus to inhibit the growth of vascular smooth muscle cells (VSMCs), which contributes to restenosis. Methods: Primary VSMCs were cultured in media containing smooth muscle growth supplements and incubated with testing agents. Cell proliferation, cell cycle distribution, apoptosis and autophagy, and the key molecules involved, were examined. Results: Everolimus inhibited the proliferation of VSMCs by inhibiting the activation of ribosomal protein S6 kinase and phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, and downregulating proliferating cellular nuclear antigen. Everolimus induced cell cycle arrest at the G1 phase by downregulating cyclin D1 and upregulating p27, and increased apoptosis by downregulating Bcl-2, upregulating Bad and activating capsase-3 and poly ADP ribose polymerase. Everolimus enhanced autophagy by increasing the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II, and upregulating Beclin 1. Specific autophagy inhibitors, 3-methyladenine and bafilomycin A1, significantly attenuated the inhibition of cell proliferation, the increased apoptosis and the altered expression of the above key proteins induced by everolimus. Conclusions: Enhanced autophagy by everolimus contributes to its antirestenotic activity and its abilities to inhibit cell proliferation and to induce apoptosis of VSMCs.
Published: 2014
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69. PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis

Author: Shu-Yi Qi, Huiwen Song, Yingjian Liang, Ruipeng Song, Zhaoyang Lu, Tongsen Zheng, Zhiyong Zhang, Jiabei Wang, Xuan Song, Hongchi Jiang, Xuehui Hong, and Lianxin Liu
Subjects: Male, Carcinoma, Hepatocellular, Heterogeneous nuclear ribonucleoprotein, RNA Splicing, Phosphatase, Glucosephosphate Dehydrogenase, Biology, Heterogeneous-Nuclear Ribonucleoprotein K, Pentose Phosphate Pathway, Mice, chemistry.chemical_compound, Liver Neoplasms, Experimental, Proto-Oncogene Proteins, RNA Precursors, Animals, Humans, Tensin, PTEN, Phosphorylation, Protein kinase B, Mice, Knockout, Mice, Inbred BALB C, Gene knockdown, PTEN Phosphohydrolase, Gastroenterology, Glucose, Glycogen Synthase, Ribonucleoproteins, chemistry, Cancer research, biology.protein, Nicotinamide adenine dinucleotide phosphate
Abstract: Background Mounting epidemiological evidence supports a role for phosphatase and tensin homologue (PTEN)-T cell leukaemia 1 (Tcl1) signalling deregulation in hepatocarcinogenesis. Objective To determine the molecular and biochemical mechanisms by which the PTEN/Tcl1 axis regulates the pentose phosphate pathway (PPP) in hepatocellular carcinoma (HCC). Methods We compared levels of PTEN and glucose-6-phosphate dehydrogenase (G6PD) mRNA in human HCC and healthy liver tissue. We measured PPP flux, glucose consumption, lactate production, nicotinamide adenine dinucleotide phosphate (NADPH) levels and lipid accumulation. We investigated the PTEN/Tcl1 axis using molecular biology, biochemistry and mass spectrometry analysis. We assessed proliferation, apoptosis and senescence in cultured cells, and tumour formation in mice. Results We showed that PTEN inhibited the PPP pathway in human liver tumours. Through the PPP, PTEN suppressed glucose consumption and biosynthesis. Mechanistically, the PTEN protein bound to G6PD, the first and rate-limiting enzyme of the PPP and prevented the formation of the active G6PD dimer. Tcl1, a coactivator for Akt, reversed the effects of PTEN on biosynthesis. Tcl1 promoted G6PD activity and also increased G6PD pre-mRNA splicing and protein expression in a heterogeneous nuclear ribonucleoprotein (hnRNPK)-dependent manner. PTEN also formed a complex with hnRNPK, which inhibited G6PD pre-mRNA splicing. Moreover, PTEN inactivated Tcl1 via glycogen synthase kinase-3β (GSK3β)-mediated phosphorylation. Importantly, Tcl1 knockdown enhanced the sensitivity of HCC to sorafenib, whereas G6PD knockdown inhibited hepatocarcinogenesis. Conclusions These results establish the counteraction between PTEN and Tcl1 as a key mechanism that regulates the PPP and suggest that targeting the PTEN/Tcl1/hnRNPK/G6PD axis could open up possibilities for therapeutic intervention and improve the prognosis of patients with HCC.
Published: 2013
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70. Up-regulation of survivin by AKT and hypoxia-inducible factor 1α contributes to cisplatin resistance in gastric cancer

Author: Xiaolong Wang, Haiquan Qiao, Xueying Sun, Hongchi Jiang, Lele Lin, Xian Jiang, Bo Sun, Xuesong Dong, Zheng Wei, Bo Zhai, Geoffrey W. Krissansen, Xue-Pu Sun, and Qiang Zhang
Subjects: Male, inorganic chemicals, Survivin, Blotting, Western, Mice, Nude, Antineoplastic Agents, Apoptosis, Real-Time Polymerase Chain Reaction, Biochemistry, Inhibitor of Apoptosis Proteins, Small hairpin RNA, Mice, Stomach Neoplasms, Tumor Cells, Cultured, medicine, Animals, Humans, RNA, Messenger, neoplasms, Molecular Biology, Protein kinase B, Cell Proliferation, Cisplatin, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, Chemistry, Cell Biology, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular biology, female genital diseases and pregnancy complications, Hypoxia-inducible factors, Drug Resistance, Neoplasm, Cancer cell, Cancer research, Proto-Oncogene Proteins c-akt, medicine.drug
Abstract: This study investigated the contribution of survivin and its upstream regulators, AKT and hypoxia-inducible factor 1α (HIF-1α), to the resistance of gastric cancer cells to cisplatin (CDDP). We found that over-expression of survivin increased the resistance of SGC7901 and BGC823 gastric cancer cells to CDDP. Its over-expression abrogated CDDP-induced inhibition of cell proliferation and CDDP-induced cell apoptosis. In contrast, down-regulation of survivin expression using small hairpin RNA (shRNA) vectors and the small-molecule inhibitor YM155, or inhibition of survivin function using a recombinant cell-permeable dominant-negative survivin protein (dNSur9), promoted CDDP-induced apoptosis. CDDP-resistant sub-lines generated from the parental SGC7901 and BGC823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF-1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (pAKT). Specific inhibition of AKT reduced the expression of HIF-1α and survivin, whereas specific inhibition or depletion of HIF-1α reduced survivin expression but had no effect on the expression of phosphorylated AKT. The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF-1α enhanced the sensitivity of CDDP-resistant cells to CDDP. Specific inhibition of survivin, AKT and HIF-1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up-regulation of survivin by AKT and HIF-1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.
Published: 2013
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71. Protective effects of hydroxytyrosol on liver ischemia/reperfusion injury in mice

Author: Huayang Pan, Jizhou Wang, Shangha Pan, Xueying Sun, Hongchi Jiang, Kai Kang, Bei Sun, Lianxin Liu, Dawei Wang, and Yong Ma
Subjects: Male, Necrosis, Cell Survival, Chemokine CXCL2, Apoptosis, Pharmacology, medicine.disease_cause, Antioxidants, Superoxide dismutase, Mice, chemistry.chemical_compound, Malondialdehyde, In Situ Nick-End Labeling, medicine, Animals, chemistry.chemical_classification, Mice, Inbred BALB C, Reactive oxygen species, biology, Interleukin-6, Superoxide Dismutase, Tumor Necrosis Factor-alpha, Phenylethyl Alcohol, Catalase, medicine.disease, Disease Models, Animal, Oxidative Stress, Liver, chemistry, Biochemistry, Reperfusion Injury, Hepatocytes, biology.protein, Hydroxytyrosol, medicine.symptom, Reactive Oxygen Species, Reperfusion injury, Oxidative stress, Food Science, Biotechnology
Abstract: Scope Hydroxytyrosol (HT), a main phenolic compound in olive oil, has been proved to be a potent antioxidant and has beneficial effects on health. However, the effect of HT on oxidative liver damage, as seen in ischemia/reperfusion (I/R) injury, is unknown. Here, we examined whether HT could protect liver against I/R injury. Methods and results By using a mouse model, we found that HT administration protects against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and less parenchymal necrosis and apoptosis. Serum levels of tumor necrosis factor-α, interleukin-6, macrophage inflammatory protein 2, as well as reactive oxygen species (ROS) content in liver tissues, were all decreased by HT, the latter correlated with the reduction of hepatic malondialdehyde (an index of oxidative stress) content and increased activities and expressions of liver antioxidant enzymes superoxide dismutase and catalase. The protective effect was also seen in isolated hepatocytes anoxia/reoxygenation assay. Conclusion HT exerts protective effects against hepatic I/R injury in mice, which might be associated with its anti-oxidative, anti-inflammatory, and anti-apoptotic properties. HT may be an effective hepatoprotective agent and a promising candidate for the treatment of liver I/R injury.
Published: 2013
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72. Reduction of hepatic fibrosis by overexpression of von Hippel–Lindau protein in experimental models of chronic liver disease

Author: Shangha Pan, Hui Miao, Yong Ma, Lianxin Liu, Jizhou Wang, Ruipeng Song, Dawei Wang, Xueying Sun, Shugeng Zhang, Hongchi Jiang, Baolei Zhao, Zhilin Xu, Pei Tian, Xuan Song, and Zhaoyang Lu
Subjects: 0301 basic medicine, Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, endocrine system diseases, Chronic liver disease, urologic and male genital diseases, Article, End Stage Liver Disease, 03 medical and health sciences, Cholestasis, Fibrosis, medicine, Basic Helix-Loop-Helix Transcription Factors, Gene silencing, Humans, Aged, Multidisciplinary, business.industry, Fatty liver, Hepatitis C, Middle Aged, medicine.disease, Hypoxia-Inducible Factor 1, alpha Subunit, female genital diseases and pregnancy complications, Cell Hypoxia, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Von Hippel-Lindau Tumor Suppressor Protein, Hepatic stellate cell, Female, Hepatic fibrosis, business, Fatty Liver, Alcoholic
Abstract: Hypoxia-inducible factor (HIF)-1α and HIF-2α play an important role in liver fibrosis. von Hippel–Lindau protein (VHL), a key mediator of HIF-α, regulates fibrosis in an organ- and cell-specific way. In this study, human liver samples were collected from hepatitis C-, alcoholic-, and cholestatic-associated fibrotic and healthy individuals. Two mouse models of liver fibrosis were established: bile duct ligation and carbon tetrachloride injection. We constructed adenovirus vectors to overexpress VHL, normoxia-active HIF-α, and lentiviral vectors to silence HIF-α. The results showed that liver sections from fibrosis patients had a lower level of VHL and higher levels of HIF-1α and HIF-2α compared with healthy sections, a finding which was confirmed in mice. Overexpression of VHL attenuated liver fibrosis, downregulated fibrogenic genes, and inhibited liver inflammation, apoptosis, and angiogenesis. Overexpression of VHL was more successful at inhibiting fibrosis compared with silencing HIF-1α plus HIF-2α. Normoxia-active HIF-1α or HIF-2α prevented the inhibitory effect of VHL on liver fibrosis, indicating that attenuating fibrosis via VHL is HIF-1α- and HIF-2α-dependent to some extent. In addition, overexpression of VHL inhibited mouse hepatic stellate cells activation and proliferation and promoted apoptosis. Taken together, VHL may be considered a new target to inhibit liver fibrosis.
Published: 2017

73. EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma

Author: Shang Ha Pan, Tong Sen Zheng, Lianxin Liu, Jia Bei Wang, Hongchi Jiang, Ying Jian Liang, Rui Peng Song, Lian Dong Qu, Da Long Yin, Jiaren Liu, and Bo Shi Sun
Subjects: 0301 basic medicine, Apoptosis, Biology, Inhibitor of apoptosis, medicine.disease_cause, Benzylidene Compounds, Article, Metastasis, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, medicine, Humans, Neoplasm Metastasis, Piperidones, Multidisciplinary, Cell growth, NF-kappa B, medicine.disease, XIAP, Cell biology, Neoplasm Proteins, G2 Phase Cell Cycle Checkpoints, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer cell, M Phase Cell Cycle Checkpoints, Signal transduction, Carcinogenesis, Signal Transduction
Abstract: A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment.
Published: 2016
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74. Analysis of 300 consecutive cases of pancreatic adenocarcinoma in a single-center in China

Author: Lianxin Liu, Haiquan Qiao, Jizhou Wang, Hongchi Jiang, Yong Ma, Huayang Pan, Bei Sun, and Han Lin
Subjects: Male, medicine.medical_specialty, China, Time Factors, CA-19-9 Antigen, Perineural invasion, Kaplan-Meier Estimate, 030230 surgery, Adenocarcinoma, Single Center, 03 medical and health sciences, 0302 clinical medicine, Pancreatectomy, Risk Factors, medicine, Humans, Lymph node, Proportional Hazards Models, Chi-Square Distribution, Hepatology, business.industry, Proportional hazards model, Gastroenterology, Middle Aged, medicine.disease, Surgery, Pancreatic Neoplasms, medicine.anatomical_structure, Treatment Outcome, Socioeconomic Factors, Pancreatic fistula, 030220 oncology & carcinogenesis, Multivariate Analysis, Resection margin, Female, Pancreas, business, Hospitals, High-Volume
Abstract: Background Most of the reports on the prognostic indicators of patients with pancreatic adenocarcinoma are from developed countries. The present study focused on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma. Methods A total of 300 patients with pancreatic adenocarcinoma who had undergone curative resection were included. The resection and R0/R1 resection rates for adenocarcinomas from different parts of the pancreas were calculated and clinical characteristics were analyzed. Results In 3427 patients diagnosed with pancreatic adenocarcinomas, only 300 (8.8%) were eligible for radical resection. The total median survival of these patients was 19 months, and their 1-, 3-, and 5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic factors included socioeconomic status, smoking history, symptoms, high blood glucose, and various tumor characteristics, including perineural and vascular invasion, lymph node metastases, and CA19-9 levels before and after operation. Operation-associated prognostic indicators included operation time, blood loss and transfusions, pancreatic fistula, and complications. Independent predictors of mortality included poor socioeconomic status, smoking history, symptoms, CA19-9, perineural invasion and lymph node metastasis, grade of fistula and complications. Patient survival was not correlated with either resection margin or adjuvant chemotherapy in multivariate analysis. Conclusions The survival rates of patients with curative resection for pancreatic adenocarcinoma in China are close to those in developed countries, but curative resection rate is far below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent prognostic factors, which are helpful in patient selection and perioperative care.
Published: 2016

