90 results on '"Lisha Mou"'
Search Results
2. Facile construction of the stable layer on the surface of Si/C electrode assisted by SWCNT coating
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Zenghua Chang, Lisha Mou, Zechao Shao, Mei Ou, Tianchi Fan, Bin Li, Shuaijin Wu, Rennian Wang, and Jiantao Wang
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Electrochemistry ,General Materials Science ,Electrical and Electronic Engineering ,Condensed Matter Physics - Published
- 2023
3. Construction of a lipid metabolism-related risk model for hepatocellular carcinoma by single cell and machine learning analysis
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Lisha Mou, Zuhui Pu, Yongxiang Luo, Ryan Quan, Yunhu So, and Hui Jiang
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Immunology ,Immunology and Allergy - Abstract
One of the most common cancers is hepatocellular carcinoma (HCC). Numerous studies have shown the relationship between abnormal lipid metabolism-related genes (LMRGs) and malignancies. In most studies, the single LMRG was studied and has limited clinical application value. This study aims to develop a novel LMRG prognostic model for HCC patients and to study its utility for predictive, preventive, and personalized medicine. We used the single-cell RNA sequencing (scRNA-seq) dataset and TCGA dataset of HCC samples and discovered differentially expressed LMRGs between primary and metastatic HCC patients. By using the least absolute selection and shrinkage operator (LASSO) regression machine learning algorithm, we constructed a risk prognosis model with six LMRGs (AKR1C1, CYP27A1, CYP2C9, GLB1, HMGCS2, and PLPP1). The risk prognosis model was further validated in an external cohort of ICGC. We also constructed a nomogram that could accurately predict overall survival in HCC patients based on cancer status and LMRGs. Further investigation of the association between the LMRG model and somatic tumor mutational burden (TMB), tumor immune infiltration, and biological function was performed. We found that the most frequent somatic mutations in the LMRG high-risk group were CTNNB1, TTN, TP53, ALB, MUC16, and PCLO. Moreover, naïve CD8+ T cells, common myeloid progenitors, endothelial cells, granulocyte-monocyte progenitors, hematopoietic stem cells, M2 macrophages, and plasmacytoid dendritic cells were significantly correlated with the LMRG high-risk group. Finally, gene set enrichment analysis showed that RNA degradation, spliceosome, and lysosome pathways were associated with the LMRG high-risk group. For the first time, we used scRNA-seq and bulk RNA-seq to construct an LMRG-related risk score model, which may provide insights into more effective treatment strategies for predictive, preventive, and personalized medicine of HCC patients.
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- 2023
4. Construction of a novel predictive model with seven metabolism-related genes for hepatocellular carcinoma by machine learning
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Lisha Mou, Lin Liu, Yumiao Qiu, Yingying Liang, and Zuhui Pu
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Cell Biology ,Molecular Biology ,Biochemistry ,Genetics (clinical) - Published
- 2023
5. The transcriptome profile of RPE cells by the fullerenol against hydrogen peroxide stress
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Xiaojun, Wu, Fuwen, Yao, Jing-Ying, Xu, Jiao, Chen, Ying, Lu, Wei, Li, Jing, Deng, Lisha, Mou, Qingling, Zhang, and Zuihui, Pu
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General Medicine - Abstract
Age-related macular degeneration (AMD) causes central vision impairment with increased incidence. In the pathogenesis of AMD, reactive oxygen species (ROS) are associated with RPE cell apoptosis. H2O2 is an oxidative toxicant and is used to establish the AMD in vitro model. However, the mechanisms of ROS in H2O2-induced AMD are still unclear. Fullerenol, a promising antioxidant of nanomaterials, protects RPE cells from ROS attack. In addition to working as a scavenger, little is known about the antioxidant mechanism of fullerenol in RPE cells. In this study, transcriptome sequencing was performed to examine the global changes in mRNA transcripts induced by H2O2 in human ARPE-19 cells. Moreover, we comprehensively investigated the protective effects of fullerenol against H2O2-induced oxidative injury by RNA sequencing. Gene Ontology enrichment analysis showed that those pathways related to the release of positive regulation of DNA-templated transcription and negative regulation of apoptotic process were affected. Finally, we found that 12 hub genes were related to the oxidative-protection function of fullerenol. In summary, H2O2 affected these hub genes and signaling pathways to regulate the senescence of RPE cells. Moreover, fullerenol is a potent nanomaterial that protects the RPE and would be a promising approach for AMD prevention.
- Published
- 2022
6. Clinical and Prognostic Value of
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Lisha, Mou, Chenyang, Jia, Zijing, Wu, Boyang, Xin, Carmen Alicia, Liang Zhen, Bailiang, Wang, Yong, Ni, and Zuhui, Pu
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Gene Expression Regulation, Neoplastic ,Carcinoma, Hepatocellular ,Chemokine CCL20 ,Pyrimidines ,Purines ,Gene Expression Profiling ,Liver Neoplasms ,Sequestosome-1 Protein ,Humans ,Peptidylprolyl Isomerase ,Single-Cell Analysis ,Prognosis - Abstract
Hepatocellular carcinoma (HCC) is the most malignant and poor-prognosis subtype of primary liver cancer. The scRNA-seq approach provides unique insight into tumor cell behavior at the single-cell level. Cytokine signaling in the immune system plays an important role in tumorigenesis and has both pro-tumorigenic and anti-tumorigenic functions. A biomarker of cytokine signaling in immune-related genes (CSIRG) is urgently required to assess HCC patient diagnosis and treatment. By analyzing the expression profiles of HCC single cells, TCGA, and ICGC data, we discovered that three important CSIRG (
- Published
- 2022
7. Multi-View Mammographic Density Classification by Dilated and Attention-Guided Residual Learning
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Cheng Li, Zuhui Pu, Yongjin Zhou, Qiegen Liu, Hairong Zheng, Shanshan Wang, Xu Jingxu, Yong Xia, and Lisha Mou
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Computer science ,Feature extraction ,Breast Neoplasms ,Residual ,Machine learning ,computer.software_genre ,Deep Learning ,Breast cancer ,Image Interpretation, Computer-Assisted ,Genetics ,medicine ,Humans ,Mammography ,Breast ,Network architecture ,medicine.diagnostic_test ,business.industry ,Applied Mathematics ,Deep learning ,Image segmentation ,medicine.disease ,ComputingMethodologies_PATTERNRECOGNITION ,Task analysis ,Female ,Artificial intelligence ,business ,computer ,Biotechnology - Abstract
Breast density is widely adopted to reflect the likelihood of early breast cancer development. Existing methods of mammographic density classification either require steps of manual operations or achieve only moderate classification accuracy due to the limited model capacity. In this study, we present a radiomics approach based on dilated and attention-guided residual learning for the task of mammographic density classification. The proposed method was instantiated with two datasets, one clinical dataset and one publicly available dataset, and classification accuracies of 88.7 and 70.0 percent were obtained, respectively. Although the classification accuracy of the public dataset was lower than the clinical dataset, which was very likely related to the dataset size, our proposed model still achieved a better performance than the naive residual networks and several recently published deep learning-based approaches. Furthermore, we designed a multi-stream network architecture specifically targeting at analyzing the multi-view mammograms. Utilizing the clinical dataset, we validated that multi-view inputs were beneficial to the breast density classification task with an increase of at least 2.0 percent in accuracy and the different views lead to different model classification capacities. Our method has a great potential to be further developed and applied in computer-aided diagnosis systems. Our code is available at https://github.com/lich0031/Mammographic_Density_Classification .
- Published
- 2021
8. Human IL-17 and TNF-α Additively or Synergistically Regulate the Expression of Proinflammatory Genes, Coagulation-Related Genes, and Tight Junction Genes in Porcine Aortic Endothelial Cells
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Weilong Li, Pengfei Chen, Yanli Zhao, Mengtao Cao, Wenjun Hu, Litao Pan, Huimin Sun, Dongsheng Huang, Hanxi Wu, Zhuoheng Song, Huanli Zhong, Lisha Mou, Shaodong Luan, Xiehui Chen, and Hanchao Gao
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Interleukin-6 ,Swine ,Tumor Necrosis Factor-alpha ,Histocompatibility Antigens Class I ,Interleukin-17 ,Immunology ,Histocompatibility Antigens Class II ,Animals ,Cytokines ,Endothelial Cells ,Humans ,Immunology and Allergy ,Tight Junctions - Abstract
Immune rejection is the major limitation for porcine xenograft survival in primate recipients. Proinflammatory cytokines play important roles in immune rejection and have been found to mediate the pathological effects in various clinical and experimental transplantation trials. IL-17 and TNF-α play critical pathological roles in immune disorders, such as psoriasis and rheumatoid arthritis. However, the pathological roles of human IL-17 (hIL-17) and human TNF-α (hTNF-α) in xenotransplantation remain unclear. Here we found that hIL-17 and hTNF-α additively or synergistically regulate the expression of 697 genes in porcine aortic endothelial cells (PAECs). Overall, 415 genes were found to be synergistically regulated, while 282 genes were found to be additively regulated. Among these, 315 genes were upregulated and 382 genes were downregulated in PAECs. Furthermore, we found that hIL-17 and hTNF-α additively or synergistically induced the expression of various proinflammatory cytokines and chemokines (e.g., IL1α, IL6, and CXCL8) and decreased the expression of certain anti-inflammatory genes (e.g., IL10). Moreover, hIL-17 plus hTNF-α increased the expression of IL1R1 and IL6ST, receptors for IL1 and IL6, respectively, and decreased anti-inflammatory gene receptor expression (IL10R). hIL-17 and hTNF-α synergistically or additively induced CXCL8 and CCL2 expression and consequently promoted primary human neutrophil and human leukemia monocytic cell migration, respectively. In addition, hIL-17 and hTNF-α induced pro-coagulation gene (SERPINB2 and F3) expression and decreased anti-coagulation gene (TFPI, THBS1, and THBD) expression. Additionally, hIL-17 and hTNF-α synergistically decreased occludin expression and consequently promoted human antibody-mediated complement-dependent cytotoxicity. Interestingly, hTNF-α increased swine leukocyte antigen (SLA) class I expression; however, hIL-17 decreased TNF-α-mediated SLA-I upregulation. We concluded that hIL-17 and hTNF-α likely promote the inflammatory response, coagulation cascade, and xenoantibody-mediated cell injury. Thus, blockade of hIL-17 and hTNF-α together might be beneficial for xenograft survival in recipients.
