65 results on '"Caiyun Fu"'
Search Results
2. Therapeutic potential for targeting Annexin A1 in fibrotic diseases
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Zhibin Yan, Xurui Cheng, Tao Wang, Xiangyu Hong, Gang Shao, and Caiyun Fu
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Annexin A1 ,Anti-inflammatory ,Fibrosis ,Fibrotic diseases ,Sequence alignment ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Annexin A1, a well-known endogenous anti-inflammatory mediator, plays a critical role in a variety of pathological processes. Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases. Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis. However, the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive, and even the functions of Annexin A1 in fibrotic diseases are still paradoxical. This review focuses on the roles of Annexin A1 in the development of fibrosis of lung, liver, heart, and other tissues, with emphasis on the therapy potential of Annexin A1 in fibrosis, and presents future research interests and directions in fibrotic diseases.
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- 2022
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3. Therapeutic peptides: current applications and future directions
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Lei Wang, Nanxi Wang, Wenping Zhang, Xurui Cheng, Zhibin Yan, Gang Shao, Xi Wang, Rui Wang, and Caiyun Fu
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Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.
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- 2022
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4. Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia
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Huafeng Wang, Chang Yang, Ting Shi, Yi Zhang, Jiejing Qian, Yungui Wang, Yongxian Hu, Liping Mao, Xiujin Ye, Fang Liu, Zhenfang Xi, Lihong Shou, Caiyun Fu, Hua Naranmandura, Jie Jin, and Hong-Hu Zhu
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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5. Circadian‐rhythm‐regulating hormones: Key factors to regulate breast cancer metastasis via circulating tumor cells
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Chenguang Liu, Lingxiao Guo, and Caiyun Fu
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Medicine - Published
- 2022
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6. Age-induced changes in lung microenvironment: from melanoma dormancy to outgrowth
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Juan Jin, Li Li, and Caiyun Fu
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Medicine ,Biology (General) ,QH301-705.5 - Published
- 2023
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7. Cystathionine-β-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation
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Haoran Zhu, Keefe T Chan, Xinran Huang, Carmelo Cerra, Shaun Blake, Anna S Trigos, Dovile Anderson, Darren J Creek, David P De Souza, Xi Wang, Caiyun Fu, Metta Jana, Elaine Sanij, Richard B Pearson, and Jian Kang
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senescence ,PI3K/AKT signaling ,cystathionine-β-synthase ,gastric cancer ,oxidative stress ,glutathione ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Hyperactivation of oncogenic pathways downstream of RAS and PI3K/AKT in normal cells induces a senescence-like phenotype that acts as a tumor-suppressive mechanism that must be overcome during transformation. We previously demonstrated that AKT-induced senescence (AIS) is associated with profound transcriptional and metabolic changes. Here, we demonstrate that human fibroblasts undergoing AIS display upregulated cystathionine-β-synthase (CBS) expression and enhanced uptake of exogenous cysteine, which lead to increased hydrogen sulfide (H2S) and glutathione (GSH) production, consequently protecting senescent cells from oxidative stress-induced cell death. CBS depletion allows AIS cells to escape senescence and re-enter the cell cycle, indicating the importance of CBS activity in maintaining AIS. Mechanistically, we show this restoration of proliferation is mediated through suppressing mitochondrial respiration and reactive oxygen species (ROS) production by reducing mitochondrial localized CBS while retaining antioxidant capacity of transsulfuration pathway. These findings implicate a potential tumor-suppressive role for CBS in cells with aberrant PI3K/AKT pathway activation. Consistent with this concept, in human gastric cancer cells with activated PI3K/AKT signaling, we demonstrate that CBS expression is suppressed due to promoter hypermethylation. CBS loss cooperates with activated PI3K/AKT signaling in promoting anchorage-independent growth of gastric epithelial cells, while CBS restoration suppresses the growth of gastric tumors in vivo. Taken together, we find that CBS is a novel regulator of AIS and a potential tumor suppressor in PI3K/AKT-driven gastric cancers, providing a new exploitable metabolic vulnerability in these cancers.
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- 2022
- Full Text
- View/download PDF
8. Differences of Corneal Biomechanics Among Thin Normal Cornea, Forme-Fruste Keratoconus, and Cornea After SMILE
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Di Zhang, Lei Tian, Haixia Zhang, Yan Zheng, Caiyun Fu, Changbin Zhai, Ying Jie, and Lin Li
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thin normal cornea ,FFKC ,post-SMILE ,corneal biomechanicans ,CorVis ST ,Biotechnology ,TP248.13-248.65 - Abstract
Background: To compare the corneal biomechanics of thin normal cornea (TNC) with thinnest corneal thickness (TCT) (≤500 µm), forme-fruste keratoconus (FFKC) and cornea after small incision lenticule extraction (Post-SMILE) had their central corneal thickness (CCT) matched by Corneal Visualization Scheimpflug Technology (Corvis ST).Methods: CCT were matched in 23 eyes with FFKC, 23 eyes by SMILE in 3 months post-operatively, and 23 TNC eyes. The differences in corneal biomechanics by Corvis ST among the three groups were compared.Results: There was no significant difference in CCT among the three groups, and the biomechanically corrected intraocular pressure (bIOP) did not differ significantly among the three groups (all p > 0.05). There were significant differences in most DCR parameters between pre- and post-operatively (all p < 0.05). Compared with TNC, the values of corneal deflection amplitude during the first applanation (A1DA), length at the first applanation (A1L), corneal deflection amplitude during the second applanation (A2DA), and maximum deformation amplitude (DA) decreased in 3 months after SMILE (all p < 0.05), these values increased in the FFKC (all p < 0.05).Conclusion: The majority of the DCR parameters were different among the three groups. The parameters A1DA, A1L, A2DA, and DA may be different between TNC and Post-SMILE, TNC and FFKC, and Post-SMILE and FFKC.
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- 2022
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9. Targeting Annexin A1 as a Druggable Player to Enhance the Anti-Tumor Role of Honokiol in Colon Cancer through Autophagic Pathway
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Xi Wang, Gang Shao, Xiangyu Hong, Yue Shi, Yiting Zheng, Yucheng Yu, and Caiyun Fu
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annexin A1 ,colon cancer ,hyperproliferation ,honokiol ,autophagy ,reactive oxygen species ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Colon cancer is one of the most common digestive tract malignancies, having the second highest mortality rate among all tumors, with a five-year survival of advanced patients of only 10%. Efficient, targeted drugs are still lacking in treating colon cancer, so it is urgent to explore novel druggable targets. Here, we demonstrated that annexin A1 (ANXA1) was overexpressed in tumors of 50% of colon cancer patients, and ANXA1 overexpression was significantly negatively correlated with the poor prognosis of colon cancer. ANXA1 promoted the abnormal proliferation of colon cancer cells in vitro and in vivo by regulating the cell cycle, while the knockdown of ANXA1 almost totally inhibited the growth of colon cancer cells in vivo. Furthermore, ANXA1 antagonized the autophagic death of honokiol in colon cancer cells via stabilizing mitochondrial reactive oxygen species. Based on these results, we speculated that ANXA1 might be a druggable target to control colon cancer and overcome drug resistance.
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- 2023
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10. Editorial: Clinical Therapeutic Development Against Cancers Resistant to Targeted Therapies
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Fanfan Zhou, Hong Zhu, and Caiyun Fu
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cancer resistance ,targeted therapies ,therapeutic development ,anti-cancer therapeutics ,therapeutic resistance ,Therapeutics. Pharmacology ,RM1-950 - Published
- 2022
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11. A Novel Mechanism of Endoplasmic Reticulum Stress‐ and c‐Myc‐Degradation‐Mediated Therapeutic Benefits of Antineurokinin‐1 Receptor Drugs in Colorectal Cancer
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Yue Shi, Xi Wang, Yueming Meng, Junjie Ma, Qiyu Zhang, Gang Shao, Lingfei Wang, Xurui Cheng, Xiangyu Hong, Yong Wang, Zhibin Yan, Yihai Cao, Jian Kang, and Caiyun Fu
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chemotherapy resistance ,ER stress ,human colorectal cancer ,MAPK signal pathway ,neurokinin‐1 receptor ,Science - Abstract
Abstract The neurokinin‐1 receptor (NK‐1R) antagonists are approved as treatment for chemotherapy‐associated nausea and vomiting in cancer patients. The emerging role of the substance P‐NK‐1R system in oncogenesis raises the possibility of repurposing well‐tolerated NK‐1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK‐1R expression have poor survival, and NK‐1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK‐1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal‐regulated kinase (ERK)‐c‐Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA‐like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP‐homologous protein (CHOP). Moreover, NK‐1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5‐fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK‐c‐Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK‐1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.