75. Erratum

Author: Sascha Martens, Masashi Narita, Rajkumar Cheluvappa, Kevin A. Roth, Ta Yuan Chang, Kartik Venkatachalam, Chang-Shen Lin, Sharon G. Adler, Flaminia Pavone, Dianwen Ju, Michelle A. Ozbun, Michael R. Duchen, Shu Feng Zhou, Wei-Guo Zhu, Aaron Di Antonio, Defeng Wu, Taixing Cui, Xu Guang Guo, Zhiping Xie, Lorena García Nannig, Eloy Bejarano, Stéphane D. Lemaire, Petro Starokadomskyy, Hyung Ryong Kim, Mario Pinar, Rebecca T. Marquez, Zvenyslava Husak, Anthony R. White, Joanna Poulton, Antonis S. Zervos, Shweta Sharma, Jochen Walter, Nicholas T. Ktistakis, Christopher H.K. Cheng, Sunhee Lee, Yuen Li Chung, Howard O. Fearnhead, Young J. Oh, Ivano Amelio, Guillermo A. Blanco, Jan Simak, Junfang Wu, Yingying Lu, Mary Kate McBrayer, Soo Han Bae, Ichizo Nishino, Hong-Ming Hu, Benjamin R. Underwood, Tomonori Kimura, Zexian Liu, Savithrama P. Dinesh-Kumar, Qian Yang, Andreas Kern, Hsing Jien Kung, Jan B. Parys, Cam Patterson, Celine Perier, Toshiro Okazaki, Daisuke Koya, Avinash Sonawane, Cédric Cleyrat, Robert I. Richards, Kai Y. Soo, Rodrigo Mora-Rodriguez, Gigi N.C. Chiu, Moon Moo Kim, Vladimir N. Uversky, Shengfang Ge, Matthew T. V. Chan, Irene Kyrmizi, Lara Gibellini, Ángela M. Valverde, Erik Norberg, Fan Zhang, Jan C. Koch, Alec C. Kimmelman, Jingfang Ju, Jie Bai, Lei Duan, Paulina Ordonez, Shuwen Liu, Wolfdieter Springer, Eric Deutsch, Elena Ortona, Jose M. Seguí-Simarro, Vinay Choubey, Leonidas Stefanis, Robert G. Hawley, Claudia Bincoletto, Xian-Hui He, Zhifen Yang, Thomas M. Durcan, Martine Biard-Piechaczyk, Kui Lin, Hongming Pan, Konstantinos Kambas, Cristina Muñoz-Pinedo, Marta Magariños, Yoshinori Takahashi, Adrienne M. Gorman, Philippe Gailly, Takahiko Akematsu, Justine D. Mintern, Liang Xu, Tetsuo Shioi, Luis M. Botana, Yule Liu, Yong Yeon Cho, Jinzhi Lei, Eung Kweon Kim, Alakananda Basu, Vikash Kumar Dubey, Candelaria Gomez-Manzano, Avital Eisenberg-Lerner, Chuan-Ming Xie, Wenjie Dai, Pedro Gonzalez-Alegre, Maria Condello, Zheng-Hong Qin, Zhi-Min Yuan, Catherine Andreadi, Anna Rita Migliaccio, Chong Liu, Michaël Boyer-Guittaut, Melanie Denizot, Esperanza Arias, Greet Van den Berghe, Guomei Tang, Timothy P. Devarenne, Xianyong Sheng, Louis R. Lapierre, J. Wade Harper, Zuzana Storchova, Aileen R. Ariosa, Sug Hyung Lee, Qi Zeng, Godefridus J. Peters, Daniela L. Papademetrio, Alexandre Arcaro, Zhiyuan Yao, Pablo Iribarren, Mario Chiariello, Maria Rosaria Torrisi, Parimal Karmakar, Yong Huang, Sebastiano Sciarretta, Nathalie Andrieu-Abadie, László Fésüs, Patricia Boya, Ruediger Rudolf, Leonor Miller-Fleming, Vasilis J. Promponas, Juan Segura-Aguilar, Paula Daza, Shiow Ju Lee, Songshu Meng, Paul K. Herman, Ludwig Eichinger, Ye-Guang Chen, Kay F. Macleod, Thomas Simmet, Cristina Corral-Ramos, Claudio Brancolini, Jun Ren, Ying Jiang, Benoît Derrien, Xiao Fang Yu, Qing Zhong, Zong Wan Mao, Xingcong Ren, Armando A. Genazzani, Marina Pierdominici, Sanbing Shen, Sandra Moreno, Hana Algül, Maurizio Renna, Ricardo Sánchez-Prieto, Ashok K. Saluja, Yasuo Uchiyama, Pope L. Moseley, Victor E. Dosenko, Chun-Feng Liu, Bakhos A. Tannous, Efthimios Sivridis, Baharia Mograbi, Michiko Shintani, Amanda S. Bess, Rodrigo Portes Ureshino, Avnika A. Ruparelia, Paul Hofman, Eric Chevet, Martha M. Monick, Hong Gang Wang, Daping Fan, Jorge Moscat, Giuseppe Matarese, Consiglia Pacelli, Young Seok Cho, Miriam Cnop, Stefan Böckler, Nikolai V. Gorbunov, Christina J. Sigurdson, Hang T.T. Nguyen, Aurélie François, Katarina Kågedal, Sam Gandy, Silvia Campello, Alain Bruhat, Filomena Fiorito, Hua Feng, Man Tian Mi, Gian Maria Fimia, Masaki Tanaka, Guofei Zhou, José L. Crespo, Heinz Jungbluth, Anna Chiara Nascimbeni, Arianne L. Theiss, Svetlana Dokudovskaya, Mar Lorente, Sergio Lavandero, Yu Xia Zhao, Fangming Lin, Yuchen Feng, Gad Galili, Silvia Cetrullo, Paula I. Moreira, Dhyan Chandra, Dimitrios J. Stravopodis, Roberta A. Gottlieb, Gregory A. Taylor, Longping Wen, Faqiang Li, Marco Sardiello, Umesh K. Jinwal, Francesca Belleudi, Lan Tan, Livia Di Renzo, Tamas Korcsmaros, Xinbing Sui, Douglas R. Green, Guillermo Mazzolini, Hervé Le Stunff, Kelly S. Doran, Mary E. Choi, Carlos S. Subauste, Natalia Rodriguez-Muela, Nicholas J. Talbot, Marta Palmieri, Sonia Hernández-Tiedra, Ligia C. Gomes, Irving M. Shapiro, Makoto Ubukata, Mario P. Tschan, Baris Bingol, Benjamin Loos, Terry Kwok, Luca M. Neri, Sreejayan Nair, Michele Wolfe Bianchi, Ralf Erdmann, Alexander Greenhough, Neeraj Vij, Jeong Hun Kim, Satoaki Matoba, Bo Liu, George R. Beck, Michael Moore, Vrajesh V. Parekh, Kyle A. Bauckman, Li-Lin Du, Mikihiro Fujiya, Yan G. Zhao, Renaud Legouis, Jiangwei Zhang, Kailiang Jia, Nadezda Apostolova, Sehamuddin Galadari, Khosrow Adeli, Ming Yong Zhang, Carmela Fusco, Angel Ortega, Anna Pensalfini, Zsuzsanna Szatmári, Marco Tafani, Isabella Ceccherini, Anne Hamacher-Brady, Kuen Jer Tsai, Anita C. Truttmann, Franco Fortunato, Keisuke Miyazawa, Chunhai Fan, Berge A. Minassian, Jian Zhang, Frank A. Anania, Heesun Cheong, Amal O. Amer, Ing Swie Goping, Won-Ki Huh, Anita Solhaug, Joan Cl ria, Laurent Le Cam, Seungmin Hwang, Karen L. Wright, Antonella De Matteis, Troy T. Rohn, Ivana Bjedov, Subbiah Pugazhenthi, Hal E. Broxmeyer, Xue Yuan Bai, Koenraad Norga, Minnie M. Sarwal, Daniel F. Schorderet, Ioannis P. Nezis, Mei Qing Wang, Jun Hee Lee, Yong J. Lee, David A. Tumbarello, Fernando Macian, Joern Dengjel, Dmitry V. Bulavin, Andrew J. Halayko, Ben Berkhout, Aseem Pandey, Santosh Kesari, Karin Przyklenk, Elena V. Tchetina, Matthew L. Albert, Laura Segatori, Joel N. Meyer, Mustapha Rouis, Éva Margittai, Ashish Jain, David Hahn, Thomas Vaccari, Lori R. Covey, Ghanshyam Swarup, Kuo Yang Huang, Gennaro Napolitano, Sam W. Lee, Seong Who Kim, Alberto Anel, Vladimir V. Rogov, Laura A. Carleton, Amine Belaid, Byoung Kuk Jang, Sheng-Han Kuo, Patricia L. Yeyati, Jae U. Jung, Teresa Zoladek, Sabrina Di Bartolomeo, Clémence Richetta, Peixin Yang, Daniela Trisciuoglio, Hye Seung Jung, Katsumi Higaki, Eui-Bae Jeung, Ivan Topisirovic, Isabella Caniggia, Susan E. Logue, Issidora S. Papassideri, Lynda A. Morrison, Caihong Wang, Graeme Sargent, Beth Levine, Mingxiang Ye, David M. Sabatini, Consuelo Amantini, Julio A. Aguirre-Ghiso, Lawrence H. Boise, Patricia Silvia Romano, Sean T. Sweeney, Takayuki Tsukuba, Reinhard Dechant, Benoit Barbeau, Marta Martinez-Vicente, Kuo How Huang, Edésio José Tenório de Melo, Faustino Mollinedo, José M. Fuentes, Joaquín Jordán, Dong-Hyung Cho, Dexian Zheng, Jeroen J.M. Hoozemans, Zhong Chen, Waleska Kerllen Martins, Abraham Acevedo Arozena, Marcos P. Thomé, Gordon C. Shore, Fabienne C. Fiesel, Teng Jiang, Feng Han, Marc Poirot, Anne Sophie Nicot, Eileen White, Olivier Feron, Arthur I. Cederbaum, Wen Bin Qian, Yingjie Sun, Rejko Krüger, Shingo Kajimura, Jianzhen Xu, Shang Der Chen, Maximiliano G. Gutierrez, Zhengping Yu, Jiaren Sun, Utpal Sen, Giovanna Galliciotti, Hilde Nilsen, Benjamin T. Kopp, Benedikt Westermann, Inmaculada Galindo, Eeva-Liisa Eskelinen, Rubem F. S. Menna-Barreto, Guillermo Mariño, Andrea Ballabio, Izabela Poprawa, Yanjin Zhang, Clay F. Semenkovich, Martin E. Fernandez-Zapico, Helin Vakifahmetoglu-Norberg, Hongchi Jiang, Eugenia Morselli, Angelo A. Manfredi, Marianne Boes, Han-Jung Chae, Covadonga Alonso, Min Chen, Safia Costes, David Kessel, Rakesh Kumar, Yang Zhang, Reinhild Prange, Vassiliki E. Mpakou, Laura Santambrogio, Javier E. Irazoqui, Anna Skwarska, Junichi Sadoshima, Rika Umemiya-Shirafuji, Michael I. Koukourakis, Norma Maugeri, Yuqing Wang, Pedro R. Cutillas, Jiqin Lian, Jiri Stulik, Takashi Ueno, Craig Montell, Rena Balzan, Meiyan Jin, Mara C. Duncan, Cathleen R. Carlin, Yasuo Yanagi, Maite G. Fernandez-Barrena, Yuyan Xiong, Martin Graef, Wei Yuan Yang, Renato V. Iozzo, Mark Screen, Patrick Brest, Haichao Wang, Ming Tan, Werner J. Kovacs, Weili Shen, Alessandro Fraldi, Paul Saftig, Alberto Faggioni, Krisna Prak, Christos E. Zois, Timothy E. Weaver, Marc Lecuit, Yu-Ying He, Michele Caraglia, Walter Balduini, M. Isabel G. Roncero, B. Schneider, Monika Cahova, Mathias Faure, Chihiro Sasakawa, Simon Michaeli, Sandy Giuliano, Dario C. Altieri, Eun-Kyeong Jo, Myung-Shik Lee, Carol Imbriano, John H. Brumell, Gustavo H. Goldman, Yan Wang, Junyan Shi, Quan Chen, Jayanta Debnath, Yonggeun Hong, Mohamed Amessou, Richard W. Wong, Robert E. Burke, Mauro De Santi, Trevor G. Shepherd, Anna Maria Joseph, Wouter G. van Doorn, Erkang Fei, Huey Lan Huang, F. Gisou van der Goot, Xinfeng Liu, Alexandru Almasan, Akiko Maeda, Yu Qiu, Yaohua Wu, Annie Sittler, Wen-Xing Ding, Wenhua Zhu, Hung-Jen Liu, Moisés Martínez-Velázquez, Jeffery S. Cox, Seung Yong Yoon, Concepcio Marin, Wilian A. Silveira, Fulvio Chiacchiera, W. Douglas Fairlie, Jian Xin Gao, Shuilong Leng, Nathan R. Brady, Josef M. Penninger, Puran Singh Sijwali, Florian Gruber, Tibor Vellai, Jiunn-Liang Ko, Laura Korhonen, Slimane Ait-Si-Ali, Hirokazu Arimoto, Alberto M. Martelli, Teresa L. M. Thurston, Chuanshan Xu, Kathrin Pallauf, Eduardo Couve, Shweta Saran, Lionel Blanc, Maylin Almonte-Beceril, Yong-Keun Jung, Lena Lavie, Junsoo Park, Camilla Palumbo, Claire H. Mitchell, Sophie Pattingre, Guillermo Velasco, Steve S.-L. Chen, Xiu-Fen Ming, Xin Qi, Vania Gelmetti, Nicolas Dupont, Soraya S. Smaili, Chinnaswamy Jagannath, Uta Dahmen, Daolin Tang, Rodrigo Franco, John H. Kehrl, Xiaonan Dong, Carsten Sachse, Jeff Kuret, Genzou Takemura, Supawadee Sukseree, Joëlle Botti, W. Haung Yu, Aurelia Lugea, Scott J. Bultman, Divaker Choubey, Frank A. Sinicrope, You-Wen He, Jian Wu, Yoshitaka Isaka, Geert Bultynck, Giuseppe Merla, Luigi Maiuri, Sonia Melino, Hannelore Maes, Daniele Lettieri Barbato, Ian G. Ganley, Zhihong Yang, Daniel Hofius, Kimberly McCall, Peiwen Chen, Istvan Lekli, Alicia Rosello, Eric Ghigo, Atsushi Kuno, Iman Tavassoly, Chris Albanese, Agustín Aranda, Salvatore Pepe, Hong Jiang, Henri Batoko, Giovanna Elvira Granato, Vincent Zecchini, Stephen E. Girardin, Maria T. Diaz-Meco, Philippe Marambaud, G. Amadoro, Sangeeta Khare, Christelle Koechlin-Ramonatxo, Emery H. Bresnick, Christian Behl, Mikio Nishimura, Julien Puyal, Wenjie Guo, Hsinyu Lee, Carolyn M. Sue, Derrick Gibbings, Alina Maloyan, Philippe Pierre, Serge N. Manié, Gerry Melino, Elizabeth A. Woodcock, Roberto Ciarcia, Liwen Jiang, Michael C. Kruer, Vladimir Trajkovic, Yunjiao Zhang, Nina Raben, Beata Pajak, Michael J. Ragusa, Riccardo Autelli, Kelly Jean Thomas, Suzana Gispert, Wei Li Zhao, Cheol Hyeon Kim, Pothana Saikumar, Arsenio Fernández-López, Juliano Machado, Valentina Iovane, Cai Ping Tan, Carmine Settembre, Neelam Azad, Yohta Shimada, Shivendra V. Singh, Hai Rao, Hirosato Mashima, Michael T. Stang, Yasuhito Sakuraba, Gemma Fabriàs, Tuck Wah Soong, Didac Carmona-Gutierrez, Ilse Vanhorebeek, F. Javier Oliver, Mondira Kundu, Alfonso Schiavi, Dan Lindholm, José L. Revuelta, Jason S. King, Susana Castro-Obregón, Paul Digard, Hua Zhu, Komal Raina, Yun Dai, Ruben K. Dagda, Nuria Martinez-Lopez, Andrea A. Gust, Lucia Notterpek, Robert Clarke, Manon E. Wildenberg, Mingzhou Chen, Leticia Reyes, Laura Berliocchi, John J. McMahon, Hongzhuan Chen, E.M. Nolte, Stefan W. Ryter, Fulvio Reggiori, Jiefei Geng, Michael A. Mandell, John H. Fingert, Holger Prokisch, Marina Jendrach, Søren R. Paludan, Elizabeth P. Henske, Ricardo Gargini, Wei-Xing Zong, Susmita Kaushik, Michael Overholtzer, Paul W. Sylvester, Daniel E. Voth, Canhua Huang, Andrea Boman, Gérard Lizard, Rut Valdor, Marc Flajolet, Graham S. Taylor, Nicola Di Daniele, Leonardo H. Travassos, Ying Yang, Anumantha G. Kanthasamy, Hasan Mukhtar, Yuhua Zhu, Noor Gammoh, Ignacio Vega-Naredo, Victoria Ryabovol, Sara W. Bird, Gang Min Hur, Qun-Ying Lei, Fan Yi, Laura Caberlotto, Maria F. Galindo, Bilal Piperdi, Leonidas C. Platanias, P. Hande Özdinler, Régis Delage-Mourroux, Julio Madrigal-Matute, Xu Liu, Nagio Takigawa, Aurora Pujol, Marta Margeta, Hee Jeong Kong, Christian Behrends, Michael Thumm, Shirley Luckhart, Emilio Clementi, John W. Steele, Liliana Schaefer, Philip L. Lorenzi, Chao-Yu Miao, She Min Lu, Jane E. Ishmael, Jin Hyoung Kim, V. Izzo, Yanming Wang, Balindiwe J.N. Sishi, Vincent Galy, Andras Perl, Shouqing Luo, Giovanni Vitale, Yongsheng Che, Rodrigo Troncoso, Liu Yang, Thomas J. Begley, Sebastien G. Bouret, Elizete Rizzo, James M. Piret, Junjun Wang, Herman P. Spaink, Thomas S. Jacques, Robin F. B. Turner, Young H. Lee, Eva Szegezdi, Daphne R. Goring, Manish K. Aghi, Rui Kang, Bart Staels, Midori Umekawa, Delia Goletti, Robert J. Bryson-Richardson, Ubaldo E. Martinez-Outschoorn, Luisa Dalla Valle, Giovanni Luca Gravina, Emad S. Alnemri, Maria Kaparakis-Liaskos, Konstantinos Ritis, Shalmoli Bhattacharyya, Alessandra Bolino, Xiaonan Zhao, Yoshihisa Watanabe, Christian Ungermann, Juan L. Iovanna, Katherine Williams, Ken Shirabe, Teresa S. Hawley, Sara Cherry, Ryuichiro Atarashi, Kozo Hamada, Seamus J. Martin, Shigeru Oshima, Mario Pende, Illana Gozes, Michel A. Duchosal, John J. Shacka, Shunhei Yamashina, Kithiganahalli Narayanaswamy Balaji, Richard L. Proia, Besim Ogretmen, Fang Hua, Koichi Araki, Charles Grose, Jia Luo, Helen K. W. Law, Charles Swanton, Liat Drucker, Guo Zhang, Zhizhuang J. Zhao, Anne K. Kenworthy, Javier A. Menendez, Gary Grant, Stig U. Andersen, Frank Lafont, Aparna Lakkaraju, Taijoon Chung, Leticia A.M. Carneiro, Monique Bernard, Gang Chen, Stephen W.G. Tait, Aimee L. Edinger, Jeffrey P. MacKeigan, Paul A. Ney, Mireia Niso-Santano, Valeria Crippa, Andreas S. Reichert, Isabelle Dugail, Jon D. Lane, Farida V. Minibayeva, Gianluca Tettamanti, Scott Pattison, Péter Lõrincz, Kamal Chowdhury, Ulrich E. Schaible, Maria Agnello, Paolo Pinton, Niels Jessen, Lei Guo, Kwang-Huei Lin, David N. Zacks, Ying Jan Wang, Simone Fulda, John J. Lemasters, Andrea Viale, Anna Maria Marconi, Valerie Askanas, Yoshitaka Nagai, François M. Vallette, Joan K. Heath, Srinivasan Dasarathy, Soo-Youl Kim, Günter U. Höglinger, Tamara Kravic-Stevovic, Iraide Alloza, Tiago F. Outeiro, Ana Serrano-Puebla, Elena A. Minina, Terrence M. Donohue, Ming Guo, Alexandra Giatromanolaki, Abdel Halim Harrath, Ken Sato, Anne Elisabeth Theron, Usha P. Andley, Claudio Cardinali, Maija Pesonen, Penny E. Lovat, Chanhee Kang, Sabah N. A. Hussain, Lisa A. Brennan, Jose A. Tapia, Christoph Becker, Huixin Yu, Pei-Yu Wang, Bertrand Joseph, Zhen Yan, Georgia Minakaki, Ricardo Escalante, Ralph A. Nixon, Katsuhiko Asanuma, M. Helena Vasconcelos, David J. Reiner, Shengkan Jin, David Dávila, Theo Rein, Balakrishna L. Lokeshwar, Antonio Miranda-Vizuete, Carl Ward, Vito Turk, Frederick D. Quinn, Katja Köhler, Masaru Harada, Kathleen Boesze-Battaglia, Fraser P. Coxon, Paulo R. Jannig, Miguel A. Peñalva, Manjula Kalia, Marco Corazzari, Chunjuan Song, Xianghua Yan, Lilach Toker, Benjamin Pineda, Vanessa Ginet, Ye Xu, Chun Jung Chen, Roberto Towns, Amy A. Kiger, Rajagopal Ramesh, Maria Rita Rippo, Joseph A. Hill, Boris Zhivotovsky, Peter Speck, Ya Hua, Peter J. Roach, Fabio Penna, Kasper M.A. Rouschop, Jeng-Jer Shieh, Maria Angeles Mena, Mei Zhao, Sonia Rocha, Xin Wen, Sylvain Lefort, Michael Scharl, Ramnik J. Xavier, Alan Cheng, Marion Bouchecareilh, Stella Y. Lee, Maria Xilouri, Qi Chen, Claudia Spies, Pengfei Ge, Natascia Ventura, Luca Galluzzi, Yau Hung Chen, Jing Pu Zhang, Diego Albani, Dingzhong Tang, Nikolai Engedal, Stefania Meschini, Maria Lyngaas Torgersen, Shibu M. Poulose, Jean-Paul Decuypere, Ziheng Xu, Jocelyn Laporte, Thierry Arnould, Albert Haas, Ida J. van der Klei, Agustín Hernández, Dong Wook Shin, Per E. Stromhaug, Valentín Ceña, Ugo Pagnini, Karolina Pakos-Zebrucka, Blagovesta Popova, Lisa M Lindqvist, Sangita C. Sinha, Yuguang Shi, Zvonimir Marelja, Robin Candau, Xin Wang, Evelina Gatti, Olatz Pampliega, Michael P. Lisanti, Elena Tamagno, Mei Lan Tan, Gary Warnes, Zdena Palková, Shigeomi Shimizu, Ingo Schmitz, Tino Kurz, Soledad Matus, Gopal Chakrabarti, Joseph J.Y. Sung, Beáta G. Vértessy, Giuliana Cassinelli, Giovanni Benard, Yin Chen, Emma Colucci-Guyon, Craig Blackstone, Lizhi Cao, Sebastian Schuck, Qingqiu Gong, Theocharis Panaretakis, Jayoung Choi, Sven R. Carlsson, Libuše Váchová, Raymond Chuen-Chung Chang, Yang Liu, Zheng Dong, Qinghua Shi, Hélène Duez, Tiziana Bachetti, Axel H. Schönthal, Sumit Sahni, Bo Wang, Naomichi Matsumoto, Markus Rehm, Liliana Torosantucci, Toren Finkel, Yi Hsin Tseng, Hsiang Cheng Chi, Fang Lin, Tony George Jacob, Ju-Xian Song, Alessandro Fanzani, Marc Tatar, Paola Costelli, Rubén Gómez-Sánchez, Yunfei Wen, Juha J. Hulmi, Francesca V. Mariani, Min Zeng, Chiung Chyi Shen, Carine Michiels, Yan Burelle, Andreas L. Serra, Goran Petrovski, Kwang Woon Kim, Paula Ludovico, Darius Ebrahimi-Fakhari, Yee Joo Tan, Luisa De Martino, Alvaro Glavic, Pierre Lapaquette, Edmund B. Rucker, Andreas Mayer, Shigeko Yamashiro, Scott K. Powers, Robert M. Gogal, Ebru Goncu, Yuichiro J. Suzuki, Anna Maria Giammarioli, Claudio Hetz, Eric H. Baehrecke, Cheryl L. Walker, Cinzia Lanzi, Deepti S. 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Osellame, Maurizio Battino, Małgorzata Gajewska, Maria I. Vaccaro, Darius J.R. Lane, Yuji Ogura, Ian G. Mills, Gil Leibowitz, Joan Villarroya, Yu-Chen Hu, Maria Teresa Batista, Vojo Deretic, Manoj B. Menon, Zhenyi Ma, Dawit A. P. Gonçalves, Iban Seiliez, Enzo Emanuele, Ho Shin Gwak, Arnim Pause, Francesca Palladino, Cristiano Simone, Angelica M. Merlot, Peng Wang, Liang Ge, Kenneth Maiese, Ken Cadwell, Sally S. Atherton, Deepak Shukla, Thomas Neill, Jean-François Beaulieu, Barry Jutten, Cristina P.R. Xavier, James Murray, Tatsuya Saitoh, Roberto Chiarelli, Benedetto Grimaldi, Antonio Giordano, Yanjun Kou, Cathy Tournier, Romana T. Netea-Maier, Rui Li, Jason L. Eriksen, Colin D. Weekes, Esther Barreiro, Denis Mottet, Derek P. Narendra, Karl Swärd, Stephanie E. Wohlgemuth, Gary A. Silverman, Yukitoshi Nagahara, Mark J. Walker, Roland Malli, Diane M. Ward, Ling Hua Meng, John D. MacMicking, Cinzia Fabrizi, Marco Tucci, Tomasz M. Stepkowski, Wannian Yang, Yi Zhen Deng, Daret K. St. Clair, Darren J. Moore, Michael Lee, Katia Aquilano, Norbert Frey, Tibor Kovács, Ru Jeng Teng, Federico Pietrocola, Alfredo Criollo, Nadia Jaber, Walter T. Klimecki, Xiaohong Zhuang, Beata Sikorska, Inmaculada Tasset-Cuevas, Iwona A. Ciechomska, Robert C. Dickson, Haruo Kanno, Hua She, Xiaolei Xu, Maria Laura Avantaggiati, Isei Tanida, Jun Li, Diego Pérez-Rodríguez, Agnieszka Bagniewska-Zadworna, Viktor I. Korolchuk, Thirumala-Devi Kanneganti, Simone Nardin Weis, Thorsten Nürnberger, Guanghui Wang, Luigi Puglielli, Valina L. Dawson, Santosh Chauhan, Carole Kretz-Remy, Po-Yuan Ke, Haijun Bao, Patrícia Sampaio Tavares Veras, Sharad Kumar, Guo-Qiang Chen, Congfeng Xu, Annie M. Joubert, Diego L. Medina, Andrea Hamann, Christian Münz, Hongchuan Jin, Zhen Chen, Cristina López-Vicario, Seung Il Choi, Ivanka Markovic, Ronit Pinkas-Kramarski, Lei Jin, Yonghyun Kim, Michael J. Clague, James D. Johnson, Areti Pantazopoulou, Mohamed Al-Rubeai, Si Chen, Anne Spang, Matteo Bordi, Xiaowei Wang, Stefanie Pöggeler, Terrence M. Donohue-Jr, Aldrin V. Gomes, Jawahar L. Mehta, Yuuki Fujiwara, Mihai G. Netea, Ezra E.W. Cohen, Yunfei Huang, Do Hyung Kim, Guido Lenz, Qian Cai, Chenran Wang, Anna Katharina Simon, Barbara Del Bello, Robert Layfield, Taehoon Chun, Margit Burmeister, Wei Liu, Peter D. Adams, C. K.James Shen, Iva Slaninová, Kathleen W. Scotto, Erinna F. Lee, Mireille Verdier, Fernando J. Peña, Nicola Brunetti-Pierri, Eun-Kyoung Choi, Aleksandra Isakovic, Ju-Hyun Lee, Swapan K. Ray, Ming Chang Hu, Stephen Baghdiguian, Davide Cervia, Brent R. Stockwell, Maurizio Sorice, Andreas Till, Victor M. Darley-Usmar, Horng-Dar Wang, Ken H. Young, Yibin Feng, Néstor L. Uzcátegui, Andreja Erman, Manuela Antonioli, Alicia Torriglia, Michael D. Kim, Kazuyuki Kuchitsu, Fabio Di Domenico, Claudia Giampietri, Fuyong Song, Kevin E. Behrns, Craig Stevens, A. Sue Menko, Joana Liberal, Antonio Di Pietro, Xuejun Jiang, Joseph D. Mancias, Maria Tiziana Corasaniti, Frédéric Gros, Fuxin Wang, Jeremy Thorner, Areechun Sotthibundhu, Gijs R. van den Brink, Andrei S. Chagin, Rossella Menghini, Francesca Bernassola, Chi Li, Sung Gil Chi, Enrico Milan, Jean M. Mulcahy Levy, A. Murat Kaynar, Maria João Sousa, Olga Corti, Simone Cenci, Ting-Fang Wang, Carlos Hernández, Sucheta Telang, Zun-Ji Ke, Atsuo Amano, Lihuan Du, Meera Nanjundan, Lin Zhang, Matthias Gaestel, Bertrand Kaeffer, Andrey S. Tsvetkov, Silvia Carloni, Kazuhisa Hasui, Rosa Puertollano, Vladimir Bumbasirevic, Yongchao Zhao, Carolyn B. Coyne, Allan Caplan, Per Ottar Seglen, Kotb Abdelmohsen, Andreas Buch Møller, Jenny P.-Y. Ting, Raquel Muñoz-Moreno, Markus A. Rüegg, Monica Hagedorn, Hao Zhang, Tomotake Kanki, Edoardo M. Airoldi, Melanie Schwarten, Alfred J. Meijer, Anne Bertolotti, Matteo Bergami, Joëlle Wiels, Claudia Cerella, Eric Asselin, Z. H. An, Spencer B. Gibson, Chunlai Wu, Kai Kaarniranta, Paloma B. Liton, Feng Jun Li, Roberta Nardacci, Ernst J. Wolvetang, Robert C. Bast, Mark S. Cragg, Quentin Liu, Massimo Federici, Hyun Kyu Song, Hua Bai, Xiaotao Li, Nils J. Færgeman, Jason Chesney, Shrawan Kumar Singh, Marcello D'Amelio, Mark Prescott, Georg Auburger, Shazib Pervaiz, Allen Taylor, Diane C. Bassham, Lei Wan, Michinaga Ogawa, Emilia Maellaro, Cynthia Y. He, Chris Jones, Paolo Grumati, Jun-Lin Guan, Hiroyasu Nakano, Eric A. Schon, Roswitha Krick, Yoshihiro Shidoji, Jaime L. Schneider, Dusica Maysinger, Thomas Thum, Paul G. Thomes, Edo Vellenga, Liang Liu, Giuseppe Filomeni, Niramol Savaraj, Rudolf A. Kley, Wei Jung Chen, Bradley L. Baumgarner, Victor H. Villar, Steven Finkbeiner, Kapil Sirohi, Francesco Cecconi, Steven S. Witkin, Steve Jean, André du Toit, Rossella Russo, Irina Petrache, Randy Schekman, Keisuke Hino, Wei Chen, Basil J. Petrof, Daniel E. Frigo, Gyun Min Lee, Paul N. Span, Megumi Inomata, Ivica Arsov, Zhi-Xiang Xu, Saeid Ghavami, Tania C. Felizardo, Konstanze F. Winklhofer, Weidong Han, Jianhua Zhang, Eva Maria Mandelkow, Lydia Alvarez-Erviti, Wanderley de Souza, Pawel P. Liberski, Yang Sun, Cornelia M. Weyand, William D. Hill, Eric J. Brown, Christopher M. Adams, Felix Randow, Jose Luis Rosa, Ivan R. Nabi, Patricia V. Aguilar, Laure Aurelian, Jae-sung Bae, Gábor Juhász, Hing Y. Leung, Karla Kirkegaard, Peter J. O'Dwyer, Daniele Bergamaschi, Thomas Farkas, Tsunenori Saito, Laura Knuppertz, Leyuan Liu, Dongxu Fu, Liesu Meng, Alon Kahana, Viktor Billes, Shohreh Issazadeh-Navikas, Ljubica Harhaji-Trajkovic, Xiangguo Liu, Takahiro Yamada, Ciro Isidoro, Huiping Zhou, William A. Dunn, Takeshi Into, Giampietro Viola, Eumorphia G. Konstantakou, G. William Wong, Peter W. Szlosarek, Jeffrey S. Isenberg, Mikkel H. Vendelbo, Zuzana Papackova, Carlos B. Gonzalez, Hong Zhang, Alkesh Jani, Heidi Kiil Blomhoff, Wen-Li Chen, Simon Sedej, François Bertrand Favier, Marina K. Holz, Mitsunori Fukuda, Gudmundur Vignir Helgason, Fu-Cheng Lin, Inés Díaz-Laviada, Stefaan J. Soenen, Chao Yung Wang, Chee Yin Chai, Pierre-André Bédard, Xiaoxiang Zheng, Peter V. Bozhkov, Han-Ming Shen, Hazel M. Davey, Pedro A. Lazo, Haoxing Xu, Fengtian He, Jean Max Pasquet, Benoit Pasquier, William T. Jackson, Stéphane Duvezin-Caubet, Bertrand Mollereau, Tomohiro Kabuta, Maria Rosa Ciriolo, Peter Hasselblatt, Nihar Ranjan Jana, Jane L. Armstrong, Elisa Giovannetti, Fang Lin Sun, Zhenyu Yao, Shuji Kishi, Pei-Hui Lin, Yingmei Zhang, Limor Avrahami, Kenichi Shibuya, Guillaume Dalmasso, Radovan Vasko, Sharon Prince, Valerie B. O'Donnell, Gordon B. Mills, Hiroshi Aoki, Maryam Mehrpour, Muniswamy Madesh, Guillermo Díaz-Araya, Susan L. Cotman, Marius K. Lemberg, Tilman Grune, Jing Lan Liu, Richard C. Wang, Sandro Goruppi, Hongmin Wang, Robert A. Heinzen, Xiangmei Chen, Nihal Altan-Bonnet, Sung Sik Lee, Hai Jie Wang, Catherine Dargemont, Jie Du, Sofie Claerhout, Edmond Chan, Yi Sun, Xiangbo Wan, Paul Lingor, Shilpa Buch, Gerald M. McInerney, Zhenlong Wu, Guo Chang Zhang, Iain A. McNeish, Suresh Awale, Mark P. Mattson, Srinivasa Subramaniam, Wuhan Xiao, Katsuhiko Mikoshiba, Giancarlo Parenti, Bruno Miguel Neves, Benjamin Dehay, Fatima Teixeira-Clerc, Patricia Huebbe, Calvin K. Yip, Ryan J. Schulze, Pallabi Sarkar, Vladimir I. Titorenko, Johanna Laukkarinen, Martin E. Gleave, Veronika Stoka, Pascal Genschik, Karen Brown, Zhaoliang Su, Walter Malorni, Arlette Darfeuille-Michaud, Vincent C. O. Njar, Jeffrey E. Pessin, Thomas Wileman, Alexander J. Whitworth, Stefano Santaguida, Gustavo A. Nader, Gláucia Maria Machado-Santelli, Marie-Josée Hébert, Skye C. McIver, Scott A. Soleimanpour, Jia-Hong Lu, Fei Liu, Yu Wang, Elisa Motori, Chad A. 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Rosen, Orsolya Kapuy, Simone Di Paola, Thomas J. Evans, Rosa A. González-Polo, Jin H. Son, Kinya Otsu, Tracey R. O’Donovan, Nicolas Pallet, Stefano Toldo, Wafik S. El-Deiry, Allen Kaasik, Jin Tai Yu, Susu M. Zughaier, Gordon W. Laurie, Barbara Guerra, Taeg Kyu Kwon, Priyamvada Dua, Stephen A. Spector, Yingyu Chen, Ayesha N. Shajahan-Haq, Wei Pan, Matthew Campbell, Leo A. B. Joosten, J. Paul Taylor, Julian J. Lum, Matthew J. Justice, Clarissa von Haefen, William K.K. Wu, Gerald Rimbach, Peter Polčic, Jens Schmidt, Saverio Bettuzzi, Xian De Liu, Satoru Kobayashi, Yan Zhang, Ling Tian, Péter Nagy, Mercedes Pozuelo-Rubio, Cheng Jin, Marek Los, Hiroyuki Ishida, Yuji Moriyasu, Maria Teresa Cruz, Jingjing Liu, Anil K. Sood, Roberto Mateo, Antonio Facchiano, J. Mark Cooper, Xiaofeng Yao, Pei Ming Yang, Eli Arama, Marc Diederich, Luc J. W. van der Laan, Robin Ketteler, James Harris, Eui Ju Choi, Grant R. Campbell, Julie D. Atkin, Janos Kriston-Vizi, Sharon L. McKenna, Mila Ljujic, Hirotaka Watada, Harry Ischiropoulos, Shile Huang, Udo Hasler, Ke Li, Josefina Casas, Ken-ichi Isobe, Min Li, Muriel Priault, Vincenzo De Tata, Monique Gannagé, Sakineh Kazemi Noureini, Isao Ishii, Sasanka Ramanadham, Valérie Pierrefite-Carle, Chengyu Liang, Louise Deldicque, Gabriella Cavallini, Afshin Samali, Angelika Amon, Kah-Leong Lim, Lavinia Cantoni, Demetrios G. Vavvas, James E. Haber, Alireza R. Rezaie, Regina Celia Bressan Queiroz de Figueiredo, Cynthia D. Cooper, Masaaki Komatsu, Silvia Alvarez, Gemma Triola, Dong-Yun Ouyang, Razaul Karim, Kostyantyn V. Dmytruk, Bassam Janji, Peter Bütikofer, Indira U. Mysorekar, Hana Popelka, E. Marion Schneider, Carlos Guillén, Gaël Roué, Seung-Hoon Baek, Patrick Auberger, Jun Araya, Sandra M. Cardoso, Gu He, Eduardo C. Filippi-Chiela, Patrick A. Lewis, Wei-Pang Huang, Eric Reits, Cécile Vindis, Trond Lamark, Mehrdad Alirezaei, Takao Setoguchi, Alberto Bartolomé, Chih Peng Chang, Andriy A. Sibirny, Mauro Piacentini, Jing Wang, Kuninori Suzuki, Ludo Van Den Bosch, Kevin N. Dalby, Keiran S.M. Smalley, David K. Ann, Luis F. Moita, Anthony Sanchez, Chin Hsu, Guillermo M. Albaiceta, Vassilis Stratoulias, Attila L. Kovács, Charleen T. Chu, Tewin Tencomnao, Audrey H. Poon, Steve Lancel, José C. Fernández-Checa, Hannah Rabinowich, Heinz D. Osiewacz, Sami Dridi, Kate E. Keller, Thorsten Hoppe, Crispin R. Dass, Jekaterina Erenpreisa, Akira Matsuura, Donna D. Zhang, Ying Zhao, Luisa Coletto, Roy Parker, Georg M. N. Behrens, Alessia Di Nardo, Mian Wu, Alberto Jiménez, Magdalena Rost-Roszkowska, Christopher J. H. Elliott, Pamela J. Yao, Damián Gatica, Rafael Linden, Helena L. A. Vieira, Anand K. Ganesan, Wim Martinet, Frank Madeo, Juliann G. Kiang, Helmut Kramer, Lorrie A. Kirshenbaum, Salvador Ventura, Clemens Steegborn, Zahra Zakeri, Marco Antonio Meraz-Ríos, Masaki Ohmuraya, Michael A. Riehle, Congcong He, Federica Sotgia, Shi-Mei Zhuang, Paul Dent, Jürgen Bosch, Xuejun Wang, Kuan-Chih Chow, Carlos Gorbea, Lisa Gerner, Yuzuru Imai, Jan Gunst, Duncan R. Smith, María Esther Pérez-Pérez, N. Tony Eissa, Michel Roberge, Carmen García-Ruiz, Irfan J. Lodhi, Hongjiao Ouyang, Mustapha Kandouz, Alessio Papini, Jun Sun, Takanobu Otomo, David H. Perlmutter, Jae-Sung Kim, Feng Gao, Åsa B. Gustafsson, Paul M. Salvaterra, Michael Klinkenberg, Or Kakhlon, Abhinav Diwan, Takahiro Shintani, Paola Matarrese, Marc D. Meneghini, Jinsheng Zeng, Xu-jie Zhou, Linda S. Yasui, Rui Sheng, Shiqian Huang, Elizabeth Delorme-Axford, Amélie Bernard, Kevin M. Ryan, Cecília M. P. Rodrigues, Jonathan M. Backer, Harald Stenmark, Hiroaki Adachi, Koichi Sakakura, Fatima Mechta-Grigoriou, Zhi Nong Wang, Ramesh Natarajan, Tian Xia, Marco Folini, Robert A. Screaton, Jane J. Yu, Xian Wang, Gerhard H. Braus, Min Wu, John A. Hanover, Anuj Kumar, Charbel Moussa, Shailendra Anoopkumar-Dukie, Edward A. Fon, Ted Powers, Thomas H. Kawula, Zhe Liu, Jennifer Martinez, Orian S. Shirihai, Mara Cirone, Fen Wang, Machiko Sakoh-Nakatogawa, Yong Xia, Durga Nand Tripathi, James T. Handa, Nadia Zaffaroni, Esther Wong, Carlos López-Otín, Michael E. Cheetham, Harm H. Kampinga, Leopold Eckhart, Paul de Figueiredo, Xueqin Liu, Michael S. Goligorsky, Valentina Sica, Marco Sandri, Wen Qiang Chen, Szabolcs Takáts, Lilach O. Lerman, Akio Kihara, Constantinos Koumenis, Sergio Comincini, Antoinette Lemoine, Marc Bitoun, Zhuo-Wei Hu, Yu Xiong Su, Jeremy C. Mottram, Miguel A. Sanjuan, Richard D. Vierstra, Angelo De Milito, Marjolein van Egmond, Xi-Long Zheng, Kun-Liang Guan, Katrin Juenemann, Ohkmae K. Park, Eisuke Itakura, Bo Yan, Tim Lahm, Yongshun Chen, Kenneth L. van Golen, Federica Rizzi, Guochang Hu, Volker Doetsch, Chengtao Her, Conrad C. Weihl, Jing Hsiung James Ou, Chiou Feng Lin, Dun-Sheng Yang, Bozena Gabryel, Xiao Feng Zhu, Jackie de Belleroche, Charles L. Edelstein, Julie Gavard, Miklós Sass, Maria Chiara Maiuri, Zhendong Zhao, Pu Duann, Julián Pardo, Atsuhiro Ichihara, Lester M. Davids, Swamynathan Ganesan, Shengyun Fang, Hernando Gomez, Yun Chau Long, Mark J. Czaja, Arnaud Echard, Pilar Gonzalez-Cabo, Chuanyong Guo, Katherine L. Cook, Isabel Varela-Nieto, Li Yu, Yi Ran Huang, Binfeng Lu, Athanassios D. Velentzas, Koji Yamanaka, Giuseppe Russo, Ester M. Hammond, Kelsey B. Law, Sheng Li, Samisubbu R. Naidu, Michael E. Boulton, Anna-Mart Engelbrecht, Ba-Bie Teng, Zixu Mao, Vania M.M. Braga, Núria S. Coll, Eliana M. Coccia, Akihisa Abe, V. Ashutosh Rao, Nava Segev, Regina Menezes, Zufeng Ding, Hyman M. Schipper, Álvaro F. Fernández, Peter K. Kim, Lucia Micale, Biplab Dasgupta, Nazzy Pakpour, Janna L. Morrison, Yue Qin Chen, Rolf J. Craven, Zvulun Elazar, Anders Aune Tveita, Lian Li, Hsueh Fen Juan, Ulrich Koenig, Qiang Shi, Harald W. Platta, Michele S. Swanson, Olga V. Voitsekhovskaja, Bruce H. Reed, Malene Hansen, Paola Lenzi, Sandra Cottet, Yacine Graba, Christian Frezza, Bernd Schröder, Helene Knævelsrud, Li Chung Hsu, Hyunjung Jade Lim, Michael T. Greenwood, Parco M. Siu, Kyu Lim, Dolores Pérez-Sala, Patrice Codogno, Yi Yang, Frank Lezoualc'h, Ida Perrotta, Elaine A. Dunlop, Jörg H W Distler, Ken Ichi Yoshida, Dominic P. Del Re, Luigina Romani, Hye Young Kim, Eric Jonasch, Rajesh Agarwal, Wei Song, Ai Yamamoto, Zully Pedrozo, Steffan T. Nawrocki, María Salazar-Roa, Jorrit M. Enserink, Dong Wang, Flaviano Giorgini, Takayuki Ohshima, Boris Turk, Anastasia S. Mihailidou, Rosa Salvioli, Anne Simonsen, Caroline Biagosch, Glauber Costa Brito, Junko Oshima, Gail V.W. Johnson, Emmanuel Taillebourg, Sovan Sarkar, Shane Deegan, Eldad Zacksenhaus, Laura Avagliano, Byung-Hoon Lee, Weiliang Xia, Paolo Paganetti, Timothy J. Lyons, Christine M. Stellrecht, Jane E.B. Reusch, Raquel T. Lima, Feng Xu, James M. Phang, Hongwei Xu, Claudio Luparello, Mohammad Ishaq, Maureen E. Murphy, Isabelle Coppens, Luc Dupuis, Elio Ziparo, Patrick J. Bednarski, Svetlana Saveljeva, Ashok Kumar, Hongxin Zhu, Tobias B. Huber, Günther Weindl, Claudine Kraft, Dhiraj Kumar, Sara Marinelli, Karin von Schwarzenberg, Lijun Jia, Tiziana Crepaldi, Ke Liu, Eleonora García Véscovi, Qing Lu, Cláudia N. Santos, Bertrand H. Rihn, Jun Yu, Fen-Biao Gao, Flavio Flamigni, Jason E. Gestwicki, Dong-Hun Bae, Gustavo C. MacIntosh, David A. Leib, Giorgio Santoni, Chin Yuan Hsu, Abdelhaq Rami, Joseph Satriano, Matthew J. LaVoie, Paloma Martín-Sanz, Daniela De Zio, Sharon M. Gorski, Yu Tian Wang, Shuyan Lu, Clara L. Oeste, Andrew R. Tee, Koji Itahana, Xuesong Yang, Shuiping Tu, Malathi Krishnamurthy, Anne M. Strohecker, Gui Xian Xia, Helena Orozco, Sujit K. Bhutia, Hongbo Hu, Rupert Beale, Ying-Ray Lee, Kai Mao, Pierre-Emmanuel Rautou, Jean Francois Groulx, James A. Mastrianni, Victoria El-Khoury, Koji Okamoto, Mark J. Taylor, Arianna L. Kim, José M. Izquierdo, Dalibor Mijaljica, Björn Stork, Thomas Schwarz, Savita Bhalla, Menno van Lookeren Campagne, Long Zhang, Elizabeth S. Yeh, Li Zhang, Tae Cheon Kang, Frederic Luciano, Shusaku Shibutani, Luciana Dini, Valentina Cianfanelli, Sara Calatayud, Yong-Sun Kim, Maurizio Molinari, Graham H. Coombs, Takeshi Noda, Angelo Poletti, Silvia Palumbo, Dhan V. Kalvakolanu, Valérie Vouret-Craviari, Volodymyr Y. Nazarko, Salvatore Florio, Noboru Mizushima, Arthur Kaser, Shigeki Miyamoto, Patric J. Jansson, Thomas I-Sheng Hwang, Daniel J. Jackson, Adrian L. Harris, Srikanta Dash, Yeong Min Yoo, David Colecchia, Ute C. Meier, Yi Ma, Tadashi Suzuki, Anand Krishnan V. Iyer, Flavia Radogna, Paul S. Brookes, Deepak Kumar, Gabriella D'Orazi, Barry Yedvobnick, David R. Soto-Pantoja, Christian Waeber, Craig McCormick, Dong Hu, Sarron Randall-Demllo, Gustavo J.S. Pereira, Emil Rudolf, Scott L. Friedman, Paolo Bonaldo, Oliana Carnevali, Guido R.Y. De Meyer, Alice Carrier, Yipeng Wang, Serena Montagnaro, Nadeem O. Kaakoush, José de la Fuente, Devrim Gozuacik, Edward D. Plowey, Alastair M. Buchan, John C. Chatham, Daniel J. Klionsky, Cecilia Gotor, Isabelle Hamer, Katarzyna Mnich, Paola Rusmini, Chengshu Wang, Per Nilsson, Lorena Esteban-Martínez, Raúl V. Durán, Dieter Willbold, Hye Won Chung, Janet D. Sparks, John M. Lucocq, Blake B. Rasmussen, Takeshi Matsuzawa, Hagai Abeliovich, Wiep Scheper, Sung Joon Lee, Jennifer S. Carew, Serena Carra, Michael J. Morgan, Nikolai Slavov, Guy Berchem, Tiziana Cocco, Simone Engelender, Jianbo Yue, Yujie Chen, Mario Fabri, Maria F. Czyzyk-Krzeska, Hua Niu, Roger J. Davis, Peter J. Adhihetty, Kishore B.S. Pasumarthi, Jongsook Kim Kemper, Sharon A. Tooze, Antonio Zorzano, Jin Cheon Kim, Jian Xu, Andreas Meryk, Kristina Vuori, Jongdae Lee, Patrizia Agostinis, Diego Ruano, Wim Vandenberghe, Julia I-Ju Leu, Céline Gongora, Bernadette Carroll, Vinoth Kumar Megraj Khandelwal, Bo Lu, Marja Jäättelä, Lorenzo Galluzzi, Ioannis P. Trougakos, Tatsuya Maeda, Marie-Agnès Bringer, Mario Chiong, Hans-Uwe Simon, Lance A. Liotta, Ruth S. Slack, Ina Oehme, Umamaheswar Duvvuri, Shaun Martin, Augustine M.K. Choi, Michel Vidal, Ying Wang, Isis do Carmo Kettelhut, Mojgan Djavaheri-Mergny, Jörn Coers, Massimo Donadelli, Jesus Aldudo, Miyuki Sato, Jianxun Liu, Jörg Höhfeld, Luc Van Kaer, Andrei I. Ivanov, Dohun Pyeon, José M. Bravo-San-Pedro, Jianxin Peng, Xiaoyan Jiang, Dimitri Krainc, Yangqing Xu, Arnaud François, P. Robin Hiesinger, Sagar Lonial, William C. Cho, Caty Casas, Betty Yuen Kwan Law, Hongbing Zhang, Tor Erik Rusten, Erwin Knecht, Honglin Luo, Shi Xiao, Hiromi Sesaki, Enza Maria Valente, Verónica Pérez de la Cruz, Marta M. Lipinski, David A. Hood, Shi-Yong Sun, Luiz Carlos Carvalho Navegantes, Joynal Abedin, Shino Goto-Yamada, Gustavo Maegawa, Takehiko Matsushita, Vitor A. Lira, Clara I. Rodríguez, Ekihiro Seki, Qiang Li, Karin Öllinger, Ted M. Dawson, Ssang-Goo Cho, Wan-Wan Lin, Pramod Kumar Garg, Jeffrey Robbins, Peter R. Williamson, Michael Sacher, Carlo Follo, Bulent Ozpolat, Xiao Jia Wang, Na Man, Hua Cheng, Bing Yan, Tsung-Hsien Chuang, Paul B. Fisher, Rajat Singh, Edward A. Ratovitski, Katsuhiko Kitamoto, Jung Jin Hwang, Shinji Hadano, Che Hsin Lee, Shuo Wang, Einar M. Sigurdsson, Camille