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- 2022
9. Current Topics of Relevance to the Xenotransplantation of Free Pig Islets
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Lisha Mou, Guanghan Shi, David K.C. Cooper, Ying Lu, Jiao Chen, Shufang Zhu, Jing Deng, Yuanyuan Huang, Yong Ni, Yongqiang Zhan, Zhiming Cai, and Zuhui Pu
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endocrine system ,Diabetes Mellitus, Type 1 ,endocrine system diseases ,Transplantation, Heterologous ,Immunology ,Islets of Langerhans Transplantation ,Animals ,Humans ,Immunology and Allergy ,CD40 Antigens ,Immunosuppressive Agents - Abstract
Pig islet xenotransplantation is a potential treatment for patients with type 1 diabetes. Current efforts are focused on identifying the optimal pig islet source and overcoming the immunological barrier. The optimal age of the pig donors remains controversial since both adult and neonatal pig islets have advantages. Isolation of adult islets using GMP grade collagenase has significantly improved the quantity and quality of adult islets, but neonatal islets can be isolated at a much lower cost. Certain culture media and coculture with mesenchymal stromal cells facilitate neonatal islet maturation and function. Genetic modification in pigs affords a promising strategy to prevent rejection. Deletion of expression of the three known carbohydrate xenoantigens (Gal, Neu5Gc, Sda) will certainly be beneficial in pig organ transplantation in humans, but this is not yet proven in islet transplantation, though the challenge of the ‘4th xenoantigen’ may prove problematic in nonhuman primate models. Blockade of the CD40/CD154 costimulation pathway leads to long-term islet graft survival (of up to 965 days). Anti-CD40mAbs have already been applied in phase II clinical trials of islet allotransplantation. Fc region-modified anti-CD154mAbs successfully prevent the thrombotic complications reported previously. In this review, we discuss (I) the optimal age of the islet-source pig, (ii) progress in genetic modification of pigs, (iii) the immunosuppressive regimen for pig islet xenotransplantation, and (iv) the reduction in the instant blood-mediated inflammatory reaction.
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- 2022
10. The Lineage Differentiation and Dynamic Heterogeneity of Thymic Epithelial Cells During Thymus Organogenesis
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Hanchao, Gao, Mengtao, Cao, Kai, Deng, Yang, Yang, Jinqi, Song, Ming, Ni, Chuntao, Xie, Wenna, Fan, Chunpei, Ou, Dinggen, Huang, Lizhong, Lin, Lixia, Liu, Yangyang, Li, Huimin, Sun, Xinyu, Cheng, Jinmei, Wu, Cuilan, Xia, Xuefeng, Deng, Lisha, Mou, and Pengfei, Chen
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Mice ,Organogenesis ,Immunology ,Animals ,Immunology and Allergy ,Cell Differentiation ,Cell Lineage ,Epithelial Cells ,Thymus Gland ,Antigens ,Phosphoproteins ,Glycoproteins - Abstract
Although much progress has been made recently in revealing the heterogeneity of the thymic stromal components, the molecular programs of cell lineage divergency and temporal dynamics of thymic epithelial cell (TEC) development are largely elusive. Here, we constructed a single-cell transcriptional landscape of non-hematopoietic cells from mouse thymus spanning embryonic to adult stages, producing transcriptomes of 30,959 TECs. We resolved the transcriptional heterogeneity of developing TECs and highlighted the molecular nature of early TEC lineage determination and cortico-medullary thymic epithelial cell lineage divergency. We further characterized the differentiation dynamics of TECs by clarification of molecularly distinct cell states in the thymus developing trajectory. We also identified a population of Bpifa1+ Plet1+ mTECs that was preserved during thymus organogenesis and highly expressed tissue-resident adult stem cell markers. Finally, we highlighted the expression of Aire-dependent tissue-restricted antigens mainly in Aire+ Csn2+ mTECs and Spink5+ Dmkn+ mTECs in postnatal thymus. Overall, our data provided a comprehensive characterization of cell lineage differentiation, maturation, and temporal dynamics of thymic epithelial cells during thymus organogenesis.
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- 2022
11. Transcriptomic profiling of long non-coding RNAs in non-virus associated hepatocellular carcinoma
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Zhiwu Lv, Yongqiang Zhan, Lisha Mou, Haosheng Liu, Liu Lu, Chen He, Jintao Liu, Yong Ni, and Ganlu Wang
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0301 basic medicine ,Carcinoma, Hepatocellular ,Biophysics ,Biology ,Biochemistry ,Transcriptome ,Pathogenesis ,03 medical and health sciences ,Downregulation and upregulation ,Gene expression ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Messenger ,Gene ,030102 biochemistry & molecular biology ,Gene Expression Profiling ,Liver Neoplasms ,Cell Biology ,General Medicine ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Tumor progression ,Hepatocellular carcinoma ,Cancer research ,RNA, Long Noncoding ,Viral hepatitis - Abstract
Due to falling prevalence of viral hepatitis (VH), obesity, alcoholism and related liver diseases have become increasingly frequent and important as causes of hepatocellular carcinoma (HCC). However, mechanisms underlying hepatocarcinogenesis and tumor progression in VH-negative HCC remain poorly understood. Long non-coding RNAs (lncRNAs) have been implicated in pathogenesis of human diseases, including HCC. Here, by analyzing 20 clinical samples' RNA-sequencing data generated from 8 VH-negative and 2 VH-positive HCC patients, we have identified and characterized 1,514 candidate lncRNAs. For differentially expressed genes (DEGs) between tumor tissues and adjacent non-tumor tissues (P 0.05, |FC| 2), the upregulated genes were mainly involved in the cell proliferation, and the downregulated genes mediated the metabolic processes and responses to oxidative stress, inflammation and toxic substances. Furthermore, the lncRNA-mRNA co-expression network was constructed, by which two genetic aberrations with high frequency in HCC, SPATA46 and TMEM78, were identified. In addition, we identified 16 DEGs between tumor issues from VH-negative and VH-positive HCC patients with aim to explore gene expression differences that could be involved in the pathogenesis of HCC with varying etiology. In conclusion, we performed the comprehensive analysis of lncRNA and mRNA expression profiles, which could provide valuable insights into the underlying genetic alteration in non-virus associated HCC.
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- 2020
12. Generation of rat blood vasculature and hematopoietic cells in rat-mouse chimeras by blastocyst complementation
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Liangxue Lai, Lisha Mou, Yangyang Suo, Hui Shi, Xiaomin Wang, Shixue Gou, Chengdan Lai, Nana Fan, Zhen Ouyang, Quanjun Zhang, Chen Pengfei, Qingjian Zou, Quanmei Yan, and Juanjuan Zhou
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Pluripotent Stem Cells ,Major histocompatibility complex ,Mice ,03 medical and health sciences ,Chimera (genetics) ,0302 clinical medicine ,Genetics ,medicine ,Animals ,Blastocyst ,Yolk sac ,Induced pluripotent stem cell ,Molecular Biology ,Embryonic Stem Cells ,030304 developmental biology ,0303 health sciences ,biology ,Chimera ,Hematopoietic Stem Cell Transplantation ,Embryo Transfer ,Hematopoietic Stem Cells ,Embryonic stem cell ,Rats ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,biology.protein ,Blood Vessels ,Stem cell ,030217 neurology & neurosurgery - Abstract
Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells. A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs. Therefore, to achieve a transplantable organ in animals without rejection, creation of vascular endothelial cells derived from humans within the organ is necessary. In this study, to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals, we generated rat-mouse chimeras by injection of rat embryonic stem cells (rESCs) into mouse blastocysts with deficiency of Flk-1 protein, which is associated with endothelial and hematopoietic cell development. We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras. The whole yolk sac (YS) of Flk-1EGFP/EGFP rat-mouse chimera was full of rat blood vasculature. Rat genes related to vascular endothelial cells, arteries, and veins, blood vessels formation process, as well as hematopoietic cells, were highly expressed in the YS. Our results suggested that rat vascular endothelial cells could undergo proliferation, migration, and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells, T cells, and myeloid cells in rat-mouse chimeras, which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse.
- Published
- 2020
13. Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin
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Hidetaka Hara, Yifan Dai, Hu Wenbao, Ying Lu, Lisha Mou, Zhiming Cai, and Liu Zhengzhao
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Medicine (General) ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,nonhuman primate ,Glucagon ,R5-920 ,STZ ,Internal medicine ,Diabetes mellitus ,medicine ,geography ,geography.geographical_feature_category ,business.industry ,Insulin ,analytical grade ,Metabolic acidosis ,Original Articles ,General Medicine ,medicine.disease ,Streptozotocin ,Islet ,Transplantation ,Endocrinology ,Blood chemistry ,Original Article ,diabetic model ,business ,medicine.drug - Abstract
Backgrounds Streptozotocin (STZ)‐ induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs. There are serious side effects of this method, including nausea, emesis, weight loss, liver damage, renal failure, and metabolic acidosis. In order to reduce the side effects, diabetic monkeys were induced using clinical‐grade STZ. However, clinical‐grade STZ is not available in China. Here, we establised a method by using 100 mg/kg analytical‐grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal. Methods Three cynomolgus monkeys were used in this study. 100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein. After the STZ administration, blood glucose levels were examined every 1 or 2 hours in the first 48 hours. Then, blood glucose levels were examined twice per day during the first week after the STZ injection. Insulin and C‐peptide levels were measured by ELISA. Blood chemistry of hepatic and renal function tests were performed. Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays. Results The stimulated C‐peptide level (Intravenous glucose tolerance test) which is less than 0.5 ng/mL, the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model. No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection. Conclusion In summary, we established a safe and reproducible STZ‐induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.
- Published
- 2020
14. Development of cationic polymer-based nanoplatform for insulin delivery and diabetes treatment
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Lisha Mou, Tong Tong, Meng Zhao, and Qi Lou
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Materials science ,Insulin delivery ,Cationic polymerization ,General Materials Science ,Pharmacology ,Diabetes treatment - Abstract
Due to the high molecular weight, hydrophilicity, and pH/enzyme sensitivity of proteins, effectively delivery of therapeutic proteins remains many difficulties. In this study, a novel nanoplatform for insulin delivery was established, in which a kind of tunable cationic polymer based on arginine was chosen as the nanocarrier. The nanocomplexes were formed with the cationic polymers and insulin under the electrostatic reactions. Then the relationship between the chemical structure of polymers and physicochemical properties of nanocomplex was systematically investigated among the particle size, surface charge, cytotoxicity, cellular internalization ability and finally therapeutic effects. It was confirmed that the structure of polymers affected their hydrophobicity, subsequently influencing the physicochemical properties of nanocomplex and further the therapeutic effects of nanocomplex. The in vivo results also proved that the suitable polymer with an optimal weight ratio of materials and proteins could obtain a promising therapeutic effect on Type 1 diabetes.