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- 2021
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12. Exploring the Biomechanical Properties of the Human Cornea In Vivo Based on Corvis ST
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Di Zhang, Haixia Zhang, Lei Tian, Yan Zheng, Caiyun Fu, Changbin Zhai, and Lin Li
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cornea ,corneal biomechanical properties ,in vivo ,CorVis ST ,visco-hyperelastic model ,Biotechnology ,TP248.13-248.65 - Abstract
Purpose: The aim of this study was to provide a method to determine corneal nonlinear viscoelastic properties based on the output data of corneal visualization Scheimpflug technology (Corvis ST).Methods: The Corvis ST data from 18 eyes of 12 healthy humans were collected. Based on the air-puff pressure and the corneal displacement from the Corvis ST test of normal human eyes, the work done by the air-puff attaining the whole corneal displacement was obtained. By applying a visco-hyperelastic strain energy density function of the cornea, in which the first-order Prony relaxation function and the first-order Ogden strain energy were employed, the corneal strain energy during the Corvis ST test was calculated. Then the work done by the air-puff attaining the whole corneal displacement was completely regarded as the strain energy of the cornea. The identification of the nonlinear viscoelastic parameters was carried out by optimizing the sum of difference squares of the work and the strain energy using the genetic algorithm.Results: The visco-hyperelastic model gave a good fit to the data of corneal strain energy with time during the Corvis ST test (R2 > 0.95). The determined Ogden model parameter μ ranged from 0.42 to 0.74 MPa, and α ranged from 32.76 to 55.63. The parameters A and τ in the first-order Prony function were 0.09–0.36 and 1.21–1.95 ms, respectively.Conclusion: It is feasible to determine the corneal nonlinear viscoelastic properties based on the corneal contour information and air-puff pressure of the Corvis ST test.
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- 2021
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13. Organoid-derived C-Kit+/SSEA4− human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents
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Ting Zou, Lixiong Gao, Yuxiao Zeng, Qiyou Li, Yijian Li, Siyu Chen, Xisu Hu, Xi Chen, Caiyun Fu, Haiwei Xu, and Zheng Qin Yin
- Subjects
Science - Abstract
Stem cell transplantation to treat retinal degeneration could be limited by the degenerative microenvironment. Here, the authors show that C-Kit+/SSEA4– progenitor cells enriched from human embryonic stem cell derived retinal organoids protect retinal structure, suppress microglial activation, gliosis and inflammation.
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- 2019
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14. Apaf-1/caspase-4 pyroptosome: a mediator of mitochondrial permeability transition-triggered pyroptosis
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Gang Shao, Lingfei Wang, Xi Wang, and Caiyun Fu
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Medicine ,Biology (General) ,QH301-705.5 - Published
- 2021
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15. Aloperine inhibits RANKL-induced osteoclast differentiation via suppressing the MAPK signaling pathways
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Xiang Wu, Caiyun Fu, Xuefeng He, and Shaolei Wang
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Agronomy and Crop Science ,Food Science - Abstract
To figure out the molecular mechanism of aloperine (ALO) on receptor activator of nuclear factor (NF)-kappa-B (κb) ligand (RANKL)-caused osteoclast differentiation. The histopathological analysis and tartrate-resistant acid phosphatase (TRAP) staining assays were applied to check the extent of bone loss of the femur. Then, the protein expressions of nitric oxide synthase 2, glutathione reductase, nuclear erythroid 2-related factor 2, heme oxygenase-1, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1, and catalase were checked in RAW264.7, a macrophage cell line, by enzyme-linked-immunosorbent serologic assay and Western blot analysis. Further, the TRAP staining and quantitative polymerase chain reaction assay were applied to characterize the level of RAW264.7 osteoclast differentiation. Besides, Western blot assay was used to check the protein expressions of extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38 in RAW264.7. Finally, ERK activation blocker U0126 was used to inhibit mitogen-activated protein kinase (MAPK) signaling pathway to determine the effect of MAPK signaling pathway on RAW264.7 osteoclast differentiation. In this study, the results demonstrated that ALO could inhibit lipopolysaccharide-induced bone loss in vivo in a dose-dependent manner, with significant inhibitory effects at high doses. Further research indicated that ALO could inhibit RANKL-induced oxidative stress and osteoclast differentiation of RAW264.7. Then, ALO could inactivate MAPK signaling pathway. Finally, the results showed that inhibition of MAPK signaling pathway could increase ALO inhibition of RANKL-caused osteoclast differentiation. ALO inhibits RANKL-caused osteoclast differentiation by suppressing the MAPK signaling pathways.
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- 2023
16. Antimicrobial peptides: mechanism of action, activity and clinical potential
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Jian Kang, Qiyu Zhang, Xurui Cheng, Zhi-Bin Yan, Jun Liu, Yueming Meng, Jun-Jie Ma, Gang Shao, Caiyun Fu, and Xiang-Yu Hong
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Pore Forming Cytotoxic Proteins ,Medicine (General) ,Antimicrobial peptides ,Computational biology ,Review ,Mechanism of action ,Antimicrobial resistance ,Theta defensin ,Antibiotic resistance ,R5-920 ,medicine ,Humans ,Low toxicity ,business.industry ,Biological activity ,General Medicine ,Bacterial Infections ,Antimicrobial ,Clinical application ,Anti-Bacterial Agents ,Military Science ,medicine.symptom ,business - Abstract
The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics. Supplementary Information The online version contains supplementary material available at 10.1186/s40779-021-00343-2.
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- 2021
17. Association of a single amino acid replacement with dorsal pigmentation in a lizard from the Qinghai-Tibetan Plateau
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Haojie Tong, Gang Shao, Leijie Wang, Jiasheng Li, Tao Wang, Lun Zhang, Yudie Lv, Fei Ye, Caiyun Fu, and Yuanting Jin
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Structural Biology ,General Medicine ,Molecular Biology ,Biochemistry - Published
- 2023
18. Cystathionine-β-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation
- Author
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Keefe T Chan, Haoran Zhu, Xinran Huang, Carmelo Cerra, Shaun Blake, Anna S Trigos, Dovile Anderson, Darren J Creek, David P De Souza, Xi Wang, Caiyun Fu, Metta Jana, Elaine Sanij, Richard B Pearson, and Jian Kang
- Subjects
Phosphatidylinositol 3-Kinases ,Cystathionine ,Glycogen Synthase ,General Immunology and Microbiology ,Stomach Neoplasms ,General Neuroscience ,Cystathionine beta-Synthase ,Humans ,Hydrogen Sulfide ,General Medicine ,Glutathione ,Proto-Oncogene Proteins c-akt ,General Biochemistry, Genetics and Molecular Biology - Abstract
Hyperactivation of oncogenic pathways downstream of RAS and PI3K/AKT in normal cells induces a senescence-like phenotype that acts as a tumor-suppressive mechanism that must be overcome during transformation. We previously demonstrated that AKT-induced senescence (AIS) is associated with profound transcriptional and metabolic changes. Here, we demonstrate that human fibroblasts undergoing AIS display upregulated cystathionine-β-synthase (CBS) expression and enhanced uptake of exogenous cysteine, which lead to increased hydrogen sulfide (H2S) and glutathione (GSH) production, consequently protecting senescent cells from oxidative stress-induced cell death. CBS depletion allows AIS cells to escape senescence and re-enter the cell cycle, indicating the importance of CBS activity in maintaining AIS. Mechanistically, we show this restoration of proliferation is mediated through suppressing mitochondrial respiration and reactive oxygen species (ROS) production by reducing mitochondrial localized CBS while retaining antioxidant capacity of transsulfuration pathway. These findings implicate a potential tumor-suppressive role for CBS in cells with aberrant PI3K/AKT pathway activation. Consistent with this concept, in human gastric cancer cells with activated PI3K/AKT signaling, we demonstrate that CBS expression is suppressed due to promoter hypermethylation. CBS loss cooperates with activated PI3K/AKT signaling in promoting anchorage-independent growth of gastric epithelial cells, while CBS restoration suppresses the growth of gastric tumors in vivo. Taken together, we find that CBS is a novel regulator of AIS and a potential tumor suppressor in PI3K/AKT-driven gastric cancers, providing a new exploitable metabolic vulnerability in these cancers.