Martinand-Mari, Agnieszka Sirko, Katherine R. Parzych, Etienne Morel, Yasushi Kitaoka, Hassan Chaachouay, Patricia Chakur Brum, Dexin Kong, Jerome Tamburini, Kuppan Gokulan, Stefan Olsson, Bilon Khambu, Lea M.D. Delbridge, Daniel P. Orban, David A. Gewirtz, Zhonglin Xie, Joe Quadrilatero, Kunikazu Tanji, Simin Mohseni, Gábor Bánhegyi, Jin Ming Yang, Jinxian Xu, Carmen Veríssima Ferreira-Halder, Addanki P. Kumar, Deok Ryong Kim, Jianjie Ma, Sang Won Suh, Guido Kroemer, Klára Megyeri, Michael N. Sack, Heinrich Taegtmeyer, Gilles Pagès, Gabriella Marfe, Gregg L. Semenza, Karine G. Le Roch, Marisa Brini, Marina Bouché, Oliver Kepp, Vinay V. Eapen, J. David Beckham, Stephan T. Stern, Xudong Zhang, Marcello Pinti, Xiangnan Zhang, Jae Keun Lee, Ana Coto-Montes, Assaf Rudich, Laura D. Attardi, Debabrata Ghosh, Philip Rosenstiel, Sébastien Besteiro, Maria Rosa Sarrias, R. Andres Floto, Xiao Ming Yin, Nicholas W. Lukacs, Hermann Pavenstädt, Matias Simons, Hitoshi Nakatogawa, Sandro Alves, Krisztina Takács-Vellai, Masato Koike, Debasish Sinha, Shoji Notomi, Faraj Terro, Maria Carmela Roccheri, Santiago Ambrosio, K. Ulrich Bayer, Yumin Li, Terje Johansen, Christian Kuhn, Yee Shin Lin, David C. Rubinsztein, Ziwei Qu, Ronit Shiri-Sverdlov, Emmanuel T. Akporiaye, Galila Agam, Hui Ling Chiang, Seung-Jae Lee, Yu Xue, Francesca Giampieri, Markus Damme, Tassula Proikas-Cezanne, Tianwei Lin, Marc Kantorow, Guang-Chao Chen, Qiangrong Liang, Claudia Manzoni, Joan S. Steffan, Emilio Boada-Romero, Damien Freyssenet, Sepp D. Kohlwein, Maria D. Barrachina, Yulin Liao, Jiankang Chen, Erika Isono, Hugo Seca, Mei Wang, Taras Y. Nazarko, Yannick Bailly, Nadya V. Koshkina, Tapas K. Maiti, Bärbel Rohrer, Karin Nowikovsky, James H. Hurley, Gerald W. Dorn, Nils C. Gassen, Kazuhiro Nagata, Eiki Kominami, A. Ivana Scovassi, Ana Maria Cuervo, Adi Kimchi, Minghua Yang, Sylviane Muller, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Defense in Plant-Pathogen Interactions [Nagoya, Japan], Nagoya University-Graduate School of Bioagricultural Sciences [Nagoya, Japan], Facultad de Quimica [Santiago], Pontificia Universidad Católica de Chile (UC), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain, Harvard University Statistics Department, Harvard University [Cambridge], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry and Molecular Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Centro de Estudios Farmacológicos y Botánicos [Buenos Aires] (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Thérapie génique, Génomique et Epigénomique (U 1169), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Department of Experimental Medicine and Public Health, University of Camerino, MRC Toxicology Unit, University of Leicester, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Departamento de Bioquímica y Biología Molecular y Celular, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Department of Molecular Genetics [Rehovot, Israël], Weizmann Institute of Science, Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre-Dame de la Paix, Département Advanced Research And Techniques For Multidimensional Imaging Systems (ARTEMIS), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Giannina Gaslini Institute, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Department of Cancer Biology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Inner Mongolia Agricultural University (IMAU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Indian Institute of Science [Bangalore] (IISc Bangalore), Politecnico di Milano [Milan] (POLIMI), Département des Sciences Biologiques [Montréal], Université du Québec à Montréal (UQAM), Laboratory of Molecular Biology, Scientific Institute E. Medea, Université Catholique de Louvain (UCL), Univ Ancona, Politecn Marche, University of Toronto, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Department of Clinical and Molecular Medicine, Università degli Studi di Roma 'La Sapienza' [Rome]-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hémato-Cancérologie Expérimentale, CRP-Santé, Dpt of Neuroscience and Brain Technologies [Genova], NeuroEngineering & bio-arTificial Synergic SystemS Laboratory [Genova] (NetS3 Lab), Istituto Italiano di Tecnologia (IIT)-Istituto Italiano di Tecnologia (IIT), Center for Infection and Immunity Amsterdam (CINIMA), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology and Immunology, Stanford University School of Medicine [CA, USA], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Dermatology, Brigham and Women's Hospital [Boston], San Raffaele Scientific Institute, Milan, Italy, Laboratory of Molecular Neuroembryology, University of Rome 'Tor Vergeta'-Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma]-Dulbecco Telethon Institute, Department of Pharmacology, Universidade de Santiago de Compostela, Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Complexo Hospitalario Universitario A Coruña, Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Florida [Gainesville], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infection bactérienne, inflammation, et carcinogenèse digestive, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Padova, University of British Columbia (UBC), University of Edinburgh, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Australian Regenerative Medicine Institute, Monash University, Clayton, 3800, VIC, Australia, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], Department of Biological Sciences [Stanford], Stanford University [Stanford], Université de Montréal (UdeM), Department of Human Genetics, Department of Psychiatry, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Centre for Computational and Systems Biology (COSBI), Department of Computer Science [Tsukuba], Graduate School of Systems and Information Engineering [Tsukuba], University of Tsukuba-University of Tsukuba, Institut de biochimie et génétique cellulaires (IBGC), University of Western Ontario (UWO), Genetics, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Department of Biochemistry and Biophysics, University of Naples Federico II, Lund University [Lund], Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), Karl-Franzens-Universität Graz, Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Cell Biology, Physiology and Immunology, Research Unit on BioActive Molecules, Departamento de Química Orgánica Biológica, Instituto de Investigaciones Quimicas y Ambientales de Barcelona, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), The Buck Institute for Age Research, University of Pisa - Università di Pisa, Laboratorio di Genetica Molecolare, Istituto Gaslini, Universidad de Castilla-La Mancha (UCLM), Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, University of Crete [Heraklion] (UOC), Division of Molecular and Cellular Pathology [Birmingham], Department of Medical Research, Taichung Veterans General Hospital, Modélisation et Simulation Numérique en Mécanique et Génie des Procédés (MSNMGP), Université de la Méditerranée - Aix-Marseille 2-Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), University of Queensland [Brisbane], Dept of Mathematics, Purdue University, Purdue University [West Lafayette], Virologie et Pathologie Humaine (VirPath), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Zhejiang University, Équipe Micro et nanosystèmes HyperFréquences Fluidiques (LAAS-MH2F), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), King Abdullah University of Science and Technology (KAUST), Southern University of Science and Technology of China (SUSTech), OASE, National University of Tainan, Taiwan (OASE), National Taiwan University [Taiwan] (NTU), Weifang Bureau of Land Resources [Weifang], Department of cardiology [Guy's and St. Thomas ' hospitals] [London], Guy's and St Thomas' Hospital [London]-Guy's Hospital [London], University of Pennsylvania [Philadelphia], CRLCC Eugène Marquis (CRLCC), Emory University School of Medicine, Emory University [Atlanta, GA], Korea University, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology [Tartu, Estonie], Institute of Biomedicine and Translational Medicine [Tartu, Estonie], University of Tartu-University of Tartu, Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Experimental Medicine, Oxford University, University of Oxford [Oxford], Division of regenerative Medicine, San Raffaele Scientific Institute, The University of New Mexico [Albuquerque], Université Libre de Bruxelles [Bruxelles] (ULB), Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Institut Gustave Roussy (IGR), Universidad Autonoma de Madrid (UAM), Cell Signalling & Proteomics Group [Londres, Royayme-Uni], Barts Cancer Institute [Londres, Royayme-Uni], Queen Mary University of London (QMUL)-Queen Mary University of London (QMUL), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Department of Biomedical Engineering, The University of Texas at Austin, University of Texas at Austin, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Fondazione Santa Lucia (IRCCS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Biology, Johns Hopkins University (JHU), Neurogenetics Group, Instituto de Investigación en Recursos Cinegéticos (IREC), Laboratório de Ultraestrutura Celular Hertha Meyer (IBCCF), Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Molecular and Cellular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National University of Ireland [Galway] (NUI Galway), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Freiburg Institute for Advanced Studies-LifeNet, Albert-Ludwigs-Universität Freiburg, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Brunel University London [Uxbridge], Unité Propre de Recherche 2357, Institution de Biologie Moléculaire des Plantes, Radiothérapie moléculaire (UMR 1030), Department of Chemistry, University of Kentucky, Universidad de Córdoba [Cordoba], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Facultad de Ciencias Químicas y Farmacéuticas, Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology, Goethe-University Frankfurt am Main, Department of Biological and Environmental Sciences and Technologies (DiSTeBA), Università del Salento, Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Institut National Polytechnique de Lorraine (INPL), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Trafic membranaire et Division cellulaire, Landesbetrieb Hessisches Landeslabor, Hematology-Oncology Division, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Pavia, Instituto de Investigaciones Biotecnológicas [San Martín] (IIB-INTECH), Universidad Nacional de San Martin (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Helsinki, School of Physics and Astronomy [Exeter], University of Exeter, Department of Biomedicinal Chemistry (CSIC), Institut de Química Avançada de Catalunya, Laboratory of Vascular Pathology (IDI-IRCCS), Istituto Dermopatico dell'Immacolata, Peking University [Beijing], MRC Centre for Developmental Neurobiology, University of Brescia, Immunobiologie fondamentale et clinique, Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), University of Rome 'Tor Vergeta', Universidad de Oviedo [Oviedo], Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Dulbecco Telethon Institute/Department of Biology, Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Rockefeller University [New York], The Babraham Institute, Kansas State University, McGill University, Service d'Anatomie et Cytologie Pathologique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), ATOS Origin, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences-Tohoku University [Sendai], Goethe-University, Goethe-Universität Frankfurt am Main, Institute of physiological chemistry, Hannover Medical School [Hannover] (MHH), Department of Physiology, Department of Plant and Environmental Sciences, Apoptose, cancer et immunité (U848), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Institute of Experimental Immunology - IEI [Zürich, Switzerland], Université de Zurich [Switzerland], Digital Enterprise Research Institute (DERI-NUIG), Spanish National Research Council (CSIC), Cell Death Research and Therapy Unit [Leuven, Belgium] ( Department of Cellular and Molecular Medicine), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCINA - Département ONCO - Equipe 15), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Medicine [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Histology, Forensic Medicine and Orthopedic, N.A., Division of Pharmacology and Chemotherapy, Department of Internal Medicine, Pathogénie Microbienne Moléculaire, University of Chile [Santiago], Université de Montpellier (UM), Faculdade de Ciências Farmacêuticas de Ribeirão Preto [São Paulo], Universidade de São Paulo (USP), Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Catalan Institute of Oncology, Department of Cell Biology, National Institute for Basic Biology [Okazaki], Instituto de Bioquímica Vegetal y Fotosíntesis (IBVF), Universidad de Sevilla-Centro de Investigaciones Científicas Isla de la Cartuja, The Adams Super Center for Brain Studies, Tel Aviv University [Tel Aviv], Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and biochemistry, Virginia Commonwealth University (VCU), Department of Immunology, St Jude Children's Research Hospital, Department of Biology and Biotechnologies 'Charles Darwin', Lettres, Idées, Savoir (LIS), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute of Biological Chemistry and Nutrition, University of Hohenheim, China Seismological Bureau, Massachusetts Institute of Technology (MIT), Rosenstiel Basic Medical Sciences Research Center [Waltham], Brandeis University, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Meakins-Christie Laboratories, Sanford Burnham Medical Research Institute, La Jolla, National Institute of Advanced Industrial Science and Technology (AIST), ORIENT ET MÉDITERRANÉE : Textes, Archéologie, Histoire (OM), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Biochemistry and Molecular Biology I, Department of Immunology and Infectious Diseases, Harvard School of Public Health, aDepartment of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences (SLU), Philipps University of Marburg, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Rural Health Academic Centre, University of Melbourne-Rural Clinical School, Department of Pathology, University of Veterinary and Animal Sciences, Dipartimento di Scienze della Vita [Modena, Italy], Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Anatomy & Cell Biology [Philadelphia, Pennsylvania, USA], Thomas Jefferson University, Department of Molecular Neuroscience, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Centro de Investigación en Bioquímica Clínica e Inmunología (CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina, Neuroinflammation Unit, Biotech Research and Innovation Centre-University of Copenhagen = Københavns Universitet (KU), Mathematics and Computing in Automatic Control and Optimization for the User (MIAOU), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Danish Cancer Society, Institute of Cancer Biology, UCL-Institute of Child Health (ICH), Institute of Child Health-Great Ormond Street Hospital for Children [London] (GOSH), Division of Renal Diseases and Hypertension, University of Colorado [Boulder], Institut de biologie et chimie des protéines [Lyon] (IBCP), Joslin Diabetes Center, Universität Ulm - Ulm University [Ulm, Allemagne], Qingdao Institute of Marine Geology, China Geological Survey, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Institute of Software, Chinese Academy of Sciences [Beijing] (CAS), Metabolic Engineering Group, Departamento de Microbiologia y Genetica, Edificio Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, University of Minnesota [Twin Cities], University of Minnesota System, Department of Cellular and Molecular Physiology, Yale University School of Medicine, The Arctic University of Norway, Department of Biological Sciences, The Open University [Milton Keynes] (OU), Summit Analytical, CALRG, Institute of Educational Technology, Institute for Neurologic Disabilities Research, Faculty of Health Sciences-University of Pretoria [South Africa], Department of Paediatric Neurology, Guy's and St Thomas' Hospital [London]-Evelina Children's Hospital, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Dana-Farber Cancer Institute and the Department of Cell Biology, Harward Medical School, Translational Health Science and Technology Institute [Faridabad] (THSTI), Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, School of Reliability and Systems Engineering [Beijing], Beihang University, Oxford Centre for Integrative Systems Biology, Center for Membrane and Cell Physiology [Charlottesville, VA, USA] (School of Medicine), University of Virginia [Charlottesville], Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Karlsruher Institut für Technologie (KIT), Faculty of Pharmaceutical Sciences, Hokkaido University, École normale supérieure - Paris (ENS Paris), School of Electrical Engineering [Seoul] (Korea University), Department of Mathematics and Statistics [Guelph], University of Guelph, Department of Molecular Genetics, Department of Genetics [Stanford, CA, États-Unis], Institute of Immunology, University Hospital Schleswig-Holstein, Arizona Respiratory Center, Okazaki Institute for Integrative Bioscience, ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Newcastle University [Newcastle], JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Department of Neuroscience, University of Texas Southwestern Medical Center [Dallas], Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Laboratory of Functional Neurogenomics [Tuebingen, Germany], University of Tuebingen-Center of Neurology and Hertie-Institute for Clinical Brain Research [Tuebingen, Germany], Indian Institute of Technology Bombay (IIT Bombay), European Organization for Nuclear Research (CERN), Harvard Medical School [Boston] (HMS), Indian School of Mines, Department of Computer Science [UIUC] (UIUC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, Centre for Cancer Biology, Hanson Institute, Adelaide, University of California [San Diego] (UC San Diego), University of California, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry, University of Bristol, Organisation Nucléaire et Oncogenèse, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FONDAP Center CEMC Estudios Moleculares de la Célula, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Chungnam National Univesity School of Medicine, Taejon, Korea, Chungnam National Univesity School of Medicine, Micro & Nanobiotechnologies, Institut des Sciences Analytiques (ISA), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Center for Applied Mathematics, Tsinghua University [Beijing], University of Connecticut School of Medicine, University of Connecticut (UCONN), Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes (LBMCE), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et Physiopathologie de la Differenciation, Division of Nephrology and Hypertension, Mayo Clinic, Beatson Institute for Cancer Research, Beatson institute for cancer research, Howard Hughes Medical Institute, Howard Hugues Medical Institute, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Computing Technology [Beijing] (ICT), Chinese Academy of Sciences [Changchun Branch] (CAS), School of Electronics and Computer Science (ECS), University of Southampton, Third Hospital, Department of Anesthesiology, Cognitive Interaction Technology [Bielefeld] (CITEC), Universität Bielefeld = Bielefeld University, Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Faculty of Pharmacy- University of Coimbra, National Neuroscience Institute, Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Coll Life Sci, Beijing Normal University, Delft University of Technology (TU Delft), Christian-Albrechts-Universität zu Kiel (CAU), Department of Molecular Pathology and Microbiology, Center for Applied Proteomics and Molecular Medicine-George Mason University [Fairfax], Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Department of Chemistry, University of Pittsburgh, University of Pittsburg, Tianjin University of Science and Technology (TUST), Hunan University of Science and Technology [Xiangtan], Laboratoire de Génie Civil et Génie Mécanique (LGCGM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), China Agricultural University (CAU), Acad Disaster Reduct and Emergency Management, Minist Civil Affairs, Minist Educ, Beijing, Peoples R China, affiliation inconnue, Département Technologie des Polymères et Composites & Ingénierie Mécanique (TPCIM), École des Mines de Douai (Mines Douai EMD), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Ministère de l'Economie, des Finances et de l'Industrie, MOE Key Laboratory of Bioinformatics, Centre for Plant Biology, School of Life Sciences, Laboratoire d'Informatique Gaspard-Monge (ligm), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Center for International Blood and Marrow Transplant Research (CIBMTR), Emory University [Atlanta, GA]-Medical College of Wisconsin, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Illman Cancer Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Ingénierie des Matériaux Polymères (IMP), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Department of Medical Microbiology and Immunology, University of California [Davis] (UC Davis), School of Health Sciences, University of Minho [Braga], Équipe Calcul Distribué et Asynchronisme (LAAS-CDA), University of California [Riverside] (UCR), Ohio State University [Columbus] (OSU), Laboratory of Systems Biology, Van Andel Institute [Grand Rapids], Division of Genetics and Cell Biology, National Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Oregon Health and Science University [Portland] (OHSU), Dendrite Differenciation Group [DZNE - Bonn], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Equipe 12, Génétique moléculaire, signalisation et cancer (GMSC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Medical Center [Utrecht], Institut d'Investigacions Biomèdiques August Pi I Sunyer [Barcelona, Spain] (Hospital Clinic ), Department of Genetics, Trinity College Dublin, Fisiopatologia de los procesos inflamatorios, Vall d'Hebron Research Institute, Institució Catalana de Recerca i Estudis Avançats (ICREA), Department of Human Genetics, Nagasaki University, Transduction du signal et oncogénèse, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie, Center for Experimental and Molecular Medicine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of medical Biochemistry, University of Amsterdam [Amsterdam] (UvA), IDI-IRCCS Biochemistry Laboratory, Università degli Studi di Roma Tor Vergata [Roma], Program Against Cancer Therapeutic Resistance/Metabolism & Cancer Group [Catalonia, Spain] (ProCURE), Catalan Institute of Oncology-Girona (ICO-Girona), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa (NOVA), Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, CNR, Consiglio Nazionale delle Ricerche (CNR), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, The Hospital for sick children [Toronto] (SickKids), Universidad de Sevilla, Immunité muqueuse et vaccination, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), DIMS, University of Trento [Trento], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Department of Cellular and Molecular Medicine [Madrid, Spain], Laboratory of Cell Death and Cancer Therapy [Madrid, Spain], Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC) -Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3HD, UK, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dpt. of Cancer & Cell Biology, Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Max planck Institute for Biology of Ageing [Cologne], Euromov (EuroMov), Wellcome Trust Centre for Molecular Parasitology [Glasgow, UK], University of Glasgow- Institute of Infection, Immunity and Inflammation [Glasgow, UK], Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), UMR 1599, Centre National de la Recherche Scientifique (CNRS), EA 4100, Histoire culturelle et sociale de l'art (HiCSA), Université Panthéon-Sorbonne (UP1)-Université Panthéon-Sorbonne (UP1), Centre for Astrophysics and Supercomputing (Centre for Astrophysics and Supercomputing), Swinburne University of Technology [Melbourne], Department of Cellular and Physiological Sciences [Vancouver, BC, Canada] (Life Sciences Institute), University of British Columbia (UBC)-Life Sciences Institute [Vancouver, BC, Canada], School of Pharmacy, Department of Experimental Medicine, Dept. Neurosciences, Department of Internal Medicine, Radboud University Medical Center [Nijmegen], Institute of Medical Genetics and Applied Genomics, Radiation Physics, School of Life Science, Department of Basic Biology, The Graduate University for Advanced Studies, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Doshisha University, National Cancer Research Center [Tokyo, Japan], University of Washington [Seattle], Department of Experimental Neurodegeneration [Göttingen, Germany], University Medical Center Göttingen (UMG), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), BioCeV-Institute of Microbiology, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto di chimica biologica, Università degli Studi di Verona, Département Image et Traitement Information (ITI), Institut Mines-Télécom [Paris] (IMT)-Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne, Department of Cell Biology and Biophysics, Università degli Studi di Firenze [Firenze], Cell Immunity in Cancer, Inflammation and infection Group [Zaragoza, Spain] (Biomedical Research Center), Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain]-University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pediatrics, Università degli studi di Napoli Federico II, Transfert de Genes a Visee Therapeutique Dans les Cellules Souches, Developpement Normal et Pathologique du Système Immunitaire, Signalisation et physiopathologie des cellules épithéliales, Facultad de Medicina, Universidad de Santiago de Chile [Santiago] (USACH), Departamento de Farmacobiología, Cinvestav-Sede Sur, Centre de recherche Croissance et signalisation (UMR_S 845), College of Life Sciences, Central China Normal University, Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Laboratory of Cardiac Surgical Research, Monash University [Clayton], Universidade do Minho, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neurodegenerative Diseases Research Group (CIBERNED), Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Barcelona, Department of medicine, Syracuse, NY, USA, State University of New York (SUNY), National University of Singapore (NUS)-Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, McGill University Health Center [Montreal] (MUHC), National Institute for Infectious Diseases, Transporteurs en Imagerie et Radiothérapie en Oncologie (TIRO - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biomedical Sciences, Department of Genetics of Eukaryotic Microorganisms, Georg-August-University [Göttingen]-Institute of Microbiology and Genetics, Sterol metabolism and therapeutic innovations in oncology, Institut Claudius Regaud, CRLCC Institut Claudius Regaud-CRLCC Institut Claudius Regaud-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Molecular, Cellular and Developmental Biology, Señalización Celular 4, Institute of integrative biology (Liverpool), University of Liverpool, Department of Human Biology, University of Cape Town, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Department of Molecular Biology, Eberhard Karls Universität Tübingen, Technical University of Munich (TUM), Biophysics and Bioinformatics Laboratory, Department of Cell Biology and Morphology, Université de Lausanne (UNIL), Shenyang Institute of Automation, the Chinese Academy of Sciences (SIA), Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, Xi'an Jiaotong University (Xjtu), Dipartimento di Biologia, Mechanics laboratory , UniversityAmar Telidji, 3000 Laghouat, Algéria., Mechanics laboratory , University Amar Telidji, sans affiliation, Service d'hépatologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University of Waterloo, Waterloo, ON, Canada, Institute of Cell Biology and Immunology, University of Stuttgart, Chaperones Research Group, Institute of Biosciences and Technology [Houston, TX, États-Unis] (IBT), Texas A&M Health Science Center [Houston, TX, États-Unis] (TAMHSC), Texas A&M University Health Science Center-Texas A&M University Health Science Center, Aquatic and Crop Resource Development, National Research Council of Canada (NRC), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche [Ancona] (UNIVPM), Department of Biochemistry and Molecular Biology [Indianapolis, IN, USA], Indiana University School of Medicine, Indiana University System-Indiana University System, Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, iMed.UL, Faculty of Pharmacy, University of Lisbon, CESAM & Biology Department, Universidade de Aveiro, Celullar and Molecular Medicine, Università degli Studi di Perugia (UNIPG), Institute of Clinical Molecular Biology, Kiel University, Apoptose et Système Immunitaire (ASI), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematical Sciences [Aalborg], Aalborg University [Denmark] (AAU), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Biozentrum, University of Basel (Unibas), Structural and Computational Biology Unit, European Molecular Biology Laboratory [Grenoble] (EMBL), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Université de Perpignan Via Domitia (UPVD), Universidad Pablo de Olavide [Sevilla] (UPO), Department of Neurosciences, Agronomes et Vétérinaires Sans Frontières (AVSF), AVSF, Department of Mathematics [Gakushuin], Gakushuin University, Department of Internal Medicine [Münster, Germany], University of Münster, Neurogenetics laboratory, University Medicine Goettingen, Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université d'Uruguay, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Institute for Conservation & Improvement of Valentian Agrodiversity (COMAV), Universitat Politecnica de Valencia (UPV), ICBM, University of Chile [Santiago]-Faculty of Medicine, Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Department of Cell Biology, Baltimore, Johns Hopkins University School of Medicine, Baylor College of Medicine (BCM), Baylor University, University of Minnesota Medical School, Beijing Candid soft Technology Co. Ltd, Nanjing University of Information Science and Technology, Department of Hepatobiliary and Pancreatic Surgery [Maebashi, Japan], Gunma University Graduate Schoolof Medicine [Maebashi, Japan], Department of Molecular Genetics [Maastricht, The Netherlands], Maastricht University [The Netherlands], Institute of Cell Biology and Genetic Engineering, National Academy of Sciences of Ukraine (NASU), Institute of Pharmacology of Natural Products and Clinical Pharmacology, Institute of Pharmacology, University of Bern, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Wilmer Eye Institute, Mayo Clinic and Mayo College of Medicine, Rochester, Institute of Biochemistry and Biophysics, Polska Akademia Nauk (PAN)-Sciences, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Chemistry and Toxicology, Norwegian Veterinary Institute, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], University of Minho, Friedrich Miescher Laboratory (FML), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Biomedical Sciences and Biotechnologies, Brescia University, Department of Physiological Chemistry [Bochum], Ruhr-Universität Bochum [Bochum], University of Oslo (UiO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Facultés Universitaires Notre Dame de la Paix (FUNDP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226, Université du Québec à Montréal = University of Québec in Montréal (UQAM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Université Lille 2 - Faculté de Médecine -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Rio de Janeiro (UFRJ), Institut Bergonié [Bordeaux], UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), McGill University = Université McGill [Montréal, Canada], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Universidad de Chile = University of Chile [Santiago] (UCHILE), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISC), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Collège de France (CdF (institution)), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Hokkaido University [Sapporo, Japan], Université Paris sciences et lettres (PSL), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Lyon-Université de Lyon, Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), The Beatson Institute for Cancer Research, Beijing Normal University (BNU), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon], Vall d’Hebron Research Institute (VHIR), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Doshisha University [Kyoto], Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Università degli Studi di Firenze = University of Florence [Firenze], University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain], Central China Normal University [Wuhan, China], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie structurale [1992-2019] (IBS - UMR 5075 [1992-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nanjing University of Information Science and Technology (NUIST), Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de San Martin (UNSAM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, George Mason University [Fairfax]-Center for Applied Proteomics and Molecular Medicine, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institute of Infection, Immunity and Inflammation [Glasgow, UK]-University of Glasgow, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Settore BIO/06, biology, Cell Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, biology.organism_classification, Cell biology, Interpretation (model theory), 03 medical and health sciences, Arama, 030104 developmental biology, Molecular Biology, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; Arozena, AA; Adachi, H; Adams, CM; Adams, PD; Adeli, K; Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghiso, J; Airoldi, EM; Ait-Si-Ali, S; Akematsu, T; Akporiaye, ET; Al-Rubeai, M; Albaiceta, GM; Albanese, C; Albani, D; Albert, ML; Aldudo, J; Algul, H; Alirezaei, M; Alloza, I; Almasan, A; Almonte-Beceril, M; Alnemri, ES; Alonso, C; Altan-Bonnet, N; Altieri, DC; Alvarez, S; Alvarez-Erviti, L; Alves, S; Amadoro, G; Amano, A; Amantini, C; Ambrosio, S; Amelio, I; Amer, AO; Amessou, M; Amon, A; An, Z; Anania, FA; Andersen, SU; Andley, UP; Andreadi, CK; Andrieu-Abadie, N; Anel, A; Ann, DK; Anoopkumar-Dukie, S; Antonioli, M; Aoki, H; Apostolova, N; Aquila, S; Aquilano, K; Araki, K; Arama, E; Aranda, A; Araya, J; Arcaro, A; Arias, E; Arimoto, H; Ariosa, AR; Armstrong, JL; Arnould, T; Arsov, I; Asanuma, K; Askanas, V; Asselin, E; Atarashi, R; Atherton, SS; Atkin, JD; Attardi, LD; Auberger, P; Auburger, G; Aurelian, L; Autelli, R
Published: 2016
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76. The Influence of Modified Pluronic F127 Copolymers with Higher Phase Transition Temperature on Arsenic Trioxide-Releasing Properties and Toxicity in a Subcutaneous Model of Rats