- Published
- 2020
15. Association between Aldose Reductase Gene C(-106)T Polymorphism and Diabetic Retinopathy: A Systematic Review and Meta-Analysis
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Zuhui Pu, Ruiting Chen, Shan Lin, Zhiming Cai, Lisha Mou, Jiying Hu, Mengtao Cao, and Yuanzheng Peng
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medicine.medical_specialty ,Genotype ,Cochrane Library ,Lower risk ,Polymorphism, Single Nucleotide ,Gastroenterology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Gene Frequency ,Aldehyde Reductase ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,Aldose reductase ,Diabetic Retinopathy ,business.industry ,DNA ,General Medicine ,Diabetic retinopathy ,medicine.disease ,Sensory Systems ,Ophthalmology ,Meta-analysis ,030221 ophthalmology & optometry ,business ,030217 neurology & neurosurgery - Abstract
Controversial results regarding the associations between aldose reductase (AR) genetic polymorphisms and diabetic retinopathy (DR) have been reported for many years. The present meta-analysis was performed to clarify the effects of the AR gene C(-106)T polymorphism on DR risk. The PubMed, Web of Sciences, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure, and Wan Fang databases were extensively searched in Chinese to select relevant studies with an updated date of April 25, 2018. The Newcastle-Ottawa Scale (NOS) was applied to assess quality. The random-effects model was applied to calculate the pooled OR and 95% CI. This meta-analysis identified 23 studies with an average score of 7.52 for NOS analysis, including 4,313 DR cases and 5,128 diabetes mellitus (DM) control cases. In the overall analysis, a significant association between the AR gene C(-106)T polymorphism and DR susceptibility was found. In subgroups stratified by DM type and ethnicity, significantly increased risks for DR were found in DM type 1, East Asian populations, and Middle Eastern populations. Compared with DR control cases, the following associations were found: T vs. C: OR 0.91, 95% CI 0.85–0.97, I2 = 72.9%; CT + TT vs. CC: OR 0.75, 95% CI 0.68–0.81, I2 = 86.7%; and CT vs. CC: OR 0.86, 95% CI 0.78–0.94, I2 = 70.5%. The results of this meta-analysis showed a significant association between the AR gene C(-106)T polymorphism and susceptibility to DR in DM patients. DM patients with allele T and CT+TT genotype of the AR gene may have a lower risk of DR.
- Published
- 2020
16. Screening and Identification of the First Non-CRISPR/Cas9-Treated Chinese Miniature Pig With Defective Porcine Endogenous Retrovirus pol Genes
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Yuyuan Ma, Junting Jia, Rui Fan, Ying Lu, Xiong Zhao, Yadi Zhong, Jierong Yang, Limin Ma, Yanlin Wang, Maomin Lv, Haiyuan Yang, Lisha Mou, Yifan Dai, Shutang Feng, and Jingang Zhang
- Subjects
China ,Transcription, Genetic ,Swine ,Transplantation, Heterologous ,whole-genome resequencing ,Immunology ,Gene Products, pol ,inbreeding ,full-length transcriptome sequencing ,Genome, Viral ,defective gene ,Cell Line ,Proviruses ,Animals ,Humans ,Immunology and Allergy ,Amino Acid Sequence ,porcine endogenous retrovirus ,Cells, Cultured ,Original Research ,Genome ,Sequence Homology, Amino Acid ,Gene Expression Profiling ,Endogenous Retroviruses ,Chinese miniature pig ,RC581-607 ,Genes, pol ,HEK293 Cells ,Swine, Miniature ,Immunologic diseases. Allergy - Abstract
Pig to human xenotransplantation is considered to be a possible approach to alleviate the shortage of human allografts. Porcine endogenous retrovirus (PERV) is the most significant pathogen in xenotransplantation. We screened for pigs that consistently did not transmit human-tropic replication competent PERVs (HTRC PERVs), namely, non-transmitting pigs. Then, we conducted whole-genome resequencing and full-length transcriptome sequencing to further investigate the sequence characteristics of one non-transmitting pig. Using in vitro transmission assays, we found 5 (out of 105) pigs of the Chinese Wuzhishan minipig inbred line that did not transmit PERV to human cells, i.e., non-transmitting pigs. Whole-genome resequencing and full-length transcriptome sequencing of one non-transmitting pig showed that all of the pol genes were defective at both the genome and transcript levels. We speculate that the defective PERV pol genes in this pig might be attributable to the long-term inbreeding process. This discovery is promising for the development of a strain of highly homozygous and genetically stable pigs with defective PERV pol genes as a source animal species for xenotransplantation.
- Published
- 2022
17. Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft
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Pengfei Chen, Fuwen Yao, Ying Lu, Yuanzheng Peng, Shufang Zhu, Jing Deng, Zijing Wu, Jiao Chen, Kai Deng, Qi Li, Zuhui Pu, and Lisha Mou
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Mice ,Isografts ,Immunology ,Histocompatibility Antigens Class I ,Islets of Langerhans Transplantation ,Immunology and Allergy ,Animals ,Humans ,Transplantation, Homologous ,CD8-Positive T-Lymphocytes ,Allografts - Abstract
Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8+ T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.
- Published
- 2022
18. Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis
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Murad Alahdal, Chang Chongfei, Xiong Jianyi, Lisha Mou, Chen Jinfu, Yiyun Geng, Weimin Zhu, Li Duan, Manyi Wang, and Daping Wang
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Cartilage, Articular ,Male ,0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Osteoarthritis ,Mesenchymal Stem Cell Transplantation ,Injections, Intra-Articular ,Umbilical Cord ,Rats, Sprague-Dawley ,Extracellular matrix ,03 medical and health sciences ,Chondrocytes ,0302 clinical medicine ,Endocrinology ,Animals ,Humans ,Regeneration ,Medicine ,Orthopedics and Sports Medicine ,business.industry ,Cartilage ,Regeneration (biology) ,Lentivirus ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,General Medicine ,Transfection ,Chondrogenesis ,medicine.disease ,Disease Models, Animal ,MicroRNAs ,medicine.anatomical_structure ,Cancer research ,030101 anatomy & morphology ,Stem cell ,business - Abstract
Currently, osteoarthritis (OA) receives global increasing attention because it associates severe joint pain and serious disability. Stem cells intra-articular injection therapy showed a potential therapeutic superiority to reduce OA development and to improve treating outputs. However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. Recently, miR-140-5p was confirmed as a critical positive regulator in chondrogenesis. We hypothesized that hUC-MSCs overexpressing miR-140-5p have better therapeutic effect on osteoarthritis. To enhance stem cell chondrogenic differentiation, we have transfected human umbilical cord mesenchymal stem cells (hUC-MSCs) with miR-140-5p mimics and miR-140-5p lentivirus to overexpress miR-140-5p in a short term or a long term accordingly. Thereafter, MSCs proliferation, chondrogenic genes expression and extracellular matrix were assessed. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of SD rats as an OA model, and then intra-articular injection of hUC-MSCs or hUC-MSCs transfected with miR-140-5p lentivirus was carried to evaluate the cartilage healing effect with histological staining and OARSI scores. The localization of hUC-MSCs after intra-articular injection was further confirmed by immunohistochemical staining. Significant induction of chondrogenic differentiation in the miR-140-5p-hUC-MSCs (140-MSCs), while its proliferation was not influenced. Interestingly, intra-articular injection of 140-MSCs significantly enhanced articular cartilage self-repairing in comparison to normal hUC-MSCs. Moreover, we noticed that intra-articular injection of high 140-MSCs numbers reinforces cells assembling on the impaired cartilage surface and subsequently differentiated into chondrocytes. In conclusion, these results indicate therapeutic superiority of hUC-MSCs overexpressing miR-140-5p to treat OA using intra-articular injection.
- Published
- 2019
19. Adult Pig Islet Isolation
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Jing Deng, Yongqiang Zhan, Wenlong Huang, Lisha Mou, Ying Lu, Zuhui Pu, Rita Bottino, Chunliang Xu, Zhiming Cai, Zijing Wu, Ying Deng, Jun Cheng, Fuwen Yao, Naiyang Zhan, Yong Ni, Shufang Zhu, and Jiao Chen
- Subjects
endocrine system ,endocrine system diseases ,Swine ,General Chemical Engineering ,medicine.medical_treatment ,Cell ,Transplantation, Heterologous ,Islets of Langerhans Transplantation ,Hypoglycemic episodes ,General Biochemistry, Genetics and Molecular Biology ,Islets of Langerhans ,Mice ,medicine ,Animals ,Pancreas ,Type 1 diabetes ,geography ,geography.geographical_feature_category ,General Immunology and Microbiology ,business.industry ,General Neuroscience ,Insulin ,medicine.disease ,Islet ,Transplantation ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,Immunology ,business ,Allotransplantation - Abstract
Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of pancreatic β cells, which results in little or no insulin production. Islet transplantation plays an important role in the treatment of T1DM, with the improved glycometabolic control, the reduced progression of complications, the reduction of hypoglycemic episodes when compared with traditional insulin therapy. The results of phase III clinical trial also demonstrated the safety and efficacy of islet allotransplantation in T1DM. However, the shortage of pancreas donors limits its widespread use. Animals as a source of islets such as the pig offer an alternative choice. Because the architecture of the pig pancreas is different from the islets of mice or humans, the pig islet isolation procedure is still challenging. Since the translation of alternative porcine islet sources (xenogeneic) to the clinical setting for treating T1DM through cellular transplantation is of great importance, a cost-effective, standardized, and reproducible protocol for isolating porcine islets is urgently needed. This manuscript describes a simplified and cost-effective method to isolate and purify adult porcine islets based on the previous protocols that have successfully transplanted porcine islets to non-human primates. This will be a beginners guide without the use of specialized equipment such as a COBE 2991 Cell Processor.
- Published
- 2021
20. LncRNAs Target Ferroptosis-Related Genes and Impair Activation of CD4
- Author
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Fuwen, Yao, Yongqiang, Zhan, Zuhui, Pu, Ying, Lu, Jiao, Chen, Jing, Deng, Zijing, Wu, Binhua, Chen, Jinjun, Chen, Kuifeng, Tian, Yong, Ni, and Lisha, Mou
- Subjects
Cell and Developmental Biology ,long non-coding RNAs ,lncRNA ,CD4+ T cell activation ,immune infiltration ,gastric cancer ,tumor microenvironment ,TCGA ,ferroptosis ,Original Research - Abstract
Gastric cancer (GC) is a malignant disease of the digestive tract and a life-threatening disease worldwide. Ferroptosis, an iron-dependent cell death caused by lipid peroxidation, is reported to be highly correlated with gastric tumorigenesis and immune cell activity. However, the underlying relationship between ferroptosis and the tumor microenvironment in GC and potential intervention strategies have not been unveiled. In this study, we profiled the transcriptome and prognosis data of ferroptosis-related genes (FRGs) in GC samples of the TCGA-STAD dataset. The infiltrating immune cells in GC were estimated using the CIBERSORT and XCELL algorithms. We found that the high expression of the hub FRGs (MYB, PSAT1, TP53, and LONP1) was positively correlated with poor overall survival in GC patients. The results were validated in an external GC cohort (GSE62254). Further immune cell infiltration analysis revealed that CD4+ T cells were the major infiltrated cells in the tumor microenvironment of GC. Moreover, the hub FRGs were significantly positively correlated with activated CD4+ T cell infiltration, especially Th cells. The gene features in the high-FRG score group were enriched in cell division, DNA repair, protein folding, T cell receptor, Wnt and NIK/NF-kappaB signaling pathways, indicating that the hub FRGs may mediate CD4+ T cell activation by these pathways. In addition, an upstream transcriptional regulation network of the hub FRGs by lncRNAs was also developed. Three lncRNAs (A2M-AS1, C2orf27A, and ZNF667-AS1) were identified to be related to the expression of the hub FRGs. Collectively, these results showed that lncRNA A2M-AS1, C2orf27A, and ZNF667-AS1 may target the hub FRGs and impair CD4+ T cell activation, which finally leads to poor prognosis of GC. Effective interventions for the above lncRNAs and the hub FRGs can help promote CD4+ T cell activation in GC patients and improve the efficacy of immunotherapy. These findings provide a novel idea of GC immunotherapy and hold promise for future clinical application.