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- 2022
19. Author response: Cystathionine-β-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation
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Keefe T Chan, Haoran Zhu, Xinran Huang, Carmelo Cerra, Shaun Blake, Anna S Trigos, Dovile Anderson, Darren J Creek, David P De Souza, Xi Wang, Caiyun Fu, Metta Jana, Elaine Sanij, Richard B Pearson, and Jian Kang
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- 2022
20. Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia
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Hong-Hu Zhu, Yungui Wang, Fang Liu, Caiyun Fu, Ting Shi, Liping Mao, Chang Yang, Zhenfang Xi, Lihong Shou, Yongxian Hu, Xiujin Ye, Hua Naranmandura, Jie Jin, Huafeng Wang, Jiejing Qian, and Yi Zhang
- Subjects
Adult ,Male ,Immunology ,Biochemistry ,Young Adult ,chemistry.chemical_compound ,Clinical trials ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Correspondence ,Humans ,Medicine ,Philadelphia Chromosome ,RC254-282 ,Aged ,Retrospective Studies ,Sulfonamides ,Acute lymphocytic leukaemia ,Venetoclax ,business.industry ,Ponatinib ,Imidazoles ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell Biology ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Bridged Bicyclo Compounds, Heterocyclic ,Ph+ acute lymphoblastic leukemia ,Pyridazines ,chemistry ,Oncology ,Mutation ,Cancer research ,Female ,business - Abstract
The outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) have greatly improved in tyrosine kinase inhibitors (TKIs) era and is just moving to a chemo-free era using dasatinib and blinatumomab (Foà R, N Engl J Med. 2020; Ravandi F, Blood. 2019). However, the outcome of T315I/compound-mutated Ph+ ALL patients is dismal (Cortes JE, N Engl J Med. 2013), representing an unmet need. Recently, Scherr et al reported the curative potential of venetoclax-TKIs-dexamethasone in a BCR-ABL+ mouse model (Scherr M, Leukemia. 2019). Here, we firstly reported outcome of 19 T315I/compound-mutated relapsed/refractory (R/R)Ph+ ALL patients treated with venetoclax(100mg d1, 200mg d2, 400mg d3-28), ponatinib (45mg d1-28) and dexamethasone (0.15mg/kg d1-21,0.075mg/kg d22-28)(VPD regimen) (Figure 1A) between January 2020 and May 2021. They had already received a median of 3 lines of salvage therapy. After one cycle, 17 patients (89.5%) achieved CR/CRi [13 minimal residual disease (MRD)--negative by flow cytometry;11 major molecular remission (MMR);8 complete molecular remission (CMR)] (Figure 1B). Subsequently relapse occurred in 1/6 [allogeneic hematopoietic cell transplantation (allo-HSCT) group)] and 7/11 (VDP consolidation group). At a median follow-up of 259 days, the median EFS and OS of patients from the starting VPD treatment was 242 and 400 days. Adverse events of VPD regimen were listed in Figure 1C. Grade 3-4 neutropenia, anemia and thrombocytopenia occurred in 73.7%,36.8% and 52.6% patients. 5.3% and 16% patients have grade 3-4 rash and infection separately. No tumor lysis syndrome or death occurred. 7/19 patients were treated safety outpatient. Moreover, venetoclax had a strong synergistic effect with ponatinib and dexamethasone on inducing apoptosis of primary blast cells and BaF3 cells expressing p190 BCR/ABL with T315I-mutation in vitro, with a combination index of 0.019 when the suppressing rate is 0.05, while the effect was significant decreased when ponatinib was replaced by dasatinib (Figure 1D-F), a prominent change of mitochondrial membrane potential as well as the cleavage of PARP were also observed in triple-combination treatment group (Figure 1G-H). For T315I/compound-mutated Ph+ ALL, VPD regimen exhibited 89.5% CR/CRi rate, with deep molecular remission (57.9% MMR), while ponatinib alone showed 41% hematologic response (Cortes JE, N Engl J Med. 2013), which supported by the preclinical data suggesting TKIs and venetoclax are highly synergistic in BCR-ABL + cells in vitro (Scherr M, Leukemia. 2019). 7/11 and 1/6 patients subsequently relapsed in continuous VPD and allo-HSCT postremission treatment group separately, suggested bridging to allo-HSCT after remission is warranted. Moreover, novel compounds such as blinatumomab showed a preliminary efficacy (Couturier MA, Leuk Lymphoma. 2021). In summary, VPD regimen provides a novel treatment for T315I/compound-mutated R/R Ph+ALL under a complete oral and chemo-free model. A clinical trial also using similar VPD regimen for treatment of R/R Ph+ ALL is ongoing now (Short NJ, Am J Hematol. 2021). Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
- Published
- 2022
21. Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo
- Author
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Lingfei Wang, Hongzhang Wu, Xi Wang, Gang Shao, Yueming Meng, Xiaoyuan Jia, Tao Wang, Caiyun Fu, Xurui Cheng, Feiyan Huang, and Tianxin Yang
- Subjects
0301 basic medicine ,Pharmacology ,Chemotherapy ,Myeloid ,business.industry ,Necroptosis ,medicine.medical_treatment ,Pharmaceutical Science ,Myeloid leukemia ,Combination chemotherapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,In vivo ,030220 oncology & carcinogenesis ,Drug Discovery ,Toxicity ,medicine ,Cancer research ,business ,Aprepitant ,medicine.drug - Abstract
Purpose Acute myeloid leukemia (AML) is a complex malignancy characterized by the clonal expansion of immature myeloid precursors. The standard treatment for newly diagnosed AML is chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines with disappointing clinical outcomes and severe adverse effects, such as symptomatic bradycardia, neurotoxicity. Thus, it is promising to treat AML through combination drug therapy to reduce the adverse effects of chemotherapeutics. In our recent published PNAS paper, we reported that NK-1R antagonists, both Aprepitant and SR140333, induce apoptosis of myeloid leukemia cells by inducing oxidative stress through mitochondrial calcium overload. We, therefore, tested the hypothesis of the combination Ara-C with NK-1R antagonist could enhance the efficacy of Ara-C. Methods MTT assay was employed to detect the cell proliferation. Flow cytometry was applied to detect the cell cycle and necrosis. PI uptake and LDH release assay were used to detect the disintegration of the plasma membrane. Xenograft model was constructed to explore the effect of combination Ara-C with Aprepitant in vivo. Results Our results showed that Aprepitant sensitizes HL60 cells to the cytotoxic effects of Ara-C more than 5-fold by enhancing G0/G1 cell cycle arrest and necrosis in vitro. Furthermore, Nec-1, a specific inhibitor of necroptosis, could recover the cell proliferative viability significantly. Attractively, once every 2-days regimen of Ara-C (5 mg/kg) and Aprepitant (10 mg/kg) via in situ injection dramatically reduced the tumor volume from 2175.0 ± 341.9 mm3 in the vehicle group to 828.4 ± 232.4 mm3 in the combination group without obvious toxicity in human myeloid leukemia xenograft mice. Conclusion Taken together, reduced dose of Ara-C combination with moderate Aprepitant provides more effective therapeutical methods for AML treatment in vitro and in vivo with the elimination of the toxicity of Ara-C, which may pay new avenue for the usage of the routine chemotherapy drug Ara-C with low dose to enhance efficacy and reduce toxicity in clinical practice.
- Published
- 2020
22. Editorial: Clinical Therapeutic Development Against Cancers Resistant to Targeted Therapies
- Author
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Fanfan, Zhou, Hong, Zhu, and Caiyun, Fu
- Subjects
Pharmacology ,therapeutic resistance ,Editorial ,anti-cancer therapeutics ,therapeutic development ,cancer resistance ,targeted therapies - Published
- 2021
23. A Novel Mechanism of Endoplasmic Reticulum Stress‐ and c‐Myc‐Degradation‐Mediated Therapeutic Benefits of Antineurokinin‐1 Receptor Drugs in Colorectal Cancer
- Author
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Xurui Cheng, Jun-Jie Ma, Yueming Meng, Yong Wang, Yue Shi, Zhi-Bin Yan, Jian Kang, Caiyun Fu, Xiang-Yu Hong, Xi Wang, Gang Shao, Lingfei Wang, Yihai Cao, and Qiyu Zhang
- Subjects
MAPK/ERK pathway ,chemotherapy resistance ,Quinuclidines ,Science ,General Chemical Engineering ,Transplantation, Heterologous ,General Physics and Astronomy ,Medicine (miscellaneous) ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,CHOP ,MAPK signal pathway ,medicine.disease_cause ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Proto-Oncogene Proteins c-myc ,Mice ,Neurokinin-1 Receptor Antagonists ,Piperidines ,Cell Line, Tumor ,human colorectal cancer ,medicine ,Animals ,Humans ,General Materials Science ,Protein kinase A ,Extracellular Signal-Regulated MAP Kinases ,Research Articles ,neurokinin‐1 receptor ,Kinase ,Endoplasmic reticulum ,General Engineering ,Cancer ,medicine.disease ,Endoplasmic Reticulum Stress ,Survival Rate ,Drug Resistance, Neoplasm ,Cancer research ,Unfolded protein response ,Carcinogenesis ,ER stress ,Colorectal Neoplasms ,Aprepitant ,Research Article ,Signal Transduction - Abstract
The neurokinin‐1 receptor (NK‐1R) antagonists are approved as treatment for chemotherapy‐associated nausea and vomiting in cancer patients. The emerging role of the substance P‐NK‐1R system in oncogenesis raises the possibility of repurposing well‐tolerated NK‐1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK‐1R expression have poor survival, and NK‐1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK‐1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal‐regulated kinase (ERK)‐c‐Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA‐like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP‐homologous protein (CHOP). Moreover, NK‐1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5‐fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK‐c‐Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK‐1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment., The neurokinin‐1 receptor antagonists are repurposed as a new treatment option for patients with colorectal cancer via activation of endoplasmic reticulum stress to induce apoptosis.
- Published
- 2021
24. The antimicrobial peptide PFR induces necroptosis mediated by ER stress and elevated cytoplasmic calcium and mitochondrial ROS levels: cooperation with Ara-C to act against acute myeloid leukemia
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Feiyan Huang, Qiyu Zhang, Yueming Meng, Caiyun Fu, Yuanting Jin, Lingfei Wang, Tianxin Yang, Xi Wang, Gang Shao, and Yudie Lv
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chemistry.chemical_classification ,Mitochondrial ROS ,Haematological cancer ,Cancer Research ,Letter ,Cytoplasmic calcium ,Necroptosis ,lcsh:R ,Myeloid leukemia ,lcsh:Medicine ,Drug development ,Peptide ,Antimicrobial ,chemistry ,lcsh:Biology (General) ,Genetics ,Unfolded protein response ,Cancer research ,lcsh:QH301-705.5 - Published
- 2019
25. Advancements of Annexin A1 in inflammation and tumorigenesis
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Caiyun Fu, Hanwei Zhou, Yuanting Jin, Qiyu Zhang, and Gang Shao
- Subjects
0301 basic medicine ,Cancer ,Inflammation ,Biology ,medicine.disease_cause ,medicine.disease ,Review article ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Phospholipid Binding ,Pharmacology (medical) ,medicine.symptom ,Carcinogenesis ,Annexin A1 - Abstract
Annexin A1 is a Ca2+-dependent phospholipid binding protein involved in a variety of pathophysiological processes. Accumulated evidence has indicated that Annexin A1 has important functions in cell proliferation, apoptosis, differentiation, metastasis, and inflammatory response. Moreover, the abnormal expression of Annexin A1 is closely related to the occurrence and development of tumors. In this review article, we focus on the structure and function of Annexin A1 protein, especially the recent evidence of Annexin A1 in the pathophysiological role of inflammatory and cancer. This summary will be very important for further investigation of the pathophysiological role of Annexin A1 and for the development of novel therapeutics of inflammatory and cancer based on targeting Annexin A1 protein.