Author: Yong Ma, Chi Zhang, Xiaoning Chen, Allan J. Easteal, Xueying Sun, Shangha Pan, and Hongchi Jiang
Subjects: Male, Silver, Chemistry, Pharmaceutical, Injections, Subcutaneous, Metal Nanoparticles, Pharmaceutical Science, Antineoplastic Agents, Poloxamer, Aquatic Science, Pharmaceutical formulation, Kidney, Arsenicals, Silver nanoparticle, chemistry.chemical_compound, Arsenic Trioxide, Drug Discovery, Animals, Technology, Pharmaceutical, Transition Temperature, Organic chemistry, Rats, Wistar, Arsenic trioxide, Ecology, Evolution, Behavior and Systematics, Drug Carriers, Ecology, Viscosity, Myocardium, Kidney metabolism, Heart, Hydrogels, Oxides, General Medicine, Rats, Liver, Solubility, chemistry, Drug delivery, Self-healing hydrogels, Rheology, Drug carrier, Oxidation-Reduction, Agronomy and Crop Science, Biomarkers, Research Article, Nuclear chemistry
Abstract: Pluronic F127 (PF-127) shows thermoreversible property, which is of the utmost interest in optimizing drug formulation and delivery. However, its hitherto unresolved drawback of a low phase transition temperature (T (tr)) has limited its application in injectable drug delivery systems. We have recently synthesized a new type of PF-127 copolymers with higher T (tr) using a simple oxidative method. Here, we have investigated the drug-releasing feature of oxidized PF-127 and oxidized PF-127-containing silver nanoparticles (SNPs), carrying arsenic trioxide (ATO), in a subcutaneous model of rats. Injectable hydrogels prepared with oxidized PF-127s were less viscous and easier to inject, at the same concentration, than their precursor. Addition of SNPs further elevated T (tr), resulting in even lower viscosity of the injectable hydrogel prepared from SNP-containing oxidized PF-127. The oxidized PF-127 copolymers did not differ significantly in ATO-releasing ability, compared with parental PF-127, but the addition of SNPs altered the ATO-releasing feature of oxidized PF-127 to some extent. ATO-carrying oxidized PF-127s had similar toxicity, but the addition of SNPs enhanced the hepatotoxicity of ATO, as evidenced by elevated serum levels of alanine aminotransferase and aspartate aminotransferase and histological alterations, compared to parental PF-127. The results presented herein warrant further investigation of the modified PF-127 copolymers to deliver ATO or other drugs in the form of injectable hydrogels.
Published: 2012
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77. Enhanced induction of heme oxygenase-1 suppresses thrombus formation and affects the protein C system in sepsis