- Published
- 2021
21. Improving Outcomes of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: New Data and Ongoing Trials
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Lisha Mou, Xiaohe Tian, Bo Zhou, Yongqiang Zhan, Jiao Chen, Ying Lu, Jing Deng, Ying Deng, Zijing Wu, Qi Li, Yi’an Song, Hongyuan Zhang, Jinjun Chen, Kuifeng Tian, Yong Ni, and Zuhui Pu
- Subjects
Sorafenib ,Drug ,Cancer Research ,media_common.quotation_subject ,medicine.medical_treatment ,Review ,lenvatinib ,Drug resistance ,Targeted therapy ,chemistry.chemical_compound ,tyrosine kinase inhibitors ,Medicine ,HCC ,RC254-282 ,media_common ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,hepatocellular carcinoma ,targeted therapy ,medicine.disease ,respiratory tract diseases ,Clinical trial ,TKIs ,Oncology ,chemistry ,Hepatocellular carcinoma ,Cancer research ,sorafenib ,business ,Lenvatinib ,Tyrosine kinase ,medicine.drug - Abstract
Targeted therapies such as oral tyrosine kinase inhibitors (TKIs) are the main therapeutic strategy effective for advanced hepatocellular carcinoma (HCC). Currently six tyrosine kinase inhibitors for HCC therapy have been approved. The newly approved first-line drug donafenib represent the major milestones in HCC therapeutics in recent years. However, drug resistance in HCC remains challenging due to random mutations in target receptors as well as downstream pathways. TKIs-based combinatorial therapies with immune checkpoint inhibitors such as PD-1/PD-L1 antibodies afford a promising strategy to further clinical application. Recent developments of nanoparticle-based TKI delivery techniques improve drug absorption and bioavailability, enhance efficient targeting delivery, prolonged circulation time, and reduce harmful side effects on normal tissues, which may improve the therapeutic efficacy of the TKIs. In this review, we summarize the milestones and recent progress in clinical trials of TKIs for HCC therapy. We also provide an overview of the novel nanoparticle-based TKI delivery techniques that enable efficient therapy.
- Published
- 2021
22. Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients
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Yiyun Geng, Jinfu Chen, Chongfei Chang, Yifen Zhang, Li Duan, Weimin Zhu, Lisha Mou, Jianyi Xiong, and Daping Wang
- Subjects
ceRNA network ,human bone marrow mesenchymal stem cells ,non-coding RNA ,Genetics ,Molecular Medicine ,QH426-470 ,Genetics (clinical) ,senile osteoporosis ,whole transcriptome sequencing ,Original Research - Abstract
Senile osteoporosis (SOP) is a worldwide age-related disease characterized by the loss of bone mass and decrease in bone strength. Bone mesenchymal stem cells (BMSCs) play an important role in the pathology of senile osteoporosis. Abnormal expression and regulation of non-coding RNA (ncRNA) are involved in a variety of human diseases. In the present study, we aimed to identify differentially expressed mRNAs and ncRNAs in senile osteoporosis patient-derived BMSCs via high-throughput transcriptome sequencing in combination with bioinformatics analysis. As a result, 415 mRNAs, 30 lncRNAs, 6 circRNAs and 27 miRNAs were found to be significantly changed in the senile osteoporosis group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to analyze the function of differentially expressed mRNAs and ncRNAs. The circRNA–miRNA–mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Interestingly, circRNA008876-miR-150-5p-mRNA was the sole predicted circRNA-miRNA-mRNA network. The differential expression profile of this ceRNA network was further verified by qRT-PCR. The biological function of this network was validated by overexpression and knockdown experiments. In conclusion, circRNA008876-miR-150-5p-mRNA could be an important ceRNA network involved in senile osteoporosis, which provides potential biomarkers and therapeutic targets for senile osteoporosis.
- Published
- 2021
23. Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice
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Rita Bottino, Zuhui Pu, Ying Lu, Hanchen Zhang, Zhicheng Zou, Yuanzheng Peng, Lisha Mou, Liang Sun, Zhoubin Fang, Shan Lin, Zhiming Cai, Michael F. Knoll, Jiao Chen, Chuanghua Qiu, Mengtao Cao, and Yifan Dai
- Subjects
Blood Glucose ,Male ,endocrine system diseases ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Glycemic Control ,Ribotyping ,Streptozocin ,Diabetes Mellitus, Experimental ,Pathogenesis ,Tissue Culture Techniques ,Feces ,medicine ,Animals ,Hypoglycemic Agents ,Insulin ,Alistipes ,Autoimmune disease ,Transplantation ,Type 1 diabetes ,geography ,Mice, Inbred BALB C ,geography.geographical_feature_category ,biology ,Bacteria ,business.industry ,Streptozotocin ,medicine.disease ,biology.organism_classification ,Islet ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Diabetes Mellitus, Type 1 ,Immunology ,Dysbiosis ,business ,Biomarkers ,medicine.drug - Abstract
Background Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear. Methods In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition. Results The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM. Conclusions Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.
- Published
- 2021
24. Clinical and Prognostic Value of PPIA, SQSTM1, and CCL20 in Hepatocellular Carcinoma Patients by Single-Cell Transcriptome Analysis
- Author
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Lisha Mou, Chenyang Jia, Zijing Wu, Boyang Xin, Carmen Alicia Liang Zhen, Bailiang Wang, Yong Ni, and Zuhui Pu
- Subjects
hepatocellular carcinoma ,HCC ,scRNA-seq ,single cell ,cytokine signaling in immune ,prediction model ,immune microenvironment ,TMB ,GSEA ,General Medicine - Abstract
Hepatocellular carcinoma (HCC) is the most malignant and poor-prognosis subtype of primary liver cancer. The scRNA-seq approach provides unique insight into tumor cell behavior at the single-cell level. Cytokine signaling in the immune system plays an important role in tumorigenesis and has both pro-tumorigenic and anti-tumorigenic functions. A biomarker of cytokine signaling in immune-related genes (CSIRG) is urgently required to assess HCC patient diagnosis and treatment. By analyzing the expression profiles of HCC single cells, TCGA, and ICGC data, we discovered that three important CSIRG (PPIA, SQSTM1, and CCL20) were linked to the overall survival of HCC patients. Cancer status and three hub CSIRG were taken into account while creating a risk nomogram. The nomogram had a high level of predictability and accuracy. Based on the CSIRG risk score, a distinct pattern of somatic tumor mutational burden (TMB) was detected between the two groups. The enrichment of the pyrimidine metabolism pathway, purine metabolism pathway, and lysosome pathway in HCC was linked to the CSIRG high-risk scores. Overall, scRNA-seq and bulk RNA-seq were used to create a strong CSIRG signature for HCC diagnosis.
- Published
- 2022
25. Multimedia resource allocation strategy of wireless sensor networks using distributed heuristic algorithm in cloud computing environment
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Jian Yang, Shumu Liu, Zhen Xiang, and Lisha Mou
- Subjects
Network architecture ,Computer Networks and Communications ,Computer science ,business.industry ,Distributed computing ,Network virtualization ,Cloud computing ,Virtualization ,computer.software_genre ,Hardware and Architecture ,Distributed algorithm ,Media Technology ,Resource allocation ,Network performance ,business ,Wireless sensor network ,computer ,Software - Abstract
The virtualized resource allocation (mapping) algorithm is the core issue of network virtualization technology. Universal and excellent resource allocation algorithms not only provide efficient and reliable network resources sharing for systems and users, but also simplify the complexity of resource scheduling and management, improve the utilization of basic resources, balance network load and optimize network performance. Based on the application of wireless sensor network, this paper proposes a wireless sensor network architecture based on cloud computing. The WSN hardware resources are mapped into resources in cloud computing through virtualization technology, and the resource allocation strategy of the network architecture is proposed. The experiment evaluates the performance of the resource allocation strategy. The proposed heuristic algorithm is a distributed algorithm. The complexity of centralized algorithms is high, distributed algorithms can handle problems in parallel, and reduce the time required to get a good solution with limited traffic.
- Published
- 2019
26. Potential roles of mesenchymal stromal cells in islet allo‐ and xenotransplantation for type 1 diabetes mellitus
- Author
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Ying Lu, Huayi Cao, Jun Chen, Yongqiang Zhan, Naiyang Zhan, Zhiming Cai, Zhenjie Li, Ziwei Tu, David K. C. Cooper, Jiao Chen, Qi Lou, Yong Ni, Yi Zeng, Lisha Mou, Yifan Dai, Zuhui Pu, and Zepeng Qu
- Subjects
0301 basic medicine ,endocrine system ,Stromal cell ,endocrine system diseases ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Immunology ,Islets of Langerhans Transplantation ,030230 surgery ,Mesenchymal Stem Cell Transplantation ,Cell therapy ,Islets of Langerhans ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Transplantation ,geography ,geography.geographical_feature_category ,business.industry ,Regeneration (biology) ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Islet ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,Cancer research ,business ,Allotransplantation - Abstract
Islet transplantation is poised to play an important role in the treatment of type 1 diabetes mellitus (T1DM). However, there are several challenges limiting its widespread use, including the instant blood-mediated inflammatory reaction, hypoxic/ischemic injury, and the immune response. Mesenchymal stem/stromal cells (MSCs) are known to exert regenerative, immunoregulatory, angiogenic, and metabolic properties. Here, we review recent reports on the application of MSCs in islet allo- and xenotransplantation. We also document the clinical trials that have been undertaken or are currently underway, relating to the co-transplantation of islets and MSCs. Increasing evidence indicates that co-transplantation of MSCs prolongs islet graft survival by locally secreted protective factors that reduce immune reactivity and promote vascularization, cell survival, and regeneration. MSC therapy may be a promising option for islet transplantation in patients with T1DM.
- Published
- 2021
27. A self-supervised feature-standardization-block for cross-domain lung disease classification
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Zhongliang Li, Zuhui Pu, Xuechen Li, Heng Kong, Zhihui Lai, Lisha Mou, Wei-cai Dai, Yingqi Li, Min Cao, Linlin Shen, and Juan Yu
- Subjects
Lung Diseases ,0303 health sciences ,Contextual image classification ,Standardization ,Computer science ,business.industry ,Deep learning ,030302 biochemistry & molecular biology ,Pattern recognition ,Reference Standards ,Convolutional neural network ,General Biochemistry, Genetics and Molecular Biology ,Domain (software engineering) ,03 medical and health sciences ,Deep Learning ,Feature (computer vision) ,Computer-aided diagnosis ,Humans ,Artificial intelligence ,Neural Networks, Computer ,business ,Molecular Biology ,Lung ,030304 developmental biology ,Block (data storage) - Abstract
With the advance of deep learning technology, convolutional neural network (CNN) has been wildly used and achieved the state-of-the-art performances in the area of medical image classification. However, most existing medical image classification methods conduct their experiments on only one public dataset. When applying a well-trained model to a different dataset selected from different sources, the model usually shows large performance degradation and needs to be fine-tuned before it can be applied to the new dataset. The goal of this work is trying to solve the cross-domain image classification problem without using data from target domain. In this work, we designed a self-supervised plug-and-play feature-standardization-block (FSB) which consisting of image normalization (INB), contrast enhancement (CEB) and boundary detection blocks (BDB), to extract cross-domain robust feature maps for deep learning framework, and applied the network for chest x-ray-based lung diseases classification. Three classic deep networks, i.e. VGG, Xception and DenseNet and four chest x-ray lung diseases datasets were employed for evaluating the performance. The experimental result showed that when employing feature-standardization-block, all three networks showed better domain adaption performance. The image normalization, contrast enhancement and boundary detection blocks achieved in average 2%, 2% and 5% accuracy improvement, respectively. By combining all three blocks, feature-standardization-block achieved in average 6% accuracy improvement.