- Published
- 2019
26. Apaf-1/caspase-4 pyroptosome: a mediator of mitochondrial permeability transition-triggered pyroptosis
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Caiyun Fu, Xi Wang, Gang Shao, and Lingfei Wang
- Subjects
Cancer Research ,Pyroptosome ,biology ,Inflammasomes ,Chemistry ,lcsh:R ,Pyroptosis ,lcsh:Medicine ,Caspase 4 ,Mitochondrial Transmembrane Permeability-Driven Necrosis ,Cell biology ,Mediator ,lcsh:Biology (General) ,Mitochondrial permeability transition pore ,Caspases ,Genetics ,biology.protein ,lcsh:QH301-705.5 - Published
- 2021
27. Dorsal Pigmentation and Its Association with Functional Variation in MC1R in a Lizard from Different Elevations on the Qinghai-Tibetan Plateau
- Author
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Caiyun Fu, Jiasheng Li, Gang Shao, Richard P. C. Brown, Haojie Tong, Yuanting Jin, Yudie Lv, and Yubin Wo
- Subjects
0106 biological sciences ,Male ,AcademicSubjects/SCI01140 ,Population ,Zoology ,selection ,Melanocyte ,Tibet ,010603 evolutionary biology ,01 natural sciences ,Polymorphism, Single Nucleotide ,Intraspecific competition ,03 medical and health sciences ,biology.animal ,Genetics ,medicine ,Animals ,Allele ,education ,Gene ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,biology ,Human evolutionary genetics ,Lizard ,Pigmentation ,Melanism ,Altitude ,AcademicSubjects/SCI01130 ,Lizards ,color ,reptile ,medicine.anatomical_structure ,Qinghai–Tibetan Plateau ,Female ,Receptor, Melanocortin, Type 1 ,Signal Transduction ,Research Article - Abstract
Identification of the role of the MC1R gene has provided major insights into variation in skin pigmentation in several organisms, including humans, but the evolutionary genetics of this variation is less well established. Variation in this gene and its relationship with degree of melanism was analyzed in one of the world’s highest-elevation lizards, Phrynocephalus theobaldi from the Qinghai–Tibetan Plateau. Individuals from the low-elevation group were shown to have darker dorsal pigmentation than individuals from a high-elevation group. The existence of climatic variation across these elevations was quantified, with lower elevations exhibiting higher air pressure, temperatures, and humidity, but less wind and insolation. Analysis of the MC1R gene in 214 individuals revealed amino acid differences at five sites between intraspecific sister lineages from different elevations, with two sites showing distinct fixed residues at low elevations. Three of the four single-nucleotide polymorphisms that underpinned these amino acid differences were highly significant outliers, relative to the generalized MC1R population structuring, suggestive of selection. Transfection of cells with an MC1R allele from a lighter high-elevation population caused a 43% reduction in agonist-induced cyclic AMP accumulation, and hence lowered melanin synthesis, relative to transfection with an allele from a darker low-elevation population. The high-elevation allele led to less efficient integration of the MC1R protein into melanocyte membranes. Our study identifies variation in the degree of melanism that can be explained by four or fewer MC1R substitutions. We establish a functional link between these substitutions and melanin synthesis and demonstrate elevation-associated shifts in their frequencies.
- Published
- 2020
28. Privileged Scaffolds in Drug Discovery
- Author
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Bin Yu, Ning Li, Caiyun Fu, Bin Yu, Ning Li, and Caiyun Fu
- Abstract
Privileged Scaffolds in Drug Discovery is the most complete and up-to-date work in the area. Covering a wide range of privileged structures, it is a perfect reference for scientists involved in targeted drug development. The editors recruited epserts from several prestigious Chinese institutions to cover the areas of antiviral drugs, chalcone, pyrimidine, (benz)imidazoles, natural product-derived privileged scaffolds, N-Sulfonyl carboxamides, kinase inhibitors, antitumor molecules, antineurodegenerative drugs, triazoles, oxazolidinone, indole and indoline scaffolds, tigliane diterpenoids, peptide and peptide-based drugs, quassinoids, and others including pseudonatural products, macrocycles, stable peptides and peptidomimetics. The book also explores scaffolds in drug molecules approved in recent years. Privileged Scaffolds in Drug Discovery is a complete reference for researchers in drug discovery and organic synthesis, in academic and corporate settings, who are investigating privileged structures upon which to base new drugs. Researchers in medicinal chemistry and chemical biology will also find the contents of this book valuable.Provides wide coverage of privileged scaffolds in new drug discoveryIncludes complex and diverse natural product scaffoldsCovers applications to peptides and peptide-based drugs
- Published
- 2023
29. Gasdermin: a novel therapeutic target for tumour treatment by activating anti-tumour immunity
- Author
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Caiyun Fu
- Subjects
Cancer Research ,lcsh:Biology (General) ,business.industry ,Anti tumour immunity ,lcsh:R ,Genetics ,Cancer research ,lcsh:Medicine ,Medicine ,business ,lcsh:QH301-705.5 - Published
- 2020
30. Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo
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Hongzhang, Wu, Xurui, Cheng, Feiyan, Huang, Gang, Shao, Yueming, Meng, Lingfei, Wang, Tao, Wang, Xiaoyuan, Jia, Tianxin, Yang, Xi, Wang, and Caiyun, Fu
- Subjects
neurokinin receptor antagonist ,Cell Survival ,Cytarabine ,Antineoplastic Agents ,HL-60 Cells ,Cell Cycle Checkpoints ,Neoplasms, Experimental ,acute myeloid leukemia ,combined chemotherapy ,cytosine arabinoside ,Leukemia, Myeloid, Acute ,Mice ,Animals ,Humans ,Drug Screening Assays, Antitumor ,Aprepitant ,Cell Proliferation ,Original Research - Abstract
Purpose Acute myeloid leukemia (AML) is a complex malignancy characterized by the clonal expansion of immature myeloid precursors. The standard treatment for newly diagnosed AML is chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines with disappointing clinical outcomes and severe adverse effects, such as symptomatic bradycardia, neurotoxicity. Thus, it is promising to treat AML through combination drug therapy to reduce the adverse effects of chemotherapeutics. In our recent published PNAS paper, we reported that NK-1R antagonists, both Aprepitant and SR140333, induce apoptosis of myeloid leukemia cells by inducing oxidative stress through mitochondrial calcium overload. We, therefore, tested the hypothesis of the combination Ara-C with NK-1R antagonist could enhance the efficacy of Ara-C. Methods MTT assay was employed to detect the cell proliferation. Flow cytometry was applied to detect the cell cycle and necrosis. PI uptake and LDH release assay were used to detect the disintegration of the plasma membrane. Xenograft model was constructed to explore the effect of combination Ara-C with Aprepitant in vivo. Results Our results showed that Aprepitant sensitizes HL60 cells to the cytotoxic effects of Ara-C more than 5-fold by enhancing G0/G1 cell cycle arrest and necrosis in vitro. Furthermore, Nec-1, a specific inhibitor of necroptosis, could recover the cell proliferative viability significantly. Attractively, once every 2-days regimen of Ara-C (5 mg/kg) and Aprepitant (10 mg/kg) via in situ injection dramatically reduced the tumor volume from 2175.0 ± 341.9 mm3 in the vehicle group to 828.4 ± 232.4 mm3 in the combination group without obvious toxicity in human myeloid leukemia xenograft mice. Conclusion Taken together, reduced dose of Ara-C combination with moderate Aprepitant provides more effective therapeutical methods for AML treatment in vitro and in vivo with the elimination of the toxicity of Ara-C, which may pay new avenue for the usage of the routine chemotherapy drug Ara-C with low dose to enhance efficacy and reduce toxicity in clinical practice.