Author: Shangha Pan, Yunpeng Luo, Xianglin Meng, Mingyan Zhao, Mingran Zhao, Geoffrey W. Krissansen, Xueying Sun, Hongchi Jiang, Chuanchuan Nan, Gang Tan, Dongsheng Fei, Kai Kang, and Wen Liu
Subjects: Male, Lipopolysaccharide, Thrombomodulin, Perforation (oil well), Protoporphyrins, Mice, chemistry.chemical_compound, Sepsis, Physiology (medical), Organometallic Compounds, medicine, Animals, Heme, Interleukin-6, Tumor Necrosis Factor-alpha, Biochemistry (medical), Public Health, Environmental and Occupational Health, Thrombosis, General Medicine, Molecular biology, Mice, Inbred C57BL, Heme oxygenase, Disease Models, Animal, chemistry, Biochemistry, Hemin, Tumor necrosis factor alpha, Heme Oxygenase-1, Protein C, medicine.drug
Abstract: Heme oxygenase-1 (HO-1) displays anti-inflammatory and cytoprotective activities in sepsis. Here, we investigated the effects of HO-1 on thrombus formation and the protein C system in a septic C57BL/6 mouse model induced by cecal ligation and perforation (CLP). Septic mice were either preinjected with the vehicle, pretreated with hemin (an HO-1 inducer) or zinc protoporphyrin IX (ZnPP, an HO-1 inhibitor), or given a combination of hemin + ZnPP. CLP increased significantly the hepatic expression of HO-1; increased thrombosis in livers, kidneys, and lungs; shortened the prothrombin time (PT) and activated partial thromboplastin time (APTT); elevated the levels of tumor necrosis factor-1α (TNF-1α), interleukin-6 (IL-6), and thrombomodulin (TM); reduced the levels of protein C (PC) and activated protein C (aPC); and downregulated hepatic expression of PC and TM. The preadministration of hemin to septic mice increased the expression and activity of HO-1; inhibited thrombosis in the preceding 3 organs; prolonged PT and APTT; inhibited the production of TNF-α and IL-6; upregulated the expression of PC and TM in livers; elevated the plasma levels of PC and aPC; and reduced the plasma levels of TM. In contrast, ZnPP showed opposite effects to hemin and reversed the effects of hemin by inhibiting the activity of HO-1. The administration of tricarbonyl dichloro ruthenium (II) dimer (CORM-2), which is a CO-releasing molecule, had a similar effect to hemin on thrombosis and the protein C system. The data indicate that the enhanced induction of HO-1 inhibits thrombus formation and affects the protein C system in sepsis.
Published: 2012
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78. Matrine Inhibits Breast Cancer Growth ViamiR-21/PTEN/AktPathway in MCF-7 Cells