- Published
- 2021
28. Electrochemical impedance characteristics at various conditions for commercial solid–liquid electrolyte lithium-ion batteries: Part. 2. Modeling and prediction
- Author
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Fei Feng, Rui Yang, Jinhao Meng, Yi Xie, Zhiguo Zhang, Yi Chai, and Lisha Mou
- Subjects
General Energy ,Mechanical Engineering ,Building and Construction ,Electrical and Electronic Engineering ,Pollution ,Industrial and Manufacturing Engineering ,Civil and Structural Engineering - Published
- 2022
29. Electrochemical impedance characteristics at various conditions for commercial solid–liquid electrolyte lithium-ion batteries: Part 1. experiment investigation and regression analysis
- Author
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Fei Feng, Rui Yang, Jinhao Meng, Yi Xie, Zhiguo Zhang, Yi Chai, and Lisha Mou
- Subjects
General Energy ,Mechanical Engineering ,Building and Construction ,Electrical and Electronic Engineering ,Pollution ,Industrial and Manufacturing Engineering ,Civil and Structural Engineering - Published
- 2022
30. Quantification of Circulating Pig-Specific DNA in the Blood of a Xenotransplantation Model
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Yifan Dai, Jiao Chen, Zuhui Pu, Lisha Mou, Deng Yangyang, Dongjing Yu, Ming Zhou, Ying Lu, and Yongqiang Zhan
- Subjects
Swine ,General Chemical Engineering ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Transplants ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Mice ,Cell transplantation ,Species Specificity ,medicine ,Animals ,Humans ,Immune rejection ,DNA Primers ,Genome ,General Immunology and Microbiology ,business.industry ,General Neuroscience ,Reproducibility of Results ,Haplorhini ,Reference Standards ,Biomarker (cell) ,Organ damage ,Transplantation ,chemistry ,Specific primers ,Immunology ,Models, Animal ,Heterografts ,business ,Cell-Free Nucleic Acids ,DNA - Abstract
Xenotransplantation is a feasible method to treat organ failure. However, how to effectively monitor the immune rejection of xenotransplantation is a problem for physicians and researchers. This manuscript describes a simple and effective method to monitor immune rejection in pig-to-mouse cell transplantation models and pig-to-monkey artery patch transplantation models. Circulating DNA is a potentially non-invasive biomarker for organ damage. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection by quantitative real-time PCR (qPCR). In this protocol, porcine specific primers were designed, plasmids-containing porcine specific DNA fragments were constructed, and standard curves for quantitation were established. Species-specific primers were then used to quantify cpsDNA by qPCR in pig-to-mouse cell transplantation models and pig-to-monkey artery patch transplantation models. The value of this method suggests that it can be used as a simple, convenient, low cost, and less invasive method to monitor the immune rejection of xenotransplantation.
- Published
- 2020
31. Immunosuppressive and metabolic agents that influence allo- and xenograft survival by in vivo expansion of T regulatory cells
- Author
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Wenjun Hu, Shaodong Luan, Yanli Zhao, Ying-Wei Zhang, Hidetaka Hara, Gao Hanchao, Chen Pengfei, David K. C. Cooper, Lisha Mou, Changchun Zeng, and Mengtao Cao
- Subjects
Regulatory T cell ,Xenotransplantation ,medicine.medical_treatment ,Immunology ,Transplantation, Heterologous ,chemical and pharmacologic phenomena ,T-Lymphocytes, Regulatory ,In vivo ,medicine ,Animals ,Humans ,Transplantation ,CD40 ,biology ,Effector ,business.industry ,Graft Survival ,hemic and immune systems ,Immunosuppressive drug ,medicine.anatomical_structure ,Cancer research ,biology.protein ,Heterografts ,Histone deacetylase ,business ,Immunosuppressive Agents - Abstract
The transplanted organs or cells survive if the recipient receives adequate long-term immunosuppressive therapy. Immunosuppressive therapy combined with cell-based strategies (eg, regulatory T cell [Treg]-based therapy) promotes graft survival. A combination of Treg-based therapy and minimal or no immunosuppressive drug therapy would have the potential to minimize the risks of the complications and side effects of these drugs. Fortunately, some immunosuppressive and other agents not only impede the effector T cell response, but also help generate new CD4+ Tregs from conventional effector T cells. These agents include IL-2, TGF-β, agents that block the CD40/CD40L costimulation pathway, mTOR inhibitors, and histone deacetylase inhibitors. Consequently, a state of relative unresponsiveness to the transplanted organ may be induced through the expansion of Tregs. We here review the effect of these various agents on expansion of CD4+ Tregs in allo- and xenotransplantation. The expansion of Tregs might allow a dose reduction of the standard immunosuppressive drugs.
- Published
- 2020
32. Inguinal Subcutaneous White Adipose Tissue (ISWAT) Transplantation Model of Murine Islets
- Author
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David K. C. Cooper, Lisha Mou, Jiao Chen, Yuanzheng Peng, Hongxing Fu, Ying Lu, Hancheng Zhang, Shan Lin, Rito Bittino, Mengtao Cao, Zhicheng Zou, Yifan Dai, and Zhiming Cai
- Subjects
Blood Glucose ,endocrine system ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,General Chemical Engineering ,Islets of Langerhans Transplantation ,Subcutaneous Fat ,Inguinal Canal ,White adipose tissue ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Diabetes Mellitus, Experimental ,Islets of Langerhans ,Diabetes mellitus ,medicine ,Animals ,Humans ,Basement membrane ,Tissue Survival ,geography ,geography.geographical_feature_category ,General Immunology and Microbiology ,business.industry ,General Neuroscience ,Pancreatic islets ,Body Weight ,Graft Survival ,Islet ,medicine.disease ,Transplantation ,Mice, Inbred C57BL ,Perfusion ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,Collagenase ,Pancreatic islet transplantation ,business ,medicine.drug - Abstract
Pancreatic islet transplantation is a well-established therapeutic treatment for type 1 diabetes. The kidney capsule is the most commonly used site for islet transplantation in rodent models. However, the tight kidney capsule limits the transplantation of sufficient islets in large animals and humans. The inguinal subcutaneous white adipose tissue (ISWAT), a new subcutaneous space, was found to be a potentially valuable site for islet transplantation. This site has better blood supply than other subcutaneous spaces. Moreover, the ISWAT accommodates a larger islet mass than the kidney capsule, and transplantation into it is simple. This manuscript describes the procedure of mouse islet isolation and transplantation in the ISWAT site of syngeneic diabetic mouse recipients. Using this protocol, murine pancreatic islets were isolated by standard collagenase digestion and a basement membrane matrix hydrogel was used for fixing the purified islets in the ISWAT site. The blood glucose levels of the recipient mice were monitored for more than 100 days. Islet grafts were retrieved at day 100 after transplantation for histological analysis. The protocol for islet transplantation in the ISWAT site described in this manuscript is simple and effective.
- Published
- 2020
33. Selective inhibition of cyclooxygenase‐2 protects porcine aortic endothelial cells from human antibody‐mediated complement‐dependent cytotoxicity
- Author
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Changchun Zeng, Ying Lu, Jiabao Huang, David K. C. Cooper, Lin Lizhong, Chunpei Ou, Yongqiang Zhan, Jin-qi Song, Huimin Sun, Chen Pengfei, Lisha Mou, Yanli Zhao, Gao Hanchao, Deng Xuefeng, Ze-jin Lin, and Li Yajing
- Subjects
0301 basic medicine ,Small interfering RNA ,Swine ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Immunology ,Apoptosis ,030230 surgery ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,medicine ,Animals ,Propidium iodide ,Aorta ,Inflammation ,Transplantation ,biology ,Tumor Necrosis Factor-alpha ,Chemistry ,NF-kappa B ,Endothelial Cells ,Molecular biology ,Complement-dependent cytotoxicity ,030104 developmental biology ,Cyclooxygenase 2 ,biology.protein ,Cytokines ,Tumor necrosis factor alpha ,Cyclooxygenase - Abstract
Background Cyclooxygenase-2 (COX-2) is an inducible enzyme with catalytic activity for biosynthesis of prostaglandins which are the key mediators of inflammation. COX-2 is also the therapeutic target for widely used non-steroidal anti-inflammatory drugs (NSAIDs). However, the involvement of COX-2 in xenotransplantation (eg, pig-to-non-human primate) remains poorly recognized. Methods We investigated the mechanisms that regulate COX-2 expression and the effects of COX-2 on porcine aortic endothelial cell (PAEC) viability using in vitro pig-to-primate xenotransplantation model and in vivo pig-to-mouse cellular transplant model. Regulation of COX-2 expression was assessed by real-time quantitative polymerase chain reaction (qPCR) and Western blotting. The effects of inhibition or downregulation of COX-2 on PAEC viability were assessed by propidium iodide (PI)-Annexin V staining and Cell Counting Kit-8 assay. Results Human serum triggered robust COX-2 expression in PAECs in a dose- and time-dependent manner. Induction of COX-2 expression by human serum was partially through activation of both canonical and non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κb) signaling and increasing intracellular calcium. Cytokines like tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-17, were able to induce COX-2 expression. Selective inhibition of COX-2 by celecoxib dramatically decreased PAEC death in vitro and in vivo as defined by propidium iodide (PI)-Annexin V staining. Consistently, downregulation of COX-2 expression by NF-κb inhibitors or calcium chelator BAPTA decreased human serum-induced PAEC death as well. Silencing of COX-2 expression by small interfering RNA (siRNA) protected PAEC viability when transplanted under kidney capsule of C57BL/6 mice. Conclusions Taken together, our data suggest that COX-2 is highly induced in PAECs by xenogenic serum and associated with human antibody-mediated complement-dependent cytotoxicity. COX-2 might be a potential therapeutic target to improve xenotransplantation.