- Published
- 2020
31. Genetically Encoding Quinoline Reverses Chromophore Charge and Enables Fluorescent Protein Brightening in Acidic Vesicles
- Author
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Christian Hoppmann, Caiyun Fu, Roshanak Irannejad, Tomonori Kobayashi, Bing Yang, Lei Wang, and Nanxi Wang
- Subjects
Models, Molecular ,0301 basic medicine ,1.1 Normal biological development and functioning ,Protonation ,Endocytosis ,Biochemistry ,Article ,Fluorescence ,Catalysis ,Green fluorescent protein ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,Colloid and Surface Chemistry ,Models ,Underpinning research ,Humans ,Amino Acids ,Organelles ,chemistry.chemical_classification ,Drug Carriers ,Molecular Structure ,Vesicle ,Quinoline ,Neurosciences ,Molecular ,General Chemistry ,Hydrogen-Ion Concentration ,Chromophore ,Amino acid ,Luminescent Proteins ,030104 developmental biology ,chemistry ,Genetic Code ,Hela Cells ,Chemical Sciences ,Quinolines ,Biophysics ,HeLa Cells ,Biotechnology - Abstract
Acidic vesicles and organelles play fundamental roles in a broad range of cellular events such as endocytosis, lysosomal degradation, synaptic transmission, pathogen fate, and drug delivery. Fluorescent reporters will be invaluable for studying these complex and multifunctional systems with spatiotemporal resolution, yet common fluorescent proteins are generally nonfluorescent at acidic conditions due to the decrease of anionic chromophores upon protonation, but are fluorescent at physiological pH, creating interfering fluorescence from nonvesicle regions. Here we developed a novel acid-brightening fluorescent protein (abFP) that fluoresces strongly at acidic pH but is nonfluorescent at or above neutral pH, boasting a pH profile opposite to that of common fluorescent proteins. Through expansion of the genetic code, we incorporated a quinoline-containing amino acid Qui into the chromophore of EGFP to reverse the chromophore charge. Protonation of Qui rendered a cationic chromophore, which resulted in unique fluorescence increase only at acidic pH in vitro, in E. coli cells, and on the mammalian cell surface. We further demonstrated that abFP-tagged δ opioid receptors were fluorescently imaged in lysosome showing distinct features and without background fluorescence from other cellular regions, whereas EGFP-tagged receptors were invisible in lysosome. This Qui-rendered cationic chromophore strategy may be generally applied to other fluorescent proteins to generate a palette of colors for acidic imaging with minimal background, and these abFPs should facilitate the study of molecules in association with various acidic vesicles and organelles in different cells and model organisms.
- Published
- 2018
32. [Advances in the mouse models of myeloid leukemia]
- Author
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Chentao, Ge and Caiyun, Fu
- Subjects
Disease Models, Animal ,Leukemia, Myeloid, Acute ,Mice ,综 述 ,Animals ,Humans - Abstract
Mouse animal models are the most commonly used experimental tools in scientific research, which have been widely favored by researchers. The animal model of mouse leukemia appeared in the 1930s. During the past 90 years, researchers have developed various types of mouse leukemia models to simulate the development and treatment of human leukemia in order to promote effectively the elucidation of the molecular mechanism of leukemia' development and progression, as well as the development of targeted drugs for the treatment of leukemia. Considering that to myeloid leukemia, especially acute myeloid leukemia, there currently is no good clinical treatment, it is urgent to clarify its new molecular mechanism and develop new therapeutic targets. This review focuses on the various types of mouse models about myeloid leukemia used commonly in recent years, including mouse strains, myeloid leukemia cell types, and modeling methods, which are expected to provide a reference for relevant researchers to select animal models during myeloid leukemia research.小鼠动物模型作为科学研究中最常用的实验工具,在两个世纪的发展中受到了研究人员的广泛青睐。小鼠白血病动物模型出现于 20 世纪 30 年代,在近 90 年的发展过程中,研究者们开发出了多种类型的小鼠白血病模型来模拟人类白血病的发生发展和药物治疗过程,这在一定程度上推动了白血病发生发展分子机制的阐明和靶向治疗白血病药物的研发进程。考虑到髓系白血病,特别是急性髓系白血病目前在临床上没有很好的治疗措施,急需阐明其新的分子机制和开发新的治疗靶点,本文重点综述了近几年最常用的髓系白血病小鼠模型,包括小鼠品系、髓系白血病细胞类型、成模方式等,以期为相关科研工作者在髓系白血病研究过程中选择动物模型时提供一定的参考。.
- Published
- 2019
33. Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload
- Author
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Qi Chen, Xi Wang, Liangjue Liu, Caiyun Fu, Feiyan Huang, Zhou Hanwei, Ge Chentao, Hongzhang Wu, Jian Kang, Yue Shi, Yanfang Sun, Hemiao Huang, Yihai Cao, Tianxin Yang, Teng-Fei Zhang, and Richard B. Pearson
- Subjects
Adult ,Male ,Programmed cell death ,Myeloid ,Medical Sciences ,Apoptosis ,Mitochondrion ,Substance P ,mitochondrial calcium fluxes ,medicine.disease_cause ,Mice ,Neurokinin-1 Receptor Antagonists ,hemic and lymphatic diseases ,Cell Line, Tumor ,Calcium flux ,medicine ,Animals ,Humans ,oxidative stress ,Aged ,Inflammation ,Mice, Inbred ICR ,Multidisciplinary ,Leukemia ,Chemistry ,Myeloid leukemia ,Middle Aged ,Receptors, Neurokinin-1 ,Biological Sciences ,medicine.disease ,Mitochondria ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,PNAS Plus ,Cancer research ,Calcium ,Female ,Signal transduction ,Oxidative stress ,Signal Transduction ,neurokinin-1 receptor - Abstract
Significance Despite tremendous efforts in developing effective therapeutics for treating acute myeloid leukemia (AML), this hematological disease remains an incurable malignancy. Here, we show surprising findings that neurokinin-1 receptor (NK-1R) is highly expressed in AML patients and that targeting NK-1R produced potent proapoptotic and antinociceptive effects. Given the clinical availability of the NK-1R antagonists for treating chemotherapy-induced adverse effects, the therapeutic effect of the NK-1R antagonists could be readily tested in human patients with myeloid leukemia. If the therapeutic effect is successfully validated in human patients, our findings would bring hope and benefits for millions of patients. Our study provides another example of drug discovery by mechanistic efforts., Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitochondrial function, a mechanism underlying the cytotoxicity of NK-1R antagonists. Besides anticancer activity, blocking NK-1R produces a potent antinociceptive effect in myeloid leukemia-induced bone pain by alleviating inflammation and inducing apoptosis. These findings thus raise the exciting possibility that the NK-1R antagonists, drugs currently used in the clinic for preventing chemotherapy-induced nausea and vomiting, may provide a therapeutic option for treating human myeloid leukemia.
- Published
- 2019
34. Organoid-derived C-Kit+/SSEA4− human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents
- Author
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Qiyou Li, Siyu Chen, Ting Zou, Xisu Hu, Lixiong Gao, Yuxiao Zeng, Zheng Qin Yin, Yijian Li, Haiwei Xu, Xi Chen, and Caiyun Fu
- Subjects
0301 basic medicine ,Retinal degeneration ,Male ,Stage-Specific Embryonic Antigens ,medicine.medical_treatment ,Human Embryonic Stem Cells ,General Physics and Astronomy ,02 engineering and technology ,Cell Separation ,Mice, SCID ,chemistry.chemical_compound ,Mice ,lcsh:Science ,Multidisciplinary ,Microglia ,Retinal Degeneration ,Cell Differentiation ,Stem-cell therapy ,021001 nanoscience & nanotechnology ,Flow Cytometry ,Cell biology ,Organoids ,Proto-Oncogene Proteins c-kit ,medicine.anatomical_structure ,Treatment Outcome ,Female ,0210 nano-technology ,Cell Survival ,Science ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,medicine ,Animals ,Humans ,Photoreceptor Cells ,Regeneration (biology) ,Gene Expression Profiling ,Retinal ,General Chemistry ,medicine.disease ,Embryonic stem cell ,Coculture Techniques ,Rats ,Transplantation ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Cell culture ,lcsh:Q ,Stem Cell Transplantation - Abstract
Stem cell therapy may replace lost photoreceptors and preserve residual photoreceptors during retinal degeneration (RD). Unfortunately, the degenerative microenvironment compromises the fate of grafted cells, demanding supplementary strategies for microenvironment regulation. Donor cells with both proper regeneration capability and intrinsic ability to improve microenvironment are highly desired. Here, we use cell surface markers (C-Kit+/SSEA4−) to effectively eliminate tumorigenic embryonic cells and enrich retinal progenitor cells (RPCs) from human embryonic stem cell (hESC)-derived retinal organoids, which, following subretinal transplantation into RD models of rats and mice, significantly improve vision and preserve the retinal structure. We characterize the pattern of integration and materials transfer following transplantation, which likely contribute to the rescued photoreceptors. Moreover, C-Kit+/SSEA4− cells suppress microglial activation, gliosis and the production of inflammatory mediators, thereby providing a healthier host microenvironment for the grafted cells and delaying RD. Therefore, C-Kit+/SSEA4− cells from hESC-derived retinal organoids are a promising therapeutic cell source., Stem cell transplantation to treat retinal degeneration could be limited by the degenerative microenvironment. Here, the authors show that C-Kit+/SSEA4– progenitor cells enriched from human embryonic stem cell derived retinal organoids protect retinal structure, suppress microglial activation, gliosis and inflammation.