Author: Hongli Shan, Haihai Liang, Lu Wang, Rui Guo, Weijie Du, Yanjie Lu, Linqiang Li, Hongchi Jiang, Xuelian Li, Desen Liang, and Xue Liu
Subjects: Cyclin-Dependent Kinase Inhibitor p21, Cell Survival, Physiology, Down-Regulation, Apoptosis, Breast Neoplasms, chemistry.chemical_compound, Alkaloids, Matrine, Humans, Medicine, PTEN, Viability assay, Matrines, Protein kinase B, PI3K/AKT/mTOR pathway, biology, business.industry, Cell growth, PTEN Phosphohydrolase, Cell cycle, G1 Phase Cell Cycle Checkpoints, Molecular biology, Up-Regulation, MicroRNAs, MCF-7, chemistry, S Phase Cell Cycle Checkpoints, MCF-7 Cells, biology.protein, Female, bcl-Associated Death Protein, business, Proto-Oncogene Proteins c-akt, Cyclin-Dependent Kinase Inhibitor p27, Quinolizines, Signal Transduction
Abstract: Background: Matrine is one of the major alkaloids extracted from Sophora flavescens and has been used clinically for breast cancer with notable therapeutic efficacy in China. However, the mechanisms are still largely unknown. Methods: Cell viability was analyzed by MTT assay. After MCF-7 cells were treated with matrine for 48h, apoptosis was detected by flow cytometry, TUNEL assay and transmission electron microscopy, and the cell cycle distribution was also analyzed by flow cytometry. Further, the expression of PTEN, pAkt, Akt, pBad, Bad, p21/WAF1/CIP1 , and p27/KIP1 was determined by Western blot. Changes of miR-21 level were quantified by real-time RT-PCR. After miR-21 was transfected in MCF-7 cells, PTEN protein level was measured by Western blot. Results: Matrine inhibited MCF-7 cell growth in a concentration-and time-dependent manner, by inducing apoptosis and cell cycle arrest at G1/S phase. Matrine up-regulated PTEN by downregulating miR-21 which in turn dephosphorylated Akt, resulting in accumulation of Bad, p21/WAF1/CIP1 and p27/KIP1. Conclusion: Our study unraveled, for the first time, the ability of matrine to suppress breast cancer growth and elucidated the miR-21/PTEN/Akt pathway as a signaling mechanism for the anti-cancer action of matrine. Our findings also reinforce the notion that miRNAs can act as mediators of the therapeutic efficacy of natural medicines.
Published: 2012
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79. Overexpression of von Hippel–Lindau protein synergizes with doxorubicin to suppress hepatocellular carcinoma in mice

Author: Jizhou Wang, Yong Ma, Geoffrey W. Krissansen, Shangha Pan, Lianxin Liu, Xueying Sun, Hongchi Jiang, Bei Sun, and Huaqiang Zhu
Subjects: Male, Cell cycle checkpoint, Angiogenesis, Down-Regulation, Gene Expression, Antineoplastic Agents, Apoptosis, Biology, urologic and male genital diseases, medicine.disease_cause, Mice, chemistry.chemical_compound, Liver Neoplasms, Experimental, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, medicine, Animals, Doxorubicin, neoplasms, Cell Proliferation, Neovascularization, Pathologic, Hepatology, Cell growth, NF-kappa B, Hypoxia-Inducible Factor 1, alpha Subunit, Combined Modality Therapy, Recombinant Proteins, female genital diseases and pregnancy complications, Mice, Inbred C57BL, Vascular endothelial growth factor, Hypoxia-inducible factors, chemistry, Von Hippel-Lindau Tumor Suppressor Protein, Cancer research, Carcinogenesis, medicine.drug
Abstract: Background & Aims Hypoxia-inducible factors (HIFs) and nuclear factor-κB (NF-κB) regulate genes involved in carcinogenesis and progression of cancers including hepatocellular carcinoma (HCC). The von Hippel–Lindau (VHL) protein (pVHL) targets HIFα subunits for destruction and participates in modulating the activity of NF-κB. The present study aimed to investigate whether the overexpression of pVHL synergizes with doxorubicin in the treatment of HCC. Methods Overexpression of pVHL was induced by infecting mouse HCC Hepa1–6 and H22 cells, or injecting subcutaneous Hepa1–6 tumors in C57BL/c mice, with adenoviral vectors encoding mouse VHL gene. Cell proliferation, apoptosis, tumoral angiogenesis, and gene expression and DNA-binding activity of NF-κB were examined. The therapeutic effects of pVHL were also evaluated in orthotopic Hepa1–6 tumors by intraportal delivery of Ad-VHL. Results Ad-VHL enhanced the anti-tumor activity of doxorubicin by inhibiting cell proliferation, and causing cell cycle arrest and apoptosis. The Ad-VHL infection downregulated HIF-1α and HIF-2α expression, and inhibited NF-κB activity and the expression of genes involved in apoptosis, proliferation, angiogenesis, invasion, and metastasis. Injection of Ad-VHL into HCC tumors augmented doxorubicin-induced suppression of tumor growth by inhibiting cell proliferation and tumor angiogenesis, and by inducing cell apoptosis. Effects on the expression of HIFαs, activity of NF-κB, and their downstream genes were in accordance with the in vitro findings. Intraportal injection of Ad-VHL enhanced the efficacy of doxorubicin to suppress the growth of orthotopic liver tumors. Conclusions By targeting HIF and NF-κB, overexpression of pVHL enhances the efficacy of doxorubicin, and warrants consideration as a potential therapeutic strategy for treating HCC.
Published: 2011
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80. Matrine attenuates endotoxin-induced acute liver injury after hepatic ischemia/reperfusion in rats

Author: Feng Zhang, Haiquan Qiao, Liguang You, Xueying Sun, Xinlei Li, Hongchi Jiang, Liquan Tong, and Xun Wang
Subjects: Lipopolysaccharides, Male, Necrosis, Pharmacology, Fas ligand, Nitric oxide, chemistry.chemical_compound, Alkaloids, Matrine, medicine, Animals, Rats, Wistar, Matrines, Liver injury, business.industry, Liver Diseases, General Medicine, medicine.disease, Endotoxemia, Rats, Disease Models, Animal, chemistry, Apoptosis, Reperfusion Injury, Immunology, Surgery, Tumor necrosis factor alpha, medicine.symptom, business, Reperfusion injury, Quinolizines
Abstract: Hepatic ischemia/reperfusion (HIR) injury is an unavoidable consequence of major liver surgery, during which endotoxemia often takes place. This study aimed to investigate whether matrine has a protective effect against HIR-induced liver injury aggravated by endotoxin. Wistar rats were subjected to 30 min of HIR followed by lipopolysaccharide (LPS) (0.5 mg/kg) administration. At the indicated time points, six rats from each group (24 rats) were randomly euthanized to collect blood samples and livers. Preadministration of matrine protected livers from injury induced by HIR+LPS as the histological score, myeloperoxidase activity and malondialdehyde contents, expression of macrophage-inflammatory protein-2, DNA-binding activity of nuclear factor κB, and serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, and nitric oxide were significantly reduced, and serum levels of interleukin-6 were further increased. HIR+LPS markedly induced cell apoptosis and necrosis, and upregulated the expression of cleaved caspase-3, Fas, and FasL. Matrine significantly reduced cell necrosis, but had a nonsignificant inhibitory effect on cell apoptosis and expression of cleaved caspase-3 and FasL Matrine attenuates endotoxin-induced acute liver injury after HIR mainly by its anti-inflammatory and antioxidative activities, and has little inhibitory effect on cell apoptosis.
Published: 2011
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81. Pretreatment with Bilirubin Protects Islet against Oxidative Injury During Isolation and Purification

Author: Jizhou Wang, Q.Z. Kong, Wenjie Dai, Hongchi Jiang, Yong Ma, Yue Gao, Shangha Pan, H.R. Guo, and Huaqiang Zhu
Subjects: Male, endocrine system, endocrine system diseases, Cell Survival, Bilirubin, Pharmacology, Biology, medicine.disease_cause, Lipid peroxidation, Islets of Langerhans, chemistry.chemical_compound, Malondialdehyde, medicine, Animals, Propidium iodide, Rats, Wistar, Transplantation, geography, geography.geographical_feature_category, Acridine orange, Islet, Rats, Oxidative Stress, chemistry, Biochemistry, Surgery, Lipid Peroxidation, Oxidative stress
Abstract: Background A high yield of pure, viable islets is one of the most important prerequisites for successful islet transplantation. However, during isolation and purification, many factors may cause oxidative stress, impacting islet viability. Accumulating evidence indicates that bilirubin (BR) not only has antioxidative but also has cytoprotective activities. In this study, we investigated whether pretreatment with bilirubin would protect islets against oxidative damage during isolation and purification. Methods Wistar rats were randomly divided into control and BR groups. The latter rats received an injection of BR 2 hours before islet isolation, whereas the controls received vehicle. Islet purity was determined using a dithizone stain. Survival rate and viability were determined using acridine orange and propidium iodide staining and the Cell Counting Kit-8 Kit. Islet function was quantified by testing glucose-stimulated insulin secretion. Islet damage caused by oxidative stress was quantified by measuring the malondialdehyde (MDA) in freshly isolated islets. Results Pretreatment with bilirubin did not enhance the purity, but significantly enhanced the survival rate and viability of the islets. Islet function in the BR group was significantly better than that in the control cohort. The MDA level was 0.62 ± 0.23 nmol/L/μg protein in the BR group, which was significantly lower (P Conclusions We concluded that oxidative stress during islet isolation and purification can be mitigated by BR pretreatment. BR exerts antioxidant and cytoprotective properties by reducing lipid peroxidation (MDA) and enhancing islet viability and function. Pretreatment with BR may become a simple, clinical applicable means to improve human islet isolation and transplantation outcomes.
Published: 2011
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82. Hippo signaling in oval cells and hepatocarcinogenesis

Author: Hongchi Jiang, Tongsen Zheng, Lianxin Liu, and Jiabei Wang
Subjects: Cancer Research, Hippo signaling pathway, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Liver tumor, Stem Cells, Liver Neoplasms, Protein Serine-Threonine Kinases, Biology, medicine.disease, medicine.disease_cause, Models, Biological, Oncology, Hippo signaling, medicine, Cancer research, Humans, Stem cell, Signal transduction, Liver cancer, Cell activation, Carcinogenesis, Signal Transduction
Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer mortality world wide. Despite continuing development of new therapies, the prognosis for patients with HCC remains extremely poor. In part, this may relate to molecular abnormalities that stimulate HCC tumorigenesis and also contribute to reduced sensitivity to standard treatment. Increasing evidence has revealed the importance of liver cancer stem cells in hepatocarcinogenesis. Although widely investigated, the signaling pathways important for liver cancer stem cells in liver tumor initiation and progression are poorly understood. The Hippo signaling pathway was identified in Drosophila as an essential regulator of cell proliferation and apoptosis. Recently, Hippo pathway has been implicated in multiple events during development and it has also been proposed to play a vital role in several tumor types, especially in hepatocellular carcinoma. Strong evidences also proved the significant role of the Hippo signaling pathway in oval cell activation. As suggested, hippo signaling has a dual regulation of Hippo in liver tumor suppression as well as transition of oval cells to fully differentiated hepatocytes. Delineation of the malfunction of Hippo signaling pathway in HCC may lead to better understanding of hepatocarcinogenesis, rational medical therapy for HCC and possible therapy for other tumors. Here, we provide a historical review of this potent growth-regulatory pathway in HCC and highlight outstanding questions that will likely be the focus of future investigation.
Published: 2011
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83. Genistein potentiates the effect of arsenic trioxide against human hepatocellular carcinoma: Role of Akt and nuclear factor-κB

Author: Xueying Sun, Hongchi Jiang, Lianxin Liu, Jizhou Wang, Xiaoning Chen, Yong Ma, Shangha Pan, and Huaqiang Zhu
Subjects: Cancer Research, Carcinoma, Hepatocellular, Angiogenesis, Genistein, Antineoplastic Agents, Apoptosis, Arsenicals, Mice, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Cyclin D1, Arsenic Trioxide, In vivo, Animals, Humans, Arsenic trioxide, Protein kinase B, Cell Proliferation, Chemistry, Cell Cycle, Liver Neoplasms, NF-kappa B, Drug Synergism, Oxides, Hep G2 Cells, Xenograft Model Antitumor Assays, Vascular endothelial growth factor, Oncology, Immunology, Cancer research, Proto-Oncogene Proteins c-akt
Abstract: Hepatocellular carcinoma (HCC) is a highly lethal malignancy mostly because of de novo and acquired resistance to conventional chemotherapy. Constitutive activation of Akt and nuclear factor-κB (NF-κB) represent major cellular abnormalities associated with both the pathogenesis and therapeutic resistance of HCC. The aim of the present study was to determine whether genistein, a natural Akt/NF-κB inhibitor, could enhance the anti-HCC efficacy of ATO both in vitro and in vivo. Our results demonstrated that genistein not only potentiated the proliferation-inhibiting and apoptosis-inducing effect of ATO on human HCC cell lines in vitro, but also dramatically augmented its suppressive effect on both tumor growth and angiogenesis in nude mice. The mechanism is at least partially due to the suppressive effect of genistein both on the proper and ATO-induced Akt activation, and on the activity of NF-κB, and the latter correlated with the suppression of NF-κB regulated gene products, including cyclin D1, Bcl-xL, Bcl-2, c-myc, COX-2, and VEGF. These data suggest that the combination of ATO with genistein presents a promising therapeutic approach for the treatment of HCC.
Published: 2011
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84. MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro

Author: Lianxin Liu, Hongchi Jiang, Nishant Bhatta, Jiabei Wang, Xianzhi Meng, Shangha Pan, Xi Chen, Xuan Song, and Tongsen Zheng
Subjects: Hepatology, medicine.diagnostic_test, Cell growth, Gastroenterology, Biology, medicine.disease, digestive system diseases, Flow cytometry, Blot, Apoptosis, Cell culture, Hepatocellular carcinoma, medicine, Cancer research, Carcinoma, Viability assay, neoplasms
Abstract: Background and Aims: Nutlin-3, a selective small-molecule inhibitor of the p53-MDM2 interaction, has been shown to have antitumor activities in various tumors with wild-type p53. However, its effect on hepatocellular carcinoma (HCC) with different types of p53 remains unclear. This study is designed to determine nutlin-3′s antitumor efficacy and underlying mechanisms of action in human HCC cells. Methods: Cell viability assay, cell cycle analysis, apoptosis assay, western blot, co- immunoprecipitation and siRNA experiments were analyzed in three human HCC cells. Anti-tumoral effects of nutlin-3 targeting the p53 and p73 pathways were evaluated in HCC cell lines. Results: Nutlin-3 exerted the greatest anti-tumoral effect to three human HCC cells with wild-type p53, mutant p53 and p53-null. Nutlin-3 not only upregulated p53 in HepG2 cells, but also p73 in Huh7 and Hep3B cells, and disrupted p53-MDM2 and p73-MDM2 complexes in HCC cells. The compound inhibited cell proliferation, induced G0/G1 phase arrest, decreased the levels of CyclinD1, CyclinE, CDK2, CDK4, PCNA and E2F-1, and increased the levels of p21 and p27. It also induced apoptosis, increased the Bax/Bcl-2 ratio, then activated caspase-9 and caspase-3. Conclusions: Nutlin-3 has significant anticancer effects against human HCC cells, regardless of p53 status, indicating that it is a promising therapy for human hepatocellular carcinoma.
Published: 2011
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85. microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells

Author: Lianxin Liu, Jiabei Wang, Shangha Pan, Tongsen Zheng, Xi Chen, Hongchi Jiang, Wei-Hui Zhang, and Xianzhi Meng
Subjects: Regulation of gene expression, Hepatology, medicine.diagnostic_test, Cell growth, Gastroenterology, Transfection, Biology, Molecular biology, Flow cytometry, Gene expression profiling, chemistry.chemical_compound, chemistry, microRNA, medicine, Viability assay, Arsenic trioxide
Abstract: Background and Aim: More and more microRNA (miRNA) are found to be involved in tumor genesis and progress. Arsenic trioxide has been an effective chemotherapeutic drug in cancer therapy for many years. In this study, we aimed to find the miRNA involved in the mechanisms of arsenic trioxide treatment in cancer therapy. Methods: We detected the expression profile of miRNA by miRNA microarray and quantitative real-time polymerase chain reaction. Cell viability assay, flow cytometry analysis, prediction of miRNA targets, Western blot analysis and luciferase reporter assay were carried out to determine the role of one selected miRNA, namely mir-29a, in affecting the biological behaviors of HepG-2 cells. Results: Among the 677 human miRNA in the microarray, five miRNA were upregulated and four were downregulated in HepG-2 cells treated with arsenic trioxide compared to their controls. If only changes above two folds were considered, four miRNA were identified, namely miR-24, miR-29a, miR-30a and miR-210, which were all upregulated. Among them, miR-29a showed a positive therapeutic effect in liver cancer cells by inhibiting cell growth and inducing cell apoptosis, and PPM1D was confirmed to be the target gene of miR-29a. Furthermore, a synergy effect was detected between miR-29a and arsenic trioxide. Conclusions: Arsenic trioxide altered miRNA expression profile in HepG-2 cells. Among the altered miRNA, miR-29a seemed to take a role in the mechanism of arsenic trioxide in liver cancer therapy. The synergy effect between miR-29a and arsenic trioxide may offer this drug a new chance in cancer therapy by decreasing its dose and toxic side-effects.
Published: 2010
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86. Indications and procedures for second-look surgery in acute mesenteric ischemia

Author: Lianxin Liu, Hongchi Jiang, and Xianzhi Meng
Subjects: Reoperation, medicine.medical_specialty, medicine.medical_treatment, Infarction, Extent of resection, Endoscopy, Gastrointestinal, Acute mesenteric ischemia, Ischemia, Risk Factors, Laparotomy, Mesenteric Vascular Occlusion, medicine, Second Look Surgery, Humans, Mesentery, Laparoscopy, medicine.diagnostic_test, business.industry, General surgery, General Medicine, Bowel resection, medicine.disease, Mesenteric Arteries, Surgery, Endoscopy, Intestines, Intestinal Diseases, Second-Look Surgery, Acute Disease, business
Abstract: Acute mesenteric ischemia (AMI) is a highly lethal clinical entity associated with high morbidity and mortality. Bowel necrosis often results, usually necessitating bowel resection; however, deciding on the extent of resection is problematic as accurate identification of ischemic bowel that may undergo subsequent infarction is difficult. Therefore, a second-look laparotomy after the first operation is usually recommended. While the second-look procedure is widely accepted, its optimal indications and mode are still controversial, raising questions such as "second-look or not?," "planned relaparotomy or relaparotomy on demand?," and "open or laparoscopic?" In this review we discuss the relevant literature and reassess the role of the second-look operation in the treatment of AMI.
Published: 2010
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87. PTEN- and p53-mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice

Author: Xianzhi Meng, Shangha Pan, Dalong Yin, Yingjian Liang, Xuan Song, Lianxin Liu, Hongchi Jiang, Jiabei Wang, Tongsen Zheng, and Xi Chen
Subjects: Cell cycle checkpoint, Mice, Nude, Antineoplastic Agents, Apoptosis, Cell Cycle Proteins, Biology, Biochemistry, Mice, Phosphatidylinositol 3-Kinases, Sphingosine, Stomach Neoplasms, Cell Line, Tumor, hemic and lymphatic diseases, medicine, Animals, Humans, PTEN, RNA, Small Interfering, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cisplatin, Mice, Inbred BALB C, Fingolimod Hydrochloride, Cell growth, G1 Phase, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-mdm2, Cell Biology, Propylene Glycols, Cancer cell, biology.protein, Cancer research, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-akt, Immunosuppressive Agents, Neoplasm Transplantation, Signal Transduction, medicine.drug
Abstract: FTY720, a new immunosuppressant, derived from ISP-1, has been studied for its putative anti-cancer properties in the recent years. In this study, we have reported that FTY720 greatly inhibited gastric cancer cell proliferation for the first time, and found this effect was associated with G1 phase cell cycle arrest and apoptosis. Results from our Western blotting and Real-time PCR showed that FTY720 induced obvious PTEN expression in a p53-independent way, consistent with a substantial decrease in p-Akt and MDM2. FTY720 dramatically increased the expression of Cip1/p21, p27, and BH3-only proteins through the accumulation of p53 by PTEN-mediated inhibition of the PI3K/Akt/MDM2 signaling. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt, resulting in decreased apoptosis and increased cell survival. Furthermore, we have observed an additive effect of FTY720 in killing gastric cancer cells when in combination with Cisplatin, partly through PTEN-mediated Akt/MDM2 inhibition. In vivo study has also shown that tumor growth was significantly suppressed after FTY720 treatment. In conclusion, our results suggest that FTY720 induces a significant increase of PTEN, which inhibits p-Akt and MDM2, and then increases the level of p53, thereby inducing G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, for the first time, which shows potential anti-tumor effects on gastric cancer by PTEN activation through p53-independent mechanism, especially in combination with Cisplatin. This PTEN target-based therapy is worth further investigation and warrants clinical evaluation.
Published: 2010
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88. Disruption of p73-MDM2 binding synergizes with gemcitabine to induce apoptosis in HuCCT1 cholangiocarcinoma cell line with p53 mutation

Author: Lianxin Liu, Tongsen Zheng, Jiabei Wang, Xianzhi Meng, Xuan Song, Hongchi Jiang, Xi Chen, and Zhaoyang Lu
Subjects: Antimetabolites, Antineoplastic, Small interfering RNA, Blotting, Western, Apoptosis, Deoxycytidine, Piperazines, Cholangiocarcinoma, Tumor Cells, Cultured, medicine, Humans, Immunoprecipitation, RNA, Messenger, RNA, Small Interfering, neoplasms, Caspase, Cell Proliferation, biology, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, Tumor Suppressor Proteins, Imidazoles, Nuclear Proteins, Drug Synergism, Proto-Oncogene Proteins c-mdm2, Tumor Protein p73, General Medicine, Gemcitabine, DNA-Binding Proteins, Blot, Bile Duct Neoplasms, Cell culture, Mutation, biology.protein, Cancer research, Mdm2, Drug Therapy, Combination, Tumor Suppressor Protein p53, medicine.drug
Abstract: Chemotherapy to date has not been effective in the treatment of cholangiocarcinoma. However, gemcitabine, a novel nucleoside analog, has shown remarkable biological activity against cholangiocarcinoma in some clinical studies. Combinations of gemcitabine with other agents have also shown promising results, with a tolerable toxicity profile. Nutlin-3 is a small-molecule inhibitor that acts to inhibit murine double minute-2 (MDM2) binding to p53 or p73 and subsequently activates p53- or p73-dependent apoptosis signaling pathways. To investigate their effects in combination, a p53-mutant cholangiocarcinoma line HuCCT1 was treated with Nutlin-3 and/or gemcitabine in the current study. Cell proliferation assay, apoptosis assay, Western blot, coimmunoprecipitation, and small interfering RNA (siRNA) experiments were analyzed in HuCCT1 cells. Antitumoral effects of Nutlin-3 and/or gemcitabine targeting the p73/MDM2 pathways were evaluated. Nutlin-3 and gemcitabine can both inhibit the growth of HuCCT1 cells. Nutlin-3 induces apoptosis and potentiates the cytotoxic effect of gemcitabine through disrupting the binding of p73 with MDM2. Nutlin-3 leads to activation of caspases, increase levels of puma and bax, and decrease the expression of bcl-2. Blocking p73 function with a siRNA attenuates the apoptosis induced by gemcitabine, Nutlin-3, and gemcitabine/Nutlin-3 combination. Our data provide evidence that p73 might compensate for p53 function in gemcitabine-induced apoptosis of HuCCT1 cells. Nutlin-3 acts through the inhibition of p73-MDM2 with subsequent activation of the apoptotic pathway signaling, which leads to the increase in chemosensitivity to gemcitabine. In summary, our findings suggest that Nutlin-3 will be active in the treatment of p53-mutant cholangiocarcinoma, especially when in combination with gemcitabine.
Published: 2010
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89. Nutlin-3 cooperates with doxorubicin to induce apoptosis of human hepatocellular carcinoma cells through p53 or p73 signaling pathways

Author: Jiabei Wang, Xuan Song, Tongsen Zheng, Lianxin Liu, Hongchi Jiang, Xianzhi Meng, and Shangha Pan
Subjects: Cancer Research, Carcinoma, Hepatocellular, Tumor suppressor gene, medicine.medical_treatment, Cell, Apoptosis, Piperazines, chemistry.chemical_compound, Cell Line, Tumor, medicine, Humans, Doxorubicin, RNA, Small Interfering, neoplasms, Chemotherapy, Antibiotics, Antineoplastic, biology, Tumor Suppressor Proteins, Liver Neoplasms, Imidazoles, Nuclear Proteins, Drug Synergism, Proto-Oncogene Proteins c-mdm2, Tumor Protein p73, General Medicine, Nutlin, medicine.disease, digestive system diseases, DNA-Binding Proteins, medicine.anatomical_structure, Oncology, chemistry, biology.protein, Cancer research, Mdm2, Tumor Suppressor Protein p53, Liver cancer, Signal Transduction, medicine.drug
Abstract: Despite recent advances in chemotherapeutic agents for Hepatocellular carcinoma (HCC) treatment, the results of chemotherapy remain unsatisfactory. Doxorubicin (DOX) still represents the cornerstone in HCC chemotherapy, but resistance and toxicity to normal cells are major obstacles to successful chemotherapy. Therefore, new active agents in HCC chemotherapy and agents that increase the chemosensitivity of HCC cells to DOX are still urgently required. Nutlin-3 is a small-molecule inhibitor that acts to inhibit murine double minute-2 (MDM2) binding to p53 or p73, and subsequently activates p53- or p73-dependent apoptosis signaling pathway. This study was designed to investigate whether Nutlin-3 alters cell toxicity to HCC cells following DNA damage and to assess the suitability of DOX/Nutlin-3 as a chemotherapeutic combination in HCC chemotherapy.Four human HCC cells were analyzed using cell proliferation assay, apoptosis assay, western blotting, co-immunoprecipitation and siRNA experiments. Anti-tumoral effects of Nutlin-3/DOX targeting the p53/MDM2 and p73/MDM2 pathways were evaluated in HCC cell lines.Nutlin-3 enhances the growth inhibition by DOX and potentates the apoptotic effect in all HCC cell lines with different p53 types. Nutlin-3 acts through the disruption of p53-MDM2 binding in HepG2, and the disruption of p73-MDM2 in Huh-7 and Hep3B cell lines with subsequent activation of the apoptotic pathway, which leads to the increase in chemosensitivity to DOX in HCC cells.Taken together, our findings suggest that Nutlin-3 will be active in the treatment of HCC and offers new prospects for overcoming DOX resistance.
Published: 2010
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90. Genistein synergizes with arsenic trioxide to suppress human hepatocellular carcinoma

Author: Xueying Sun, Hongchi Jiang, Xiaoning Chen, Bei Sun, Geoffrey W. Krissansen, Yong Ma, and Shangha Pan
Subjects: Male, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Cell Survival, Mice, Nude, Genistein, Apoptosis, Arsenicals, Mice, chemistry.chemical_compound, Arsenic Trioxide, Cell Line, Tumor, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Animals, Humans, Viability assay, Arsenic trioxide, chemistry.chemical_classification, Reactive oxygen species, biology, Chemistry, Cell growth, Cytochrome c, Liver Neoplasms, Drug Synergism, Oxides, General Medicine, Xenograft Model Antitumor Assays, Caspase 9, Endocrinology, Oncology, Cancer research, biology.protein, Butylated hydroxyanisole, Reactive Oxygen Species
Abstract: Arsenic trioxide (ATO) is of limited therapeutic benefit for the treatment of solid tumors. Genistein exhibits anticancer and pro-oxidant activities, making it a potential candidate to enhance the efficacy of ATO whose cytotoxicity is oxidation-sensitive. This study sought to determine whether genistein synergizes with ATO to combat hepatocellular carcinoma (HCC). Three human HCC cell lines, namely HepG2, Hep3B, and SK-Hep-1, were incubated with ATO, genistein, or ATO + genistein. The cells were also pretreated with antioxidant agents N-acetyl-L-cysteine (NAC) or butylated hydroxyanisole (BHA). Cell viability, apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (DeltaPsim), expression of Bcl-2, Bax, caspase-9, and -3, and release of cytochrome c into the cytosol were examined. The synergistic effect of ATO and genistein was also assessed using HepG2 xenografts subcutaneously established in BALB/c nude mice. The results show that genistein synergized with ATO to reduce viability, induce apoptosis, and diminish the DeltaPsim of cells. The combination therapy down-regulated Bcl-2 expression, up-regulated Bax expression, enhanced the activation of caspase-9 and -3, and increased the release of cytochrome c. The synergistic effect of ATO and genistein was diminished by pretreatment with NAC or BHA. Genistein increased the production of intracellular ROS, while ATO had little effect. Genistein synergized with a low dose of ATO (2.5 mg/kg) to significantly inhibit the growth of HepG2 tumors, and suppress cell proliferation and induce apoptosis in situ. There were no obvious side effects, as seen with a high dose of ATO (5 mg/kg). Combining genistein with ATO warrants investigation as a therapeutic strategy to combat HCC.
Published: 2009
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91. Role of hydrogen sulfide in hepatic ischemia-reperfusion-induced injury in rats

Author: Gang Tan, Mingyan Zhao, Kai Kang, Xueying Sun, Hongchi Jiang, and Shangha Pan
Subjects: Liver injury, Transplantation, medicine.medical_specialty, Hepatology, biology, business.industry, Sodium hydrosulfide, equipment and supplies, medicine.disease, Cystathionine beta synthase, Fas ligand, Nitric oxide, Lipid peroxidation, chemistry.chemical_compound, Endocrinology, Biochemistry, chemistry, Apoptosis, Internal medicine, medicine, biology.protein, Surgery, Tumor necrosis factor alpha, business
Abstract: Hydrogen sulfide (H2S) displays anti-inflammatory and cytoprotective activities as evidenced by the inhibition of myocardial ischemia-reperfusion injury and production of lipid peroxidation. H2S also exerts many physiological or pathological effects on livers. Therefore, we designed the present study to investigate the roles of H2S in hepatic ischemia-reperfusion (HIR)-induced injury in rats by measuring H2S levels, H2S synthesizing activity, and cystathionine gamma-lyase (CSE) messenger RNA (mRNA) expression. We also applied DL-propargyl glycine (PAG) and sodium hydrosulfide (NaHS) to investigate their effects on the severity of liver injury induced by HIR. The levels of H2S, H2S production activity, and CSE mRNA expression in livers were increased by HIR. Administration of NaHS significantly attenuated the severity of liver injury and inhibited the production of lipid peroxidation, serum inflammatory factors [including nitric oxide, tumor necrosis factor alpha (TNF-alpha), interleukin 10, and intercellular cell adhesion molecule 1], cell apoptosis, and apoptosis-related proteins (including caspase-3, Fas, Fas ligand, and TNF-alpha), which were caused or elevated by HIR, whereas PAG aggravated them. However, NaHS or PAG did not show significant effects on the activation of caspase-9, which was also increased by HIR. Although further investigation is required, this study may indicate that H2S plays a protective role in HIR-induced injury.
Published: 2009
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92. Role of the Spleen in Cyclophosphamide-induced Hematosuppression and Extramedullary Hematopoiesis in Mice

Author: Qinggang Meng, Yuli Wang, Haiquan Qiao, Xueying Sun, and Hongchi Jiang
Subjects: Male, Pathology, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Splenectomy, CD34, Antigens, CD34, Cell Count, Spleen, Flow cytometry, Andrology, Mice, medicine, Animals, Progenitor cell, Antineoplastic Agents, Alkylating, Mice, Inbred BALB C, medicine.diagnostic_test, business.industry, General Medicine, Hematopoietic Stem Cells, medicine.disease, Hematopoiesis, Extramedullary hematopoiesis, Proto-Oncogene Proteins c-kit, Haematopoiesis, medicine.anatomical_structure, Hematopoiesis, Extramedullary, business, medicine.drug
Abstract: Background and Aims Extramedullary hematopoiesis (EMH) is induced in spleens due to various diseases. The aim of this study is to investigate the role of spleen in cyclophosphamide (CTX)-induced hematosuppression and EMH in mice. Methods Balb/c mice were IP injected with 300 mg/kg CTX 2 weeks after splenectomy or sham operation and randomly sacrificed 1, 3, 7, 14, and 21 days after injection. Blood samples were collected, and spleens were weighed, histologically analyzed, and then used for flow cytometry. Results There were significant differences in white blood count, red blood count, platelet numbers and hemoglobin concentration between the splenectomized and sham-operated mice after CTX injection. The cellularity of the spleen was reduced 3 days following CTX treatment but then rose 7 days after CTX treatment. The numbers of colony-forming units in the spleen reached a peak 7 days after CTX injection, then declined. Flow cytometry demonstrated the percentage of CD34 + and CD117 + cells in the spleen increased 7 days after CTX injection, indicating the hematopoietic stem and progenitor cells in the spleen. Conclusions The study indicates that EMH occurs as a compensatory reaction to CTX-induced hematosuppression in the murine spleen, implying that conservation of the spleen may promote the recovery of cancer patients from chemotherapy-induced hematosuppression.
Published: 2009
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93. Adeno-associated virus-mediated expression of kallistatin suppresses local and remote hepatocellular carcinomas