- Published
- 2019
34. Transplant Tolerance: Current Insights and Strategies for Long-Term Survival of Xenografts
- Author
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Jintao Liu, Zhiwu Lv, Liu Lu, Gao Hanchao, Lisha Mou, Zhiming Cai, David K. C. Cooper, Ganlu Wang, Yifan Dai, and Chen He
- Subjects
0301 basic medicine ,Adoptive cell transfer ,T-Lymphocytes ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Immunology ,Economic shortage ,Thymus Gland ,030230 surgery ,03 medical and health sciences ,0302 clinical medicine ,Long term survival ,Immune Tolerance ,medicine ,Animals ,Humans ,Immunology and Allergy ,Immunologic Tolerance ,Transplantation Chimera ,Mixed chimerism ,business.industry ,Graft Survival ,General Medicine ,T-cell costimulation ,Transplantation ,030104 developmental biology ,Heterografts ,Transplantation Tolerance ,business - Abstract
Xenotransplantation is an attractive solution to the problem of allograft shortage. However, transplants across discordant species barriers are subject to vigorous immunologic and pathobiologic hurdles, some of which might be overcome with the induction of immunologic tolerance. Several strategies have been designed to induce tolerance to a xenograft at both the central (including induction of mixed chimerism and thymic transplantation) and peripheral (including adoptive transfer of regulatory cells and blocking T cell costimulation) levels. Currently, xenograft tolerance has been well-established in rodent models, but these protocols have not yet achieved similar success in nonhuman primates. This review will discuss the major barriers that impede the establishment of immunological tolerance across xenogeneic barriers and the potential solution to these challenges, and provide a perspective on the future of the development of novel tolerance-inducing strategies.
- Published
- 2018
35. HDAC Inhibitors: Novel Immunosuppressants for Allo- and Xeno- Transplantation
- Author
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Yifan Dai, Zhang Qing, Lisha Mou, and Zhiming Cai
- Subjects
0301 basic medicine ,Transplantation ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,General Chemistry ,business ,Organ transplantation - Published
- 2018
36. Drug repurposing: Ibrutinib exhibits immunosuppressive potential in organ transplantation
- Author
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Cuibing Zhou, Zhang Qing, Yang Li, Song Zhang, Zhiming Cai, Zhao Chengjiang, Chen Jicheng, Chengjun Wang, Gao Hanchao, and Lisha Mou
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Swine ,Immune rejection ,CD3 ,medicine.medical_treatment ,T cell ,Transplants ,Xeno-transplantation ,Pharmacology ,Allo-transplantation ,Organ transplantation ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Piperidines ,medicine ,Animals ,Transplantation, Homologous ,Immunosuppressant ,Mice, Inbred BALB C ,biology ,business.industry ,Adenine ,Ibrutinib ,Drug Repositioning ,General Medicine ,medicine.disease ,Mice, Inbred C57BL ,Transplantation ,Pyrimidines ,030104 developmental biology ,Graft-versus-host disease ,Cytokine ,medicine.anatomical_structure ,chemistry ,Leukocytes, Mononuclear ,biology.protein ,Pyrazoles ,Female ,business ,Immunosuppressive Agents ,Ex vivo ,Research Paper - Abstract
Long-term administration of classic immunosuppressants can induce severe adverse effects. The development of novel immunosuppressants confronts great challenges and opportunities. Ibrutinib, an approved drug for B-cell lineages and chronic graft versus host disease (cGVHD), exhibits immunosuppressive efficacy in autoimmune diseases. Ibrutinib's potential as an immunosuppressant in organ transplantation has not been investigated to date. In a xeno-artery patch model ex vivo, ibrutinib inhibited the proliferation of PBMCs (POD 14-42), mainly CD3+CD4+ and CD3+CD8+ T cells ex vivo. The secretion of cytokines (IL-6, IL-2 and IFN-γ) was suppressed in response to ibrutinib. In allo-skin transplantation models, ibrutinib delayed the rejection of grafted skins. Ibrutinib decreased the amount of T/B cells and lymphocyte infiltration. Altogether, ibrutinib exhibited immunosuppressive potential through cytokine regulation and T cell inhibition ex vivo and in vitro. Repositioning of ibrutinib as an immunosuppressant will greatly facilitate novel immunosuppressant development.
- Published
- 2018
37. MVDRNet: Multi-view diabetic retinopathy detection by combining DCNNs and attention mechanisms
- Author
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Yong Xu, Jiying Hu, Luo Xiaoling, Zuhui Pu, Baikang Ye, Lisha Mou, Xiaoyan Dou, Wai Keung Wong, and Jingyong Su
- Subjects
Computer science ,business.industry ,Deep learning ,Feature extraction ,Pattern recognition ,02 engineering and technology ,Diabetic retinopathy ,Fundus (eye) ,medicine.disease ,01 natural sciences ,Artificial Intelligence ,0103 physical sciences ,Signal Processing ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,020201 artificial intelligence & image processing ,Computer Vision and Pattern Recognition ,Artificial intelligence ,010306 general physics ,business ,Software - Abstract
Diabetic retinopathy (DR) detection has attracted much attention recently, and the deep learning algorithms have gained traction in this area. At present, DR screening by deep learning algorithms is often based on single-view fundus images, which usually leads to an unsatisfactory accuracy of DR grading due to the incomplete lesion features. In this paper, we proposed a novel diabetic retinopathy detection convolutional network for automatic DR detection by integrating multi-view fundus images. Compared to existing single-view DCNN-based DR detection methods, the proposed method has the following advantages. First, our method fully utilizes the lesion features from the retina with a field-of-view around 120 ∘ − 150 ∘ . Second, by introducing the attention mechanisms, more attention will be paid on the influential view and the performance can be improved. Besides, we also assign large weights to important channels in the network for effective feature extraction. Experiments are conducted on our collected multi-view DR dataset contained 15,468 images, in which each eye sample provides four-view images. The experimental results indicate that using multi-view images is suitable for automatic DR detection and our proposed method is superior to other benchmarking methods.
- Published
- 2021
38. R383C mutation of human CDC20 results in idiopathic non-obstructive azoospermia
- Author
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Nanni Peng, Liqing Fan, Weiren Huang, Lisha Mou, Lingwei Li, and Lihua Yang
- Subjects
0301 basic medicine ,Azoospermia ,Cyclin-dependent kinase 1 ,030219 obstetrics & reproductive medicine ,Idiopathic azoospermia (IA) ,biology ,Cyclin-dependent kinase 2 ,Cyclin B ,CDC20 ,Cell cycle ,medicine.disease ,CDC20 R383C mutant ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Securin ,Immunology ,Cancer research ,medicine ,biology.protein ,Missense mutation ,Research Paper - Abstract
Idiopathic azoospermia (IA) is a severe form of male infertility due to unknown causes. To investigate relative gene expression in human idiopathic non-obstructive azoospermia, we sequenced all the exons of cell division cycle 20 (CDC20) in 766 patients diagnosed with IA, as well as in 521 normally fertile men. Three novel missense mutations (S72G, R322Q, R383C) of CDC20 were detected and further confirmed by Sanger sequencing. The mRNA levels of securin, cyclin B, cyclin dependent kinase 1 (CDK1), and cyclin dependent kinase 2 (CDK2), which are all targeted for destruction via the anaphase-promoting complex/cyclosomeCDC20 (APC/CCDC20) pathway, were detected at relatively high levels using real-time quantitative polymerase chain reaction analysis. This demonstrated that the CDC20 R383C mutation led to dysfunction during the transition from metaphase to anaphase and facilitation of mitotic exit in vitro, and caused prolonged mitotic arrest during the cell cycle. This study suggests that a CDC20 R383C mutation may result in the pathogenesis of human IA.
- Published
- 2017
39. CCR6 is required for ligand-induced CatSper activation in human sperm
- Author
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Tao Wang, Yan Wang, Ye Chun Ruan, Xiaofeng Li, Ruiying Diao, Hsiao Chang Chan, Lisha Mou, Kin Lam Fok, Hao Chen, Xuhui Zeng, Mei Kuen Yu, Chen Ying, Zhiming Cai, Xueyong Cai, and Yimin Cheng
- Subjects
0301 basic medicine ,Traditional medicine ,Hyperactivation ,urogenital system ,Acrosome reaction ,chemical and pharmacologic phenomena ,hemic and immune systems ,C-C chemokine receptor type 6 ,human β-defensin-1 ,progesterone ,Biology ,sperm ,Sperm ,Andrology ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Cytosolic ca ,CatSper ,Male fertility ,CATSPER channel ,CCR6 ,Sperm motility ,Research Paper - Abstract
// Ruiying Diao 1, * , Tao Wang 2, * , Kin Lam Fok 3, * , Xiaofeng Li 3 , Yechun Ruan 3, 4 , Mei Kuen Yu 3 , Yimin Cheng 2 , Ying Chen 2 , Hao Chen 1, 3 , Lisha Mou 1 , Xueyong Cai 1 , Yan Wang 3 , Zhiming Cai 1 , Xuhui Zeng 2 and Hsiao Chang Chan 3, 5 1 Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China 2 Institute of Life Science and School of Life Science, Nanchang University, Nanchang, China 3 Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China 4 Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China 5 Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China * These authors have contributed equally to this work Correspondence to: Hsiao Chang Chan, email: hsiaocchan@cuhk.edu.hk Xuhui Zeng, email: xuhuizeng@hotmail.com Zhiming Cai, email: caizhiming2000@163.com Keywords: CCR6, CatSper, human β-defensin-1, progesterone, sperm Received: May 26, 2017 Accepted: July 13, 2017 Published: September 05, 2017 ABSTRACT CatSper channel has been considered the principal sperm Ca 2+ channel responsible for the cytosolic Ca 2+ elevation required for various sperm functions necessary for fertilization [ 1 – 4 ]. However, the mechanism underlying the activation of CatSper channel by various physiological ligands remain incompletely understood. We have recently demonstrated the expression of C-C chemokine receptor 6 (CCR6) in sperm and Ca 2+ influx upon binding of human β-defensin 1 (DEFB1) to CCR6, which is important for sperm motility [ 5 ]. In the present study, we have demonstrated that CCR6 receptor and CatSper channel are both required for the Ca 2+ entry/current induced by physiological ligands DEFB1, chemokine (C-C motif) ligand 20 (CCL20) and progesterone in human sperm. CCR6 is co-localized and interacts with CatSper in human sperm. Ca 2+ influx mediated by CCR6 and CatSper is required for essential sperm functions, including motility, hyperactivation and acrosome reaction, which are impaired in infertile sperm showing reduced levels of CCR6 and CatSper. The present finding suggests a critical role of CCR6 receptor in mediating ligand-induced, CatSper-dependent Ca 2+ influx required for various sperm functions and thus male fertility.
- Published
- 2017
40. Pig-to-Primate Islet Xenotransplantation: Past, Present, and Future
- Author
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Lisha Mou, Zhiming Cai, Hu Wenbao, David K. C. Cooper, Rita Bottino, Hidetaka Hara, Tian He, Yifan Dai, and Liu Zhengzhao
- Subjects
Graft Rejection ,Primates ,0301 basic medicine ,endocrine system ,endocrine system diseases ,Swine ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Islets of Langerhans Transplantation ,Biomedical Engineering ,lcsh:Medicine ,Review ,030230 surgery ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Diabetes mellitus ,medicine ,Animals ,Transplantation ,geography ,Type 1 diabetes ,geography.geographical_feature_category ,Graft rejection ,business.industry ,lcsh:R ,Cell Biology ,Islet ,medicine.disease ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,Immunology ,business ,Allotransplantation - Abstract
Islet allotransplantation results in increasing success in treating type 1 diabetes, but the shortage of deceased human donor pancreata limits progress. Islet xenotransplantation, using pigs as a source of islets, is a promising approach to overcome this limitation. The greatest obstacle is the primate immune/inflammatory response to the porcine (pig) islets, which may take the form of rapid early graft rejection (the instant blood-mediated inflammatory reaction) or T-cell-mediated rejection. These problems are being resolved by the genetic engineering of the source pigs combined with improved immunosuppressive therapy. The results of pig-to-diabetic nonhuman primate islet xenotransplantation are steadily improving, with insulin independence being achieved for periods >1 year. An alternative approach is to isolate islets within a micro- or macroencapsulation device aimed at protecting them from the human recipient's immune response. Clinical trials using this approach are currently underway. This review focuses on the major aspects of pig-to-primate islet xenotransplantation and its potential for treatment of type 1 diabetes.