- Published
- 2019
35. A small interfering RNA targeting vascular endothelial growth factor efficiently inhibits growth of VX2 cells and VX2 tumor model of hepatocellular carcinoma in rabbit by transarterial embolization-mediated siRNA delivery
- Author
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Yu Zou, Zheng-Gang Yang, Min-Ming Zhang, Caiyun Fu, Jun-hui Sun, and Chuan-gen Guo
- Subjects
0301 basic medicine ,CT scan ,Vascular Endothelial Growth Factor A ,Small interfering RNA ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Pharmaceutical Science ,Antineoplastic Agents ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,Drug Delivery Systems ,microvessel density ,In vivo ,Drug Discovery ,medicine ,Tumor Cells, Cultured ,Animals ,Viability assay ,RNA, Small Interfering ,VEGF-siRNAs ,Original Research ,Cell Proliferation ,Pharmacology ,Drug Design, Development and Therapy ,Dose-Response Relationship, Drug ,business.industry ,toxicity to the livers and kidneys ,Liver Neoplasms ,Transfection ,hepatocellular carcinoma ,medicine.disease ,Vascular endothelial growth factor ,Reverse transcription polymerase chain reaction ,Disease Models, Animal ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Toxicity ,Cancer research ,Rabbits ,Drug Screening Assays, Antitumor ,business - Abstract
Yu Zou,1,2 Chuan-Gen Guo,2 Zheng-Gang Yang,3 Jun-Hui Sun,4 Min-Ming Zhang,5 Cai-Yun Fu6,71Department of Radiology, Women’s Hospital, School of Medicine, Zhejiang University, 2Department of Radiology, First Affiliated Hospital, School of Medicine, Zhejiang University, 3Institute of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, 4Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 5Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 6College of Life Sciences, Zhejiang Sci-Tech University, 7Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, People’s Republic of China Introduction: Hepatocellular carcinoma is currently the second leading cause of cancer-related deaths worldwide with an increasing incidence.Objective: The objective of this study is to investigate the effect of vascular endothelial growth factor small interfering RNA (VEGF-siRNA) on rabbit VX2 carcinoma cell viability in vitro and the effect of transarterial embolization (TAE)-mediated VEGF-siRNA delivery on the growth of rabbit VX2 liver-transplanted model in vivo.Methods: Quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot technologies were used to detect the expression level of VEGF. TAE and computed tomography scan were used to deliver the VEGF-siRNA and detect the tumor volume in vivo, respectively. Microvessel density was detected by immunohistochemistry with CD34 antibody. A biochemical autoanalyzer was used to evaluate the hepatic and renal toxicity.Results: The designed VEGF-siRNAs could effectively decrease the expression levels of VEGF mRNA and protein in vitro and in vivo. In vitro, the viability of rabbit VX2 carcinoma cells was reduced by 38.5%±7.3% (VEGF-siRNA no 1) and 30.0%±5.8% (VEGF-siRNA no 3) at 48hours after transfection. Moreover, in rabbit VX2 liver-transplanted model, the growth ratios of tumors at 28days after TAE-mediated siRNA delivery were 155.18%±19.42% in the control group, 79.67%±19.63% in the low-dose group, and 36.09%±15.73% in the high-dose group, with significant differences among these three groups. Microvessel density dropped to 34.22±4.01 and 22.63±4.07 in the low-dose group and high-dose group, respectively, compared with the control group (57.88±5.67), with significant differences among these three groups. Furthermore, inoculation of VX2 tumor into the liver itself at later stage induced significant increase in alanine aminotransferase and aspartate aminotransferase, indicating an obvious damage of liver functions, while treatment of VX2 tumor via TAE-mediated VEGF-siRNA had no toxicity to the livers and kidneys of rabbits, and VEGF-siRNA had the ability to protect liver damage induced by tumor growth.Conclusion: This is the first study to demonstrate that targeting VEGF via TAE-mediated siRNA delivery may become a powerful new option for effective treatment of hepatocellular carcinoma in the clinic.Keywords: hepatocellular carcinoma, VEGF-siRNAs, CT scan, microvessel density, toxicity to the livers and kidneys
- Published
- 2016
36. The independence of and associations among apoptosis, autophagy, and necrosis
- Author
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Caiyun Fu, Jian Kang, and Qi Chen
- Subjects
0301 basic medicine ,Cancer Research ,Programmed cell death ,Necrosis ,lcsh:R ,Cell ,Autophagy ,lcsh:Medicine ,Cancer ,Review Article ,Cell fate determination ,Biology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,Apoptosis ,Genetics ,medicine ,Signal transduction ,medicine.symptom ,lcsh:QH301-705.5 ,Neuroscience - Abstract
Cell death is an essential biological process for physiological growth and development. Three classical forms of cell death—apoptosis, autophagy, and necrosis—display distinct morphological features by activating specific signaling pathways. With recent research advances, we have started to appreciate that these cell death processes can cross-talk through interconnecting, even overlapping, signaling pathways, and the final cell fate is the result of the interplay of different cell death programs. This review provides an insight into the independence of and associations among these three types of cell death and explores the significance of cell death under the specific conditions of human diseases, particularly neurodegenerative diseases and cancer., Targeting the interconnections of cell death to treat disease New understandings of the interconnectivity of cell death pathways could provide novel therapeutic targets for cancer and neurodegenerative diseases like Alzheimer’s. Caiyun Fu of China’s Zhejiang Sci-Tech University and colleagues reviewed the latest research into the mechanisms and connections between the different types of cell death. Apoptosis, ‘programmed’ cell death; necrosis, ‘accidental’ cell death; and autophagy, the means by which cells destroy damaged internal organelles, each has independent molecular mechanisms that can also be simultaneously activated, operating in parallel in response to stress. Targeting these interconnected mechanisms with drugs could treat neurodegenerative diseases like Alzheimer’s and Parkinson’s, in which deregulated cell death plays a major role, and cancer, in which highly proliferating cells escape death pathways.
- Published
- 2018
37. Genetically Encoding Fluorosulfate-l-tyrosine To React with Lysine, Histidine, and Tyrosine via SuFEx in Proteins in Vivo
- Author
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Jun Liu, Nanxi Wang, Peng George Wang, Caiyun Fu, Cheng Ma, Qian Wang, Bing Yang, Feng Zheng, Lei Wang, Tomonori Kobayashi, Shanshan Li, and He Zhu
- Subjects
Models, Molecular ,Lysine ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Catalysis ,Article ,Fluorides ,Colloid and Surface Chemistry ,In vivo ,Models ,medicine ,Humans ,Histidine ,Tyrosine ,Escherichia coli ,chemistry.chemical_classification ,Molecular Structure ,010405 organic chemistry ,Escherichia coli Proteins ,Molecular ,Proteins ,General Chemistry ,Sulfuric Acids ,Genetic code ,0104 chemical sciences ,Amino acid ,HEK293 Cells ,chemistry ,Covalent bond ,Genetic Code ,Hela Cells ,Chemical Sciences ,Sulfur ,HeLa Cells - Abstract
Introducing new chemical reactivity into proteins in living cells would endow innovative covalent bonding ability to proteins for research and engineering in vivo. Latent bioreactive unnatural amino acids (Uaas) can be incorporated into proteins to react with target natural amino acid residues via proximity-enabled reactivity. To expand the diversity of proteins amenable to such reactivity in vivo, a chemical functionality that is biocompatible and able to react with multiple natural residues under physiological conditions is highly desirable. Here we report the genetic encoding of fluorosulfate-l-tyrosine (FSY), the first latent bioreactive Uaa that undergoes sulfur-fluoride exchange (SuFEx) on proteins in vivo. FSY was found nontoxic to Escherichia coli and mammalian cells; after being incorporated into proteins, it selectively reacted with proximal lysine, histidine, and tyrosine via SuFEx, generating covalent intraprotein bridge and interprotein cross-link of interacting proteins directly in living cells. The proximity-activatable reactivity, multitargeting ability, and excellent biocompatibility of FSY will be invaluable for covalent manipulation of proteins in vivo. Moreover, genetically encoded FSY hereby empowers general proteins with the next generation of click chemistry, SuFEx, which will afford broad utilities in chemical biology, drug discovery, and biotherapeutics.
- Published
- 2018
38. Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses
- Author
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Ting Zou, Xiaoli Liu, Zehua Chen, Zheng Qin Yin, Xi Chen, Haiwei Xu, Yuxiao Zeng, Chen Zhao, Zhengya Li, and Caiyun Fu
- Subjects
0301 basic medicine ,Retinal degeneration ,Pathology ,genetic structures ,Cell- and Tissue-Based Therapy ,Medicine (miscellaneous) ,Cell therapy ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Synapse formation ,Cells, Cultured ,Neurons ,Neuronal Plasticity ,Stem Cells ,Retinal Degeneration ,Cell Differentiation ,Cell biology ,medicine.anatomical_structure ,Differentiation ,Molecular Medicine ,Stem cell ,Photoreceptor Cells, Vertebrate ,medicine.medical_specialty ,Lewis X Antigen ,Biology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Retina ,03 medical and health sciences ,medicine ,Animals ,Progenitor cell ,Cell Proliferation ,Transplantation ,Retinal pigment epithelium ,Research ,Retinal ,Cell Biology ,medicine.disease ,eye diseases ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,c-kit ,Synapses ,Neuroplasticity ,sense organs ,030217 neurology & neurosurgery ,Stem Cell Transplantation - Abstract
Background Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Methods Eye-wall c-kit+/stage-specific embryonic antigen 1 (SSEA1)− cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit+/SSEA1− cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Results Eye-wall c-kit+/SSEA1− cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit+/SSEA1− cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit+/SSEA1− cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit+/SSEA1− cells were capable of differentiating into functional photoreceptors that formed new synaptic connections with recipient retinas in rd1 mice. Transplantation also partially corrected the abnormalities of inner retina of rd1 mice. At 4 and 8 weeks post transplantation, the rd1 mice that received c-kit+/SSEA1− cells showed significant increases in a-wave and b-wave amplitude and the percentage of time spent in the dark area. Conclusions Grafted c-kit+/SSEA1− cells restored the retinal function of rd1 mice via regulating neural plasticity and forming new graft-to-host synapses.