Author: Xuesong Dong, Ruian Xu, Xueying Sun, Hongchi Jiang, Farzin Farzaneh, Peter W.C. Fung, and Lai Yin Tse
Subjects: Male, Carcinoma, Hepatocellular, Angiogenesis, viruses, Genetic enhancement, Apoptosis, medicine.disease_cause, Mice, Transduction, Genetic, Cell Line, Tumor, Drug Discovery, Genetics, medicine, Animals, Humans, Molecular Biology, Adeno-associated virus, Serpins, Genetics (clinical), Cell Proliferation, Mice, Inbred BALB C, business.industry, Genetic Therapy, Transfection, Dependovirus, medicine.disease, digestive system diseases, Angiogenesis inhibitor, Kallistatin, Hepatocellular carcinoma, Immunology, Cancer research, Molecular Medicine, business
Abstract: Background The current treatments for hepatocellular carcinoma (HCC) are poor, particularly for metastatic HCC. Intraportal transfusion of adeno-associated virus (AAV) leads to long-term and persistent transgenic expression in livers. Kallistatin, a novel angiogenesis inhibitor, exhibits anti-tumor activity. The aim of the study was to investigate whether intraportal injection of AAV-kallistatin could suppress local and metastatic HCC in mice. Methods An AAV vector encoding kallistatin was constructed, and its transduction efficiency by intraportal transfusion in livers was examined by RT-PCR, immunohistochemical and Western blotting analysis. The anti-tumor activity was tested in three HCC models including hepatic and subcutaneous human Hep3B HCC tumors in BALB/c athymic (nu/nu) mice, and subcutaneous mouse BNL HCC tumors in BALB/c mice. Tumor cell proliferation in situ was examined by anti-Ki-67 staining, and apoptosis by TUNEL. Results Gene transfection by rAAV-kallistatin inhibited proliferation of human umbilical vein endothelial cells and HCC cells in vitro. Intraportal injection of rAAV-kallistatin resulted in persistent and specific expression of kallistatin in livers detected by RT-PCR and immunohistochemical analysis, and kallistatin protein in circulation detected by Western blotting analysis. Intraportal injection of rAAV-kallistatin significantly suppressed angiogenesis and growth of hepatic Hep3B tumors. The kallistatin released by hepatocytes into the circulation suppressed remote Hep3B and BNL tumors established subcutaneously. The rAAV-kallistatin gene therapy significantly inhibited tumor cell proliferation and induced apoptosis. Conclusions Intraportal injection of rAAV-kallistatin suppressed hepatic and subcutaneous HCC tumors, relying on its anti-angiogenic and anti-proliferative activities. Copyright © 2008 John Wiley & Sons, Ltd.
Published: 2008
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94. N-myc downstream-regulated gene 2 inhibits human cholangiocarcinoma progression and is regulated by leukemia inhibitory factor/MicroRNA-181c negative feedback pathway

Author: Jiabei, Wang, Changming, Xie, Shangha, Pan, Yingjian, Liang, Jihua, Han, Yaliang, Lan, Jing, Sun, Keyu, Li, Boshi, Sun, Guangchao, Yang, Huawen, Shi, Yuejin, Li, Ruipeng, Song, Xirui, Liu, Mingxi, Zhu, Dalong, Yin, Huanlai, Wang, Xuan, Song, Zhaoyang, Lu, Hongchi, Jiang, Tongsen, Zheng, and Lianxin, Liu
Subjects: Feedback, Physiological, Male, Tumor Suppressor Proteins, Proteins, Middle Aged, Leukemia Inhibitory Factor, Cholangiocarcinoma, Mice, MicroRNAs, Bile Duct Neoplasms, Disease Progression, Animals, Humans, Female, Adaptor Proteins, Signal Transducing, Signal Transduction
Abstract: Increasing evidence supports a role for N-myc downstream-regulated gene 2 (NDRG2) deregulation in tumorigenesis. We investigated the roles and mechanisms of NDRG2 in human cholangiocarcinoma (CCA) progression. In the present study, expression of NDRG2, microRNA (miR)-181c and leukemia inhibitory factor (LIF) in human CCA and adjacent nontumor tissues were examined. The effects of NDRG2 on CCA tumor growth and metastasis were determined both in vivo and in vitro. The role of the NDRG2/LIF/miR-181c signaling pathway in cholangiocarcinogenesis and metastasis were investigated both in vivo and in vitro. The results showed that human CCA tissues exhibited decreased levels of NDRG2 and increased levels of miR-181c and LIF compared with nontumor tissues. NDRG2 could inhibit CCA cell proliferation, chemoresistance, and metastasis both in vitro and in vivo. We found that NDRG2 is a target gene of miR-181c, and the down-regulation of NDRG2 was attributed to miR-181c overexpression in CCA. Furthermore, miR-181c can be activated by LIF treatment, whereas NDRG2 could inhibit LIF transcription through disrupting the binding between Smad, small mothers against decapentaplegic complex and LIF promoter. Down-regulation of NDRG2 and overexpression of miR-181c or LIF are significantly associated with a poorer overall survival (OS) in CCA patients. Finally, we found that a combination of NDRG2, miR-181c, and LIF expression is a strong predictor of prognosis in CCA patients.These results establish the counteraction between NDRG2 and LIF/miR-181c as a key mechanism that regulates cholangiocarcinogenesis and metastasis. Our results elucidated a novel pathway in NDRG2-mediated inhibition of cholangiocarcinogenesis and metastasis and suggest new therapeutic targets, including NDRG2, LIF, miR-181c, and transforming growth factor beta, in CCA prevention and treatment. (Hepatology 2016;64:1606-1622).
Published: 2016

95. [Impact of octreotide on pancreatic fistula after pancreaticoduodenectomy: a prospective study]

Author: Rui, Kong, Jisheng, Hu, Le, Li, Gang, Wang, Hua, Chen, Xuewei, Bai, Yongwei, Wang, Linfeng, Wu, Hongchi, Jiang, and Bei, Sun
Subjects: Pancreatic Fistula, Pancreatectomy, Incidence, Anastomosis, Surgical, Pancreatic Ducts, Humans, Prospective Studies, Octreotide, Perioperative Period, Pancreas, Pancreaticoduodenectomy
Abstract: To investigate the effect of utilizing octreotide during perioperative period on pancreatic fistula after pancreaticoduodenectomy (PD).Three hundreds and six patients admitted from January 2010 to October 2014, who prepared to undergo pancreaticoduodenectomy (PD) were randomly divided into octreotide group (147 cases) and control group (159 cases). In octreotide group, octreotide was used in subcutaneous injection instantly after PD, each 8 hours until postoperative 10(th) day, and patients in control group were injected with the same volume of saline. Differences of pancreatic fistula (Grade A, Grade B, Grade C), hospitalization days and treatment cost were compared. χ(2) test, t-test and Fisher exact test were used to analyzed to the data, respectively.No statistical significance (P0.05) between two groups in the incidence of pancreatic fistula after PD (Grade A: 8.8% vs. 10.2%, Grade B: 2.7% vs. 4.4%, Grade C: 0.7% vs. 1.3%; χ(2)=0.197, 0.700, 0.288; P=0.657, 0.403, 0.591), the length of hospitalization((12.1±1.2)days vs. (13.0±1.2)days)(t=1.711, P=0.104) and treatment cost (79 700±6 700 vs. 77 600±5 200)(t=1.378, P=0.185). When accompanied with high risk factors, such as soft texture of pancreas, pancreatic duct size less than 3 mm, BMI≥25 kg/m(2) and diabetes, compared with control group, octreotide group had the lower incidence rate of pancreatic fistula and clinical correlative pancreatic fistula(all P0.05) after PD.Generally, octreotide makes no contribution to reduce the incidence of pancreatic fistula after PD. However, for patients who is accompanied with high risk factors, such as soft texture of pancreas, pancreatic duct size less than 3 mm, BMI≥25 kg/m(2) and diabetes, octreotide can effectively prevent pancreatic fistula after PD.
Published: 2016

96. Development of splenic surgery in China

Author: Hongchi Jiang, Yue Gao, and Xian-qi Zhao
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Spleen transplantation, Splenectomy, General Medicine, Organ transplantation, Surgery, Clinical Practice, Medicine public health, medicine, Laparoscopy, business, China
Abstract: Splenic surgery has enjoyed rapid progress for the past decades in China. Based on continuously solidifying theories and clinical practice, many advanced concepts with applicable clinical frameworks have been established, thus making splenic surgery an indispensable division in modern surgery. In this study, the authors try to give an overview of the developments in this field. Spleen function is a key issue that generally guides advances in splenic surgery. The old knowledge of the "dispensable spleen" has been abandoned, while the exact role that it plays in the body continues to be unveiled. Now, standard grading for splenic injury and the respective guidelines for clinical management have been established, with the use of selective instead of indiscriminate splenectomy being accepted by most experts. Various spleen sparing operations have been developed, while many advanced techniques such as laparoscopy have been introduced to splenic surgery. Spleen transplantation has greatly advanced in China, even though there are still many unsolved mysteries in this field. Altogether, splenic surgery is a new and prosperous discipline, and it is a tremendous stage for young surgeons to be part of.
Published: 2007
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97. Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Author: Xueying Sun, Hongchi Jiang, Hongtao Tan, Shangha Pan, Qing-hui Meng, Bei Sun, and Ruian Xu
Subjects: Male, Cancer Research, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Time Factors, Angiogenesis, Genetic enhancement, Blotting, Western, Genetic Vectors, Gene Expression, medicine.disease_cause, Neovascularization, Mice, Liver Neoplasms, Experimental, Cell Line, Tumor, Animals, Medicine, Chemoembolization, Therapeutic, Rats, Wistar, Angiostatins, Adeno-associated virus, Angiostatin, Neovascularization, Pathologic, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Arterial Embolization, Genetic Therapy, Dependovirus, medicine.disease, Combined Modality Therapy, Survival Analysis, Rats, Treatment Outcome, Liver, Oncology, Hepatocellular carcinoma, Cancer research, medicine.symptom, business, Liver cancer
Abstract: Transcatheter arterial embolization (TAE) is a well-established technique for unresectable hepatic malignancies. However, TAE can temporally halt the growth of hepatic tumors by blocking their arterial supply, but often tumors rapidly develop collateral blood vessels via angiogenesis. We have previously demonstrated that intraportal delivery of adeno-associated viral particles expressing angiostatin leads to long-term expression of angiostatin capable of inhibiting angiogenesis and suppressing the outgrowth of tumors in the liver. Thus, we hypothesize that adeno-associated virus (AAV)-mediated antiangiogenic therapy could enhance the efficacy of TAE to combat liver cancers. To achieve this objective, we engineered a recombinant AAV vector encoding rat angiostatin. Intraportal delivery of this vector led to long term and stable transgenic expression of angiostatin locally in rat hepatocytes and suppressed the growth of CBRH7919 hepatocellular carcinomas established in rat livers by inhibiting formation of neovessels. Although TAE therapy led to necrosis of liver tumors and suppressed their growth, the neovessels of tumors were rapidly reformed 3 weeks after TAE. However, intraportal injection of AAV-angiostatin inhibited the angiogenesis stimulated by TAE, synergized with TAE in suppressing growth of tumors established in livers and prolonged the survival of rats. In conclusion, these encouraging results warrant future investigation of the use of antiangiogenic therapy for enhancing the therapeutic efficacy of TAE to treat unresectable liver cancers.
Published: 2007
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98. Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats

Author: Haiquan Qiao, Xueying Sun, Hongchi Jiang, Liquan Tong, Wei Li, and Fanqiang Meng
Subjects: Male, Pathology, medicine.medical_specialty, Multiple Organ Failure, medicine.medical_treatment, Splenectomy, Apoptosis, Kidney, Proinflammatory cytokine, medicine, Animals, Aspartate Aminotransferases, Rats, Wistar, Peroxidase, Liver injury, TUNEL assay, Lung, biology, Caspase 3, Tumor Necrosis Factor-alpha, business.industry, Alanine Transaminase, medicine.disease, Rats, Intestines, medicine.anatomical_structure, Liver, Reperfusion Injury, Myeloperoxidase, biology.protein, Surgery, Tumor necrosis factor alpha, business
Abstract: Background Liver ischemia/reperfusion (I/R) results in the release of destructive proinflammatory cytokines and oxygen-derived radicals, which in turn cause injury to liver and other organs such as kidney, lung, and intestine. Splenectomy protects organs from intestinal I/R injury. Therefore, the present study aims to investigate whether splenectomy could also ameliorate multiple organ damage caused by liver I/R. Methods Wistar rats randomly assigned into 4 groups underwent sham-operation, splenectomy, hepatic I/R induced by occlusion of hepatic artery and portal vein, and splenectomy plus hepatic I/R, respectively. Blood samples were collected for assessing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, and tumor necrosis factor-α (TNF-α) levels. The activity of myeloperoxidase (MPO) in liver tissues was assessed. Livers, kidneys, lungs, and small intestines underwent histopathologic examination for scoring injury severity and TUNEL assay for cell apoptosis. The expression of caspase-3 was evaluated with Western blot analysis. Results Liver I/R resulted in liver injury as evidenced by morphologic abnormalities, increased serum activities of AST and ALT, and increased percentage of apoptotic cells. The activity of MPO in liver tissues and the serum levels of TNF-α were increased after I/R. Splenectomy significantly decreased the histologic severity score, apoptotic index, MPO activity, and serum levels of AST, ALT, and TNF-α. Hepatic I/R also caused damage to kidneys, lungs, and small intestines, as evaluated by histologic alterations and increased apoptotic cells; these changes were ameliorated by splenectomy. The expression of caspase-3 was upregulated in the 4 organs by hepatic I/R and inhibited by splenectomy. Conclusions Splenectomy protects the liver as well as the kidney, lung, and intestine from injury by hepatic I/R. Although the mechanism needs further investigation, this study demonstrated that splenectomy inhibited leukocyte infiltration in livers, release of TNF-α, cell apoptosis, and expression of caspase-3.
Published: 2007
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99. [The clinical analysis of autoimmune pancreatitis: a report of 21 cases]

Author: Gang, Wang, Yixuan, Ding, Bei, Sun, Hongchi, Jiang, Hua, Chen, Xuewei, Bai, Tao, Bai, Panquan, Li, and Jie, Liu
Subjects: Adult, Diagnostic Imaging, Male, CA-19-9 Antigen, Biopsy, Middle Aged, Autoimmune Diseases, Carcinoembryonic Antigen, Pancreatectomy, Pancreatitis, Immunoglobulin G, Humans, Female, Steroids, Pancreas, Retrospective Studies
Abstract: To investigate the clinical feature, diagnostic and therapeutic experience of autoimmune pancreatitis (AIP).Twenty-one patients with AIP treated in the First Affiliated Hospital, Harbin Medical University from January 2006 to July 2014 were analyzed retrospectively. There were 15 men and 6 women among the 21 cases and the age ranged from 36 to 64 years. The characters of diagnosis and treatment of AIP were explored through clinical symptoms, imaging features, serologic test results, diagnostic treatment, and histopathologic characteristics.All the patients showed obstructive jaundice and upper abdominal pain to different extents as major manifestations and the levels of serum IgG4, CA19-9, CEA were elevated in 16 cases (76.2%), 6 cases (28.5%) and 3 cases (14.2%), respectively. CT showed diffuse enlargement of the pancreas in 9 cases, localized pancreatic head enlargement in 3 cases and focally pancreatic mass in 9 cases. AIP was confirmed by extrapancreatic involvement, radiological and serological results plus biopsy in 11 cases (52.4%), interpretation of response to steroid in 3 cases (14.3%) and open laparotomy in 7 cases (33.3%). Surgery included choledochojejunostomy in 3 cases, cholecystojejunostomy in 1 case, pancreaticoduodenectomy in 2 cases and distal pancreatectomy combined with splenectomy in 1 case. The pathologic results displayed massive lymphocytes and plasma cells infiltration in the pancreatic tissues as well as parenchymal fibrosis. Except for 1 patient who had no symptom, the regular steroid therapy was performed (oral prednisone) and all the patients were cured. The follow-up time range was from 3 to 93 months, 4 cases (19.0%) were recurrent followed by the symptoms alleviated after the steroid was applied again.AIP is rare and characterized by non-specific clinical manifestations so that the early diagnosis is difficult with a high misdiagnosis rate. The clinicians should strengthen the recognition of AIP and the definite diagnosis depends on the combination of clinical manifestations, radiological, serological and histopathological results so as to avoid the unnecessary operation.
Published: 2015

100. A preliminary study of ALPPS procedure in a rat model

Author: Yingjian Liang, Jiabei Wang, Boshi Sun, Shangha Pan, Hongchi Jiang, Huanlai Wang, Lulu Li, Guangchao Yang, Lianxin Liu, Jing Sun, Huawen Shi, Tongsen Zheng, Dalong Yin, Changming Xie, and Wan Yee Lau
Subjects: Male, STAT3 Transcription Factor, medicine.medical_specialty, medicine.medical_treatment, Rat model, Urology, Portal vein ligation, Article, Remnant liver, Rats, Sprague-Dawley, medicine, Animals, Hepatectomy, Aspartate Aminotransferases, Ligation, Multidisciplinary, biology, business.industry, Portal Vein, NF-kappa B, Proteins, Alanine Transaminase, YAP-Signaling Proteins, Liver regeneration, Surgery, Liver Regeneration, Alanine transaminase, Liver, biology.protein, Animal studies, Atrophy, business, Apoptosis Regulatory Proteins
Abstract: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been reported to be a novel surgical technique that provides fast and effective growth of liver remnant. Despite occasional reports on animal studies, the mechanisms of rapid liver regeneration in ALPPS remains unclear. In the present study, we intend to develop a reproducible rat model to mimick ALPPS and to explore the underlying mechanisms. Rats assigned to the portal vein ligation (PVL), left lateral lobe (LLL) resection, transection and sham groups served as controls. Results indicated that the regeneration rate in the remnant liver after ALPPS was two times relative to PVL, whereas rats with transection alone showed minimal volume increase. The expression levels of Ki-67 and PCNA were about ten-fold higher after ALPPS compared with the transection and LLL resection groups and four-fold higher compared with the PVL group. The levels of TNF-α, IL-6 and HGF in the regenerating liver remnant were about three-fold higher after ALPPS than the controls. There was a more significant activation of NF-κB p65, STAT3 and Yap after ALPPS, suggesting synergistic activation of the pathways by PVL and transection, which might play an important role in liver regeneration after ALPPS.
Published: 2015
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