- Published
- 2017
41. Altered expression of eNOS, prostacyclin synthase, prostaglandin G/H synthase, and thromboxane synthase in porcine aortic endothelial cells after exposure to human serum-relevance to xenotransplantation
- Author
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Zhaoming Liu, Huirong Nie, Zhiming Cai, Yu Zhao, David K. C. Cooper, Liangxue Lai, Qingjian Zou, Ying Lu, Yifan Dai, Chen Pengfei, Aifa Tang, Nana Fan, Gao Hanchao, Hidetaka Hara, and Lisha Mou
- Subjects
0301 basic medicine ,medicine.medical_specialty ,biology ,Prostaglandin ,Cell Biology ,General Medicine ,biology.organism_classification ,Prostacyclin synthase ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Endocrinology ,chemistry ,Enos ,Internal medicine ,Hemostasis ,cardiovascular system ,medicine ,biology.protein ,Platelet ,Platelet activation ,Thromboxane-A synthase - Abstract
Under normal conditions, the activity of platelets is stringently and precisely balanced between activation and quiescent state. This guarantees rapid hemostasis and avoids uncontrolled thrombosis. However, excessive platelet activation and resulting thrombotic microangiopathy are frequently observed in pig-to-primate xenotransplantation models. Endothelium-derived inhibitory mechanisms play an important role in regulation of platelet activation. These mainly include nitric oxide (NO), prostacyclin PGI2 , and adenosine, which are synthesized by endothelial NO synthases (eNOS), prostacyclin synthase, and CD39/CD73, respectively. We investigated whether endothelium-derived regulatory mechanisms are affected in porcine aortic endothelial cells (PAECs) after exposure to human serum. In the present study, exposure of PAECs or porcine iliac arteries to human serum suppressed gene expression of eNOS and prostacyclin synthase, while induced gene expression of prostaglandin G/H synthase and thromboxane synthase. Simultaneously, exposure to human serum reduced NO and PGI2 production in PAEC culture supernatants. Thus, human serum altered the balance of endothelium-derived inhibitory mechanisms in PAECs, which may indicate a regulatory mechanism of excessive platelet activation in pig-to-primate xenotransplantation.
- Published
- 2017
42. A nurse‐coordinated model of care versus usual care for chronic kidney disease: meta‐analysis
- Author
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Zhiming Cai, RN Haidan Xu Bsn, and Lisha Mou
- Subjects
medicine.medical_specialty ,Myocardial Infarction ,030232 urology & nephrology ,Nursing assessment ,Renal function ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Ambulatory care ,Risk Factors ,Humans ,Medicine ,Models, Nursing ,030212 general & internal medicine ,Intensive care medicine ,General Nursing ,Randomized Controlled Trials as Topic ,Heart Failure ,Practice Patterns, Nurses' ,business.industry ,Disease Management ,General Medicine ,medicine.disease ,Clinical trial ,Meta-analysis ,Heart failure ,Disease Progression ,Quality of Life ,Kidney Failure, Chronic ,business ,Kidney disease - Abstract
Aim To investigate whether a nurse-led care was more beneficial for implementing chronic kidney disease guidelines and improved multiple risk factors compared with the usual care. Background Several independent clinical trials have been carried out to demonstrate the efficiency of a nurse-led care to improve the outcomes for patients with chronic kidney disease and address the risk factors for renal function decline. However, their results and conclusions were inconsistent. Methods A meta-analysis was carried out on September 2015 based on previous studies that evaluated the efficiency of nurse-led care model for patients with chronic kidney disease. Following quality appraisal, four randomised clinical trials that allocated patients with chronic kidney disease to usual care and nurse-coordinated care were included. Primary outcomes, such as kidney failure and cardiovascular events, were analysed. Results Compared with the usual care group, a nurse-coordinated care model reduced the risks of composite death, decreased the occurrence rate of end-stage renal disease and doubled serum creatinine. On the contrary, a slight propulsive effect of nurse-led interventional care occurred on acute myocardial infarction and heart failure. Limitations Only five studies were included and conducted nonstandard evaluating endpoints, causing fewer studies were categorised in each outcome events in this meta-analysis, subsequently leading to heterogeneity and less persuasive. Conclusions Intensive interventions delivered by nurse coordinators are expected to benefit patients to attain longer life expectancy and higher life quality as well as to improve controlling risk factors implicated in chronic kidney disease progression. Relevance to clinical practice More government and hospitals should modify the traditional nursing routine based on this study, providing a more intensive nurse-coaching care model for patients with chronic kidney disease, even aged or other chronic diseases, which shall further help to better control the risk factors and delay disease progression.
- Published
- 2017
43. Male infertility-related molecules involved in sperm-oocyte fusion
- Author
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Ni Xie and Lisha Mou
- Subjects
Male ,0301 basic medicine ,Infertility ,endocrine system ,Immunoglobulins ,Cell Communication ,Review ,Biology ,Bioinformatics ,medicine.disease_cause ,Membrane Fusion ,Permeability ,Male infertility ,Mice ,IZUMO1 ,03 medical and health sciences ,Human reproduction ,Human fertilization ,medicine ,Animals ,Humans ,Infertility, Male ,reproductive and urinary physiology ,Sperm-Ovum Interactions ,Mutation ,urogenital system ,Mechanism (biology) ,Membrane Proteins ,Anatomy ,Sperm-oocyte fusion ,Oocyte ,medicine.disease ,Spermatozoa ,Sperm ,Chromatin ,Anti-Bacterial Agents ,Bactericidal/permeability-increasing protein (BPI) ,030104 developmental biology ,medicine.anatomical_structure ,Fertilization ,Oocytes ,Female ,Animal Science and Zoology - Abstract
Male infertility has become a very serious problem in the human reproduction system, but the molecular mechanism of infertility remains largely unknown. Fertilization is the phenomenon in which a sperm and oocyte find each other, interact, and fuse. Sperm-oocyte fusion-related factors on the sperm side play crucial roles in male infertility. For example, IZUMO1 is well-known as a sperm protein essential for fusion of a sperm and oocyte, but its dysfunction or mutation can result in male infertility. Recent studies showed a novel sperm protein named Bactericidal/permeability-increasing protein (BPI), which takes part in the sperm-oocyte fusion process. The complexity and expected redundancy of the factors involved makes the process intricate, with a still poorly understood mechanism, which is difficult to comprehend in full detail. This review summarizes the known molecules involved in the process of sperm-oocyte fusion, mainly focusing on the relevant factors on the sperm side, whose dysregulation may potentially be associated with male infertility. New insights may come from these molecules in this review, can facilitate the development of new treatments of male infertility, and may have a diagnostic value in infertility.
- Published
- 2017
44. A fluorescent aptasensor with product-triggered amplification by exonuclease III digestion for highly sensitive ATP detection
- Author
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Long Qu, He Shengnan, Wang Yu, Yuyang Jiang, Ying Tan, Zhiming Cai, Wei Zhang, Feng Liu, and Lisha Mou
- Subjects
Exonuclease III ,chemistry.chemical_classification ,biology ,Chemistry ,General Chemical Engineering ,Hybridization probe ,Aptamer ,Allosteric regulation ,General Engineering ,Substrate (chemistry) ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,Analytical Chemistry ,Enzyme ,Biochemistry ,biology.protein ,Nucleotide ,0210 nano-technology - Abstract
Here we proposed a conceptually new amplified ATP assay by combination of exonuclease III (Exo III) with an allosteric aptasensor triggered by ATP with graphene oxide (GO) assistance. The assay needs only one single fluorophore-labelled DNA probe, which was designed having the fluorescence labelled nucleotide and enzymatic substrate sequence away from the ATP recognition aptamer sequence to avoid the hindrance of the target recognition and enzymatic cleavage. The signal amplification mechanism is based on the binding ability of the produced dAMP to the ATP aptamer. In every cycle, the ATP can trigger the assay probe to be digested by the Exo III. The digestion product includes 3 dAMPs, which also can trigger the assay probe. The limit of detection as low as 31 nM was achieved, which is very competitive compared to those of other aptasensors with a signal amplification strategy for ATP detection. We envision that this principle could facilitate the design and development of other aptamer-based ATP sensors using different nucleases and find their potential applications in biological and environmental fields in the future.
- Published
- 2017
45. Production of α1,3-galactosyltransferase and cytidine monophosphate-N-acetylneuraminic acid hydroxylase gene double-deficient pigs by CRISPR/Cas9 and handmade cloning
- Author
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Dengke Pan, Xi Xiang, Yong Li, Zhao Chengjiang, David K. C. Cooper, Yifan Dai, Zhiming Cai, Yanli Zhao, Hidetaka Hara, Lisha Mou, Gao Hanchao, and Zesong Li
- Subjects
0301 basic medicine ,Nuclear Transfer Techniques ,Genotype ,Swine ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Cell ,030230 surgery ,Biology ,Antibodies ,Mixed Function Oxygenases ,Animals, Genetically Modified ,Gene Knockout Techniques ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Handmade cloning ,Animals ,CRISPR ,Cloning, Molecular ,CRISPR/Cas9 ,Gene ,Alleles ,Cloning ,Cumulus Cells ,Cas9 ,Cytidine ,Fibroblasts ,Galactosyltransferases ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,Animals, Newborn ,chemistry ,Double-knockout pigs ,Immunoglobulin G ,Leukocytes, Mononuclear ,Oocytes ,Somatic cell nuclear transfer ,Original Article ,Animal Science and Zoology ,CRISPR-Cas Systems - Abstract
Gene-knockout pigs hold great promise as a solution to the shortage of organs from donor animals for xenotransplantation. Several groups have generated gene-knockout pigs via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) and somatic cell nuclear transfer (SCNT). Herein, we adopted a simple and micromanipulator-free method, handmade cloning (HMC) instead of SCNT, to generate double gene-knockout pigs. First, we applied the CRISPR/Cas9 system to target α1,3-galactosyltransferase (GGTA1) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes simultaneously in porcine fetal fibroblast cells (PFFs), which were derived from wild-type Chinese domestic miniature Wuzhishan pigs. Cell colonies were obtained by screening and were identified by Surveyor assay and sequencing. Next, we chose the GGTA1/CMAH double-knockout (DKO) cells for HMC to produce piglets. As a result, we obtained 11 live bi-allelic GGTA1/CMAH DKO piglets with the identical phenotype. Compared to cells from GGTA1-knockout pigs, human antibody binding and antibody-mediated complement-dependent cytotoxicity were significantly reduced in cells from GGTA1/CMAH DKO pigs, which demonstrated that our pigs would exhibit reduced humoral rejection in xenotransplantation. These data suggested that the combination of CRISPR/Cas9 and HMC technology provided an efficient and new strategy for producing pigs with multiple genetic modifications.