- Published
- 2016
39. Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel
- Author
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Lu Yan, Xia Ruilong, Caiyun Fu, Shi-Fu Zhang, Zhao Fukun, and Zhu Lina
- Subjects
Cancer Research ,Programmed cell death ,Paclitaxel ,Cell ,Apoptosis ,Biology ,chemistry.chemical_compound ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Humans ,Cell Proliferation ,Leukemia ,Cell growth ,General Medicine ,Cell cycle ,medicine.disease ,Antineoplastic Agents, Phytogenic ,medicine.anatomical_structure ,Oncology ,chemistry ,Cancer research ,M Phase Cell Cycle Checkpoints ,Cell Division ,K562 cells - Abstract
Paclitaxel, one of the broadest-spectrum anticancer agents, is currently being used in the treatment of patients with solid tumors. In the present study, we compared the effect of paclitaxel on two types of leukemia cells. Our results showed that paclitaxel could inhibit the proliferation of MEL and K562 cells in a dose- and time-dependent manner. The mechanism of proliferative inhibition in K562 cells treated by paclitaxel was related to the cell cycle arrest in the G2/M phase, as well as the induction of apoptosis. By contrast, MEL cells treated by paclitaxel showed significant characteristics of necrosis, which indicated that the mode of cell death induced by paclitaxel in these two types of leukemia cells differed. Advances in research of the cell cycle, apoptosis and necrosis will extend our understanding of the mechanisms of paclitaxel-induced cell death, particularly in leukemia cells. Further elucidation of the mechanisms of necrosis in MEL cells may expedite the development of improved paclitaxel-based regimens for cancer therapy.
- Published
- 2013
40. Study on the distribution sites and the molecular mechanism of analgesia after intracerebroventricular injection of rat/mouse hemokinin-1 in mice
- Author
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Yuanting Jin, Caiyun Fu, Xia Ruilong, Zhao Fukun, and Shi-Fu Zhang
- Subjects
Male ,medicine.medical_specialty ,Pro-Opiomelanocortin ,Physiology ,medicine.drug_class ,Narcotic Antagonists ,Endogeny ,Peptide ,Biochemistry ,Mice ,Cellular and Molecular Neuroscience ,Endocrinology ,Neurokinin-1 Receptor Antagonists ,Proopiomelanocortin ,Opioid receptor ,Tachykinins ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Receptor ,chemistry.chemical_classification ,Mice, Inbred ICR ,Messenger RNA ,biology ,Antagonist ,Receptors, Neurokinin-1 ,Infusions, Intraventricular ,Opioid Peptides ,chemistry ,Receptors, Opioid ,biology.protein ,Female ,NK1 receptor antagonist ,Analgesia - Abstract
Hemokinin-1 is a peptide encoded by Pptc, which belongs to the family of mammalian tachykinins. Our previous results showed that rat/mouse hemokinin-1 (r/m HK-1) produced striking analgesia after intracerebroventricular (i.c.v.) injection in mice, and the analgesia could be blocked by the NK1 receptor antagonist and the opioid receptor antagonist, respectively. However, the precise distribution sites and the molecular mechanism involved in the analgesic effect after i.c.v. administration of r/m HK-1 are needed to be further investigated deeply. Using the fluorescence labeling method, our present results directly showed that r/m HK-1 peptides were mainly distributed at the ventricular walls and several juxta-ventricular structures for the first time. Our results showed that the mRNA expressions of NK1 receptor, PPT-A, PPT-C, KOR, PDYN, DOR and PENK were not changed markedly, as well as the protein expression of NK1 receptor was hardly changed. However, both the transcripts and proteins of MOR and POMC were up-regulated significantly, indicating that the analgesic effect induced by i.c.v. administration of r/m HK-1 is related to the activation of NK1 receptor first, then it is related to the release of endogenous proopiomelanocortin, as well as the increased expression level of μ opioid receptor. These results should facilitate further the analysis of the analgesia of r/m HK-1 in the central nerval system in acute pain and may open novel pharmacological interventions.
- Published
- 2013
41. Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells
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Qiyou Li, Ting Zou, Haiwei Xu, Qian Wu, Zheng Qin Yin, Xi Chen, Siyu Chen, Yuxiao Zeng, Lixiong Gao, and Caiyun Fu
- Subjects
0301 basic medicine ,Retinal Ganglion Cells ,Cellular differentiation ,Human Embryonic Stem Cells ,Embryoid body ,Biology ,Retinal ganglion ,Epithelium ,Retina ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Movement ,medicine ,Humans ,Cells, Cultured ,Embryoid Bodies ,Cell Proliferation ,Neural Plate ,Multidisciplinary ,Retinal ,Cell Differentiation ,Embryonic stem cell ,Cell biology ,Oxygen ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Immunology ,Stem cell ,Neural plate ,Biomarkers - Abstract
The vertebrate retina is a highly multilayered nervous tissue with a large diversity of cellular components. With the development of stem cell technologies, human retinas can be generated in three-dimensional (3-D) culture in vitro. However, understanding the factors modulating key productive processes and the way that they influence development are far from clear. Oxygen, as the most essential element participating in metabolism, is a critical factor regulating organic development. In this study, using 3-D culture of human stem cells, we examined the effect of intermittent high oxygen treatment (40% O2) on the formation and cellular behavior of neural retinas (NR) in the embryonic body (EB). The volume of EB and number of proliferating cells increased significantly under 40% O2 on day 38, 50 and 62. Additionally, the ratio of PAX6+ cells within NR was significantly increased. The neural rosettes could only develop with correct apical-basal polarity under 40% O2. In addition, the generation, migration and maturation of retinal ganglion cells were enhanced under 40% O2. All of these results illustrated that 40% O2 strengthened the formation of NR in EB with characteristics similar to the in vivo state, suggesting that the hyperoxic state facilitated the retinal development in vitro.
- Published
- 2016
42. PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells
- Author
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Bu-Yun Wei, Yue Shi, Zhou Hanwei, Qi Chen, Lu Yan, Caiyun Fu, Y. Eugene Chinn, Teng-Fei Zhang, Tianxin Yang, Xi Wang, and Jian Kang
- Subjects
0301 basic medicine ,Programmed cell death ,Cell Survival ,Antimicrobial peptides ,Peptide ,Antineoplastic Agents ,Apoptosis ,HL-60 Cells ,Biology ,Hemolysis ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Necrosis ,0302 clinical medicine ,Annexin ,Lactoferricin ,Cell Line, Tumor ,Animals ,Humans ,Cytotoxicity ,Cell Proliferation ,chemistry.chemical_classification ,Multidisciplinary ,Leukemia ,Cell Cycle ,Molecular biology ,Disease Models, Animal ,Lactoferrin ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Female ,Peptides ,Intracellular ,Antimicrobial Cationic Peptides - Abstract
LF11-322 (PFWRIRIRR-NH2) (PFR peptide), a nine amino acid-residue peptide fragment derived from human lactoferricin, possesses potent cytotoxicity against bacteria. We report here the discovery and characterization of its antitumor activity in leukemia cells. PFR peptide inhibited the proliferation of MEL and HL-60 leukemia cells by inducing cell death in the absence of the classical features of apoptosis, including chromatin condensation, Annexin V staining, Caspase activation and increase of abundance of pro-apoptotic proteins. Instead, necrotic cell death as evidenced by increasing intracellular PI staining and LDH release, inducing membrane disruption and up-regulating intracellular calcium level, was observed following PFR peptide treatment. In addition to necrotic cell death, PFR peptide also induced G0/G1 cell cycle arrest. Moreover, PFR peptide exhibited favorable antitumor activity and tolerability in vivo. These findings thus provide a new clue of antimicrobial peptides as a potential novel therapy for leukemia.
- Published
- 2016
- Full Text
- View/download PDF
43. Advances in cancer pain from bone metastasis
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Ti-Fei Yuan, Jia-Li Zhang, Yuan-Yang Yu, Caiyun Fu, Xiao-Cui Zhu, Pan Wang, and Chen-Tao Ge
- Subjects
Oncology ,Pain Threshold ,medicine.medical_specialty ,molecular mechanisms ,Pharmaceutical Science ,Bone Neoplasms ,Review ,Malignancy ,Quality of life ,Internal medicine ,Threshold of pain ,Drug Discovery ,medicine ,Animals ,Humans ,Pain Management ,Molecular Targeted Therapy ,Bone pain ,animal models of cancer pain ,Pain Measurement ,Pharmacology ,Analgesics ,business.industry ,Breakthrough Pain ,Cancer ,Bone metastasis ,drug treatment ,Pain Perception ,medicine.disease ,cancer pain from bone metastasis ,Surgery ,Disease Models, Animal ,Treatment Outcome ,Quality of Life ,Calcaneus ,medicine.symptom ,Diffusion of Innovation ,Cancer pain ,business ,Signal Transduction - Abstract
With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models.
- Published
- 2015
44. Analgesic effects of lappaconitine in leukemia bone pain in a mouse model
- Author
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Yuan-Yang Yu, Xiao-Cui Zhu, Jia-Li Zhang, Chen-Tao Ge, Caiyun Fu, and Pan Wang
- Subjects
Pathology ,medicine.medical_specialty ,Analgesic ,lcsh:Medicine ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Bone pain ,Medicine ,Tibia ,Endogenous opioid ,Leukemia ,Animal Behavior ,business.industry ,General Neuroscience ,lcsh:R ,Cancer ,General Medicine ,medicine.disease ,XIAP ,Lappaconitine ,medicine.symptom ,Analgesia ,General Agricultural and Biological Sciences ,business ,K562 cells ,Neuroscience - Abstract
Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR), as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53). Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.