- Published
- 2017
46. A green tea–triggered genetic control system for treating diabetes in mice and monkeys
- Author
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Jianli Yin, Kaili Dong, Lisha Mou, Ying Xu, Linfeng Yang, Haifeng Ye, Jian Jiang, Xinyi Wang, Ying Lu, and Shuai Xue
- Subjects
Male ,Placenta ,Transgene ,Administration, Oral ,Computational biology ,Mice ,Synthetic biology ,Genome editing ,Pregnancy ,Hydroxybenzoates ,Animals ,Humans ,Epigenetics ,Gene ,Tea ,biology ,Streptomyces coelicolor ,HEK 293 cells ,Translation (biology) ,Haplorhini ,General Medicine ,biology.organism_classification ,Diabetes Mellitus, Type 1 ,HEK293 Cells ,Diabetes Mellitus, Type 2 ,Female ,Synthetic Biology - Abstract
Cell-based therapies are recognized as the next frontier in medicine, but the translation of many promising technologies into the clinic is currently limited by a lack of remote-control inducers that are safe and can be tightly regulated. Here, we developed therapeutically active engineered cells regulated by a control system that is responsive to protocatechuic acid (PCA), a metabolite found in green tea. We constructed multiple genetic control technologies that could toggle a PCA-responsive ON/OFF switch based on a transcriptional repressor from Streptomyces coelicolor We demonstrated that PCA-controlled switches can be used for guide RNA expression-mediated control of the CRISPR-Cas9 systems for gene editing and epigenetic remodeling. We showed how these technologies could be used as implantable biocomputers in live mice to perform complex logic computations that integrated signals from multiple food metabolites. Last, we used our system to treat type 1 and type 2 diabetes in mice and cynomolgus monkeys. This biocompatible and versatile food phenolic acid-controlled transgenic device opens opportunities for dynamic interventions in gene- and cell-based precision medicine.
- Published
- 2019
47. PNet: An Efficient Network for Pneumonia Detection
- Author
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Yingqi Li, Lisha Mou, Juan Yu, Zhongliang Li, Linlin Shen, Xuechen Li, Wei-cai Dai, and Zuhui Pu
- Subjects
medicine.medical_specialty ,Lung ,020205 medical informatics ,medicine.diagnostic_test ,business.industry ,Deep learning ,CAD ,Physical examination ,02 engineering and technology ,medicine.disease ,Convolutional neural network ,Pneumonia ,medicine.anatomical_structure ,Radiological weapon ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,020201 artificial intelligence & image processing ,Radiology ,Artificial intelligence ,F1 score ,business - Abstract
Pneumonia is a common lung disease and affects millions of people worldwide each year. The chest X-ray is one of the most commonly accessible radiological examinations for screening and diagnosing lung diseases. Usually, chest X-ray images (CXRs) are taken at physical examination and evaluated by radiologists. The unbalance between tremendous numbers of CXRs and limited number of radiologists need to be solved by Computer Assisted Diagnosis (CAD). As deep neural networks have shown promising results in CAD, we implemented a deep learning-based framework, PNet, for pneumonia detection. 10784 chest X-ray images collected at the Shenzhen No.2 People's Hospital were employed for training and evaluation. The experimental results showed that the proposed PNet (1,695,777 parameters) achieved higher accuracy and F1 score than classical networks like AlexNet (42,725,889 parameters) and VGG16 (27,560,769 parameters).
- Published
- 2019
48. hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs
- Author
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Xiao‑Li Zeng, Xue‑Song Deng, Bo Qin, Zi‑Gang Huang, Ying Lu, Lisha Mou, Ming Zhou, and Chun‑Chen Wu
- Subjects
0301 basic medicine ,Cancer Research ,Organic anion transporter 1 ,Swine ,Gene Expression ,medicine.disease_cause ,Biochemistry ,Mice ,0302 clinical medicine ,Cells, Cultured ,media_common ,Symporters ,virus diseases ,Articles ,Hepatitis B ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Lentivirus ,Molecular Medicine ,Rabbits ,Drug ,Hepatitis B virus ,media_common.quotation_subject ,Organic Anion Transporters, Sodium-Dependent ,Microbial Sensitivity Tests ,Biology ,Antiviral Agents ,03 medical and health sciences ,Species Specificity ,Viral entry ,Genetics ,medicine ,Animals ,Humans ,primary pig hepatocyte ,Molecular Biology ,cell model ,medicine.disease ,biology.organism_classification ,Virology ,digestive system diseases ,Rats ,030104 developmental biology ,Apoptosis ,Hepatocytes ,biology.protein ,sodium taurocholate co-transporting polypeptide - Abstract
Primary human hepatocytes (PHHs) are the 'gold standard' for investigating hepatitis B virus (HBV) infection and antiviral drugs. However, poor availability, variation between batches and ethical issues regarding PHHs limit their applications. The discovery of human sodium taurocholate co‑transporting polypeptide (hNTCP) as a functional HBV receptor has enabled the development of a surrogate model to supplement the use of PHHs. In the present study, the evolutionary distance of seven species was assessed based on single‑copy homologous genes. Based on the evolutionary distance and availability, PHHs and primary rabbit hepatocytes (PRHs) were isolated and infected with hNTCP‑recombinant lentivirus, and susceptibility to HBV infection in the two cell types was tested and compared. In addition, HBV infection efficiency of hNTCP‑expressing PPHs with pooled HBV‑positive serum and purified particles was determined. The potential use of HBV‑infected hNTCP‑expressing PPHs for drug screening was assessed. The results demonstrated that pigs and rabbits are closer to humans in the divergence tree compared with mice and rats, indicating that pigs and rabbits were more likely to facilitate the HBV post‑entry lifecycle. Following hNTCP complementation and HBV infection, PPHs and Huh7D human hepatocellular carcinoma cells, but not PRHs, exhibited increased hepatitis B surface antigen and hepatitis B e‑antigen secretion, covalently closed circular DNA formation and infectious particle secretion. hNTCP‑expressing PPHs were susceptible to infection with HBV particles purified from pooled HBV‑positive sera, but were poisoned by raw HBV‑positive sera. The use of HBV‑infected hNTCP‑expressing PPHs for viral entry inhibitor screening was revealed to be applicable and reproducible. In conclusion, hNTCP‑expressing PPHs may be valuable tool for investigating HBV infection and antiviral drugs.
- Published
- 2019
49. Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells
- Author
-
Junfang Zhang, Lisha Mou, Zepeng Qu, Dengke Pan, David K. C. Cooper, Yifan Dai, Wang Xiliang, Ming Zhou, Chongwei Xie, Wenjie Dai, Hidetaka Hara, and Zhiming Cai
- Subjects
Transplantation ,Gene knockdown ,Swine ,Immunogenicity ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Immunology ,Endothelial Cells ,Biology ,medicine.disease_cause ,Molecular biology ,Animals, Genetically Modified ,Gene Knockout Techniques ,Immune system ,Downregulation and upregulation ,Antigen ,Antigens, Heterophile ,medicine ,Animals ,Heterografts ,Carcinogenesis ,Cytotoxicity ,Microtubule-Associated Proteins ,Adaptor Proteins, Signal Transducing - Abstract
After hyperacute rejection in pig-to-primate xenotransplantation had been overcome by the introduction of α1,3-galactosyltransferase gene-knockout (GTKO) pigs, acute and chronic antibody-mediated rejection became one of the major barriers to long-term graft survival. This was associated with exposure of non-Gal antigens to the recipient's immune system and indicated that further genetic engineering of the pigs would be necessary. We here report that Gabarapl1, a regulator of tumorigenesis, plays a role in the regulation of immunogenicity of porcine aortic endothelial cells (PAECs). Knockdown of Gabarapl1 in PAECs results in a remarkable reduction in binding of serum antibody from PAEC-immunized monkeys, associated with decreased serum cytotoxicity of pig cells. Expression of swine leukocyte antigens (SLA) II DR was downregulated by Gabarapl1 knockdown. However, suppression of expression of SLA II is associated with less reduction of antibody binding than achieved by Gabarapl1 knockdown, suggesting that other Gabarapl1-regulated xenoantigens may be more important. These findings indicate a hitherto unknown relationship between Gabarapl1 and xenoimmunogenicity, suggesting a potential new strategy to reduce rejection initiated by the presence of non-Gal antigens.
- Published
- 2019
50. A potential role of TLR2 in xenograft rejection of porcine iliac endothelial cells: An in vitro study
- Author
-
Zepeng Qu, Chen Jicheng, LinLin Chen, Lisha Mou, Gao Hanchao, Zhiming Cai, Xisheng Wang, David K. C. Cooper, and Zongpei Song
- Subjects
Graft Rejection ,0301 basic medicine ,Chemokine ,Swine ,Xenotransplantation ,medicine.medical_treatment ,Blotting, Western ,Transplantation, Heterologous ,Immunology ,Enzyme-Linked Immunosorbent Assay ,In Vitro Techniques ,030230 surgery ,Real-Time Polymerase Chain Reaction ,Iliac Artery ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Interleukin 8 ,Antibody-dependent cell-mediated cytotoxicity ,Transplantation ,biology ,Chemistry ,Endothelial Cells ,Chemotaxis ,Acquired immune system ,Toll-Like Receptor 2 ,TLR2 ,030104 developmental biology ,biology.protein ,Cancer research ,Biomarkers - Abstract
BACKGROUND Porcine vascular endothelial cells are a major participant in xenograft rejection. The Toll-like receptor 2 (TLR2) pathway plays an important role in both innate and adaptive immunity. The specific role of TLR2 in the response to a xenograft has not been reported. Whether the TLR2 pathway in pig vascular endothelial cells is involved in acute rejection needs to be investigated, and the mechanism is explored. METHODS We used a modified antibody-dependent complement-mediated cytotoxicity (ADCC) assay to conduct in vitro experiments. In porcine iliac artery endothelial cells (PIECs), siRNA was used to knock down the expression of TLR2, CXCL8, and CCL2. The effect of human serum or inactivated human serum on the expression of TLR2 was analyzed by real-time PCR and Western blotting, and transwell assays were used to assess the chemotactic efficiency of PIECs on human monocyte-macrophages (THP-1 cells) and human neutrophils. The downstream signaling pathways activated by human serum were detected by Western blotting, and the regulation of proinflammatory chemokines and cytokines by TLR2 signaling was assessed by real-time PCR and ELISA. RESULTS TLR2 was significantly upregulated in PIECs after exposure to human serum, and porcine proinflammatory chemokines, CXCL8 and CCL2, were induced, at least partially, in a TLR2-dependent pattern; the upregulated chemokines participated in the chemotaxis of human neutrophils and THP-1 cells across the species barrier. CONCLUSIONS (i) TLR2 is significantly upregulated in PIECs by human serum, (ii) the elevated TLR2 participates in the chemotaxis of inflammatory cells through the secretion of chemokine CCL2 and CXCL8, and (iii) blockade of TLR2 would be beneficial for xenograft survival.
- Published
- 2019
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