- Published
- 2015
45. Effects of [Nphe1]nociceptin(1-13)NH2, [Phe1(CH2-NH)Gly2]nociceptin(1- 13)NH2, and Nocistatin on Nociceptin Inhibited Constrictions of Guinea Pig Isolated Bronchus
- Author
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Peng Yali, Rui Wang, Qi Yang, Yong Chen, Min Chang, and Caiyun Fu
- Subjects
Male ,medicine.medical_specialty ,Stereochemistry ,Guinea Pigs ,Bronchi ,Biochemistry ,Guinea pig ,Structural Biology ,Internal medicine ,medicine ,Animals ,Electric field stimulation ,Receptor ,Bronchus ,Morphine ,Chemistry ,General Medicine ,Electric Stimulation ,Peptide Fragments ,Nociceptin receptor ,medicine.anatomical_structure ,Endocrinology ,Opioid Peptides ,Excitatory postsynaptic potential ,Cholinergic ,Female ,medicine.drug - Abstract
Electric field stimulation (EFS) causes excitatory non adrenergic-non cholinergic (eNANC) and cholinergic constrictions in the guinea pig isolated bronchus, the activation of eNANC and cholinergic nerves respectively. We investigated the effects of [Nphe1]nociceptin(1-13)NH2 ([Nphe1]NC(1-13)NH2), [Phe1(CH2-NH)Gly2]nociceptin(1- 13)NH2 ([F/G] NC(1-13)NH2), and nocistatin (NST) on nociceptin (NC) inhibited constrictions in isolated bronchus of guinea pig. The results show that NC (1 micromol/L) inhibited EFS-induced eNANC and cholinergic constrictions compared with the control, in which nociceptin was not applied. After pretreatment with [Nphe1]NC(1-13)NH2, [F/G]NC(1-13)NH2, or NST, the inhibitions of NC were antagonized by [Nphe1]NC(1-13)NH2 and [F/G]NC(1-13)NH2 but not NST. However, [Nphe1]NC(1-13)NH2, [F/G]NC(1-13)NH2, and NST did not affect the inhibitions induced by morphine. Furthermore, [Nphe1]NC(1-13)NH2, [F/G]NC(1-13)NH2 and NST did not cause any appreciable effects on EFS-induced eNANC and cholinergic constrictions in guinea pig bronchi. The results demonstrate that [Nphe1]NC(1-13)NH2 and [F/G]NC(1- 13)NH2 but not NST act as selective antagonists of the NC receptor and the effects of NC on EFS-induced constrictions of guinea pig isolated bronchus.
- Published
- 2006
46. Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.
- Author
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Chentao Ge, Hemiao Huang, Feiyan Huang, Tianxin Yang, Tengfei Zhang, Hongzhang Wu, Hanwei Zhou, Qi Chen, Yue Shi, Yanfang Sun, Liangjue Liu, Xi Wang, Pearson, Richard B., Yihai Cao, Jian Kang, and Caiyun Fu
- Subjects
OXIDATIVE stress ,MYELOID leukemia ,LEUKEMIA ,ACUTE myeloid leukemia ,LEUCOCYTES - Abstract
Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitochondrial function, a mechanism underlying the cytotoxicity of NK-1R antagonists. Besides anticancer activity, blocking NK-1R produces a potent antinociceptive effect in myeloid leukemia-induced bone pain by alleviating inflammation and inducing apoptosis. These findings thus raise the exciting possibility that the NK-1R antagonists, drugs currently used in the clinic for preventing chemotherapyinduced nausea and vomiting, may provide a therapeutic option for treating human myeloid leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
47. Genetically Encoding Fluorosulfate-L-tyrosine To React with Lysine, Histidine, and Tyrosine via SuFEx in Proteins in Vivo.
- Author
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Nanxi Wang, Bing Yang, Caiyun Fu, He Zhu, Feng Zheng, Tomonori Kobayashi, Jun Liu, Shanshan Li, Cheng Ma, Wang, Peng G., Qian Wang, and Lei Wang
- Published
- 2018
- Full Text
- View/download PDF
48. The complete mitochondrial genome ofPhrynocephalus guinanensis(Reptilia, Squamata, Agamidae)
- Author
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Yuanting Jin, Wei Chen, and Caiyun Fu
- Subjects
0301 basic medicine ,Mitochondrial DNA ,Squamata ,RNA, Mitochondrial ,Molecular Sequence Data ,Zoology ,Agamidae ,Mitochondrial Proteins ,03 medical and health sciences ,Monophyly ,RNA, Transfer ,Gene Order ,Genetics ,Animals ,Molecular Biology ,Gene ,Phylogeny ,Base Sequence ,Phylogenetic tree ,biology ,Lizards ,Ribosomal RNA ,biology.organism_classification ,Sexual dimorphism ,030104 developmental biology ,RNA, Ribosomal ,Evolutionary biology ,Genome, Mitochondrial ,RNA - Abstract
Recent phylogenetic researches discovered no reciprocal monophyly between morphological species of Phrynocephalus putjatia and P. guinanensis, P. guinanensis exhibits extensive sexual color dimorphism, whereas P. putjatia does not have. The complete mitochondrial genome of the putative taxa, Phrynocephalus guinanensis, was determined in order to compare the mitogenomes of both ecological forms. The mitogenome sequence was 16,279 bp in size. It consists of 13 protein-coding, 22 tRNA, 2 rRNA genes and 3 control region, and its gene order and gene content were identical with the mitogenome of P. putjatia.
- Published
- 2014
49. Grafted c-kit+/SSEA1- eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses.
- Author
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Xi Chen, Zehua Chen, Zhengya Li, Chen Zhao, Caiyun Fu, Xiaoli Liu, Haiwei Xu, and Zheng Qin Yin
- Subjects
RETINAL degeneration ,PHOTORECEPTORS ,PROGENITOR cells ,NEUROPLASTICITY ,CELL transplantation ,FLOW cytometry ,IMMUNOCHEMISTRY ,SYNAPTOPHYSIN - Abstract
Background: Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Methods: Eye-wall c-kitD
+ /stage-specific embryonic antigen 1 (SSEA1)- cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kitD+ /SSEA1- cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Results: Eye-wall c-kitD+ /SSEA1- cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kitD+ /SSEA1- cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kitD+ /SSEA1- celltransplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kitD+ /SSEA1- cells were capable of differentiating into functional photoreceptors that formed new synaptic connections with recipient retinas in rd1 mice. Transplantation also partially corrected the abnormalities of inner retina of rd1 mice. At 4 and 8 weeks post transplantation, the rd1 mice that received c-kitD+ /SSEA1- cells showed significant increases in a-wave and b-wave amplitude and the percentage of time spent in the dark area. Conclusions: Grafted c-kitD+ /SSEA1- cells restored the retinal function of rd1 mice via regulating neural plasticity and forming new graft-to-host synapses. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
50. Hemokinin-1(4-11)-Induced Analgesia Selectively Up-Regulates δ-Opioid Receptor Expression in Mice
- Author
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Lu Yan, Tao Jin, Xiao-Zhou Mou, Caiyun Fu, Teng-Fei Zhang, Shi-Fu Zhang, Zhi-Qiang Yu, and Xia Ruilong
- Subjects
Central Nervous System ,Male ,Anatomy and Physiology ,Pro-Opiomelanocortin ,medicine.drug_class ,Cognitive Neuroscience ,Blotting, Western ,Central nervous system ,Receptors, Opioid, mu ,lcsh:Medicine ,Pain ,Gene Expression ,Pharmacology ,Neurological System ,Behavioral Neuroscience ,Downregulation and upregulation ,Anesthesiology ,Opioid receptor ,Naltrindole ,Receptors, Opioid, delta ,Tachykinins ,Gene expression ,medicine ,Pain Management ,Animals ,Humans ,Protein Precursors ,lcsh:Science ,Receptor ,Biology ,Injections, Intraventricular ,Mice, Inbred ICR ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,lcsh:R ,Antagonist ,Animal Cognition ,Peptide Fragments ,Up-Regulation ,medicine.anatomical_structure ,Neurology ,Opioid ,Medicine ,lcsh:Q ,Female ,Analgesia ,Research Article ,Neuroscience ,medicine.drug - Abstract
Our previous studies have shown that an active fragment of human tachykinins (hHK-1(4-11)) produced an opioid-independent analgesia after intracerebroventricular (i.c.v.) injection in mice, which has been markedly enhanced by a δ OR antagonist, naltrindole hydrochloride (NTI). In this study, we have further characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11) in mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK) have not changed significantly. Furthermore, neither transcription nor expression of NK1 receptor, MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels of DOR have been up-regulated significantly, indicating that the enhanced expression of δ opioid receptor negatively modulates the analgesia induced by i.c.v. injection of hHK-1(4-11). Additionally, the combinatorial data from our previous and present experiments strongly suggest that the discriminable distribution sites in the central nervous system between hHK-1(4-11) and r/mHK-1 may be attributed to their discriminable analgesic effects. Altogether, our findings will not only contribute to the understanding of the complicated mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its active fragments at supraspinal level, but may also lead to novel pharmacological interventions.
- Published
- 2014
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