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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng zhang Xiaodan zhang shuijun zhang Wenzhi Guo Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Diagnosis&Treatment League for Hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Innovative Research Group for Hepatobiliary&Pancreatic Surgery and Digestive Organ Transplantation Zhengzhou 450052China Henan Organ Transplantation Quality Control Centre Zhengzhou 450052China Henan Engineering Technology Research Center for Organ Transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis Institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

The Effect of FOXP3^(+) Regulatory T Cells on Infectious and Inflammatory Diseases

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Infectious Microbes & Diseases 2021年第4期3卷 187-197页

作者： Yakun Bai Fang Gao Dan Li Suyuan Ji shuijun zhang Wenzhi Guo Bin Li Zhengzhou Engineering Laboratory of Organ Transplantation Technique and Application ZhengzhouHenanChina Henan Engineering Technology Research Center of Organ Transplantation ZhengzhouHenanChina Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of ZhengzhouZhengzhouHenanChina Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghaiChina Binzhou People’s Hospital Health Management Center BinzhouShandongChina.

CD4^(+)CD25^(+)FOXP3^(+)regulatory T cells(Tregs)contribute to the maintenance of immune homeostasis and tolerance in the *** expression levels and functional stability of FOXP3 control the function and plasticity of *** critically impact infectious diseases,especially by regulating the threshold of immune responses to pathogenic *** functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth,which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.

关键词： FOXP3 infection inflammatory disease regulatory T cells

A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes

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Protein & Cell 2014年第4期5卷 317-327页

作者： Lu Sun Yu zhang Bao Zhao Mengmeng Deng Jun Liu Xin Li Junwei Hou Mingming Gui shuijun zhang Xiaodong Li George F. Gao Songdong Meng CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences_ (CAS) Beijing 100101 China Beijing Institute of Infectious Diseases Beijing 302 Hospital Beijing 100039 China Xinjiang Agricultural University Urumqi 830052 China

Cytotoxic T cells （CTLs） play a key role in the control of Hepatitis B virus （HBV） infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein （HBc） is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool cov- ering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141- 149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti- HBV activity were further determined in HBV and HLA- A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parame- ters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.

关键词： chronic hepatitis B HLA-A2 HBc peptideCTL response antiviral cytotoxity

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation:Multicenter Propensity Score-matched Study

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 827-838页

作者： Mengfan Yang Xuyong Wei Abdul Rehman Khan Qiang Wei Rui Wang Binhua Pan Kun Wang Zhisheng Zhou Di Lu Beini Cen shuijun zhang Wenzhi Guo Shusen Zheng Yang Yang Xiao Xu Department of Organ Transplantation Qilu Hospital of Shandong UniversityJinanShandongChina Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province HangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiangChina Zhejiang University School of Medicine HangzhouZhejiangChina National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityHenanChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongChina

Background and Aims:Liver transplantation(LT)using ABO-incompatible(ABOi)grafts can extend the donor pool to a certain extent and hence reduce the waiting time for ***,concerns of the impending prognosis associated with this option,especially for patients with liver failure and higher model for end-stage liver disease(MELD)scores,who tend to be more fragile during the waiting period before ***:Recipients undergoing LT for acute-onchronic liver failure or acute liver failure were retrospectively enrolled at four *** survival was compared and a Cox regression analysis was *** score matching was performed for further *** were stratified by MELD score and cold ischemia time(CIT)to determine the subgroups with survival ***:Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible(ABOc)LT were *** 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching(50.6%vs.75.7%,p0.05).Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores≥40(p>0.05).For patients with MELD scores of 31-39,the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group(p<0.001);however,the rate was increased when the liver graft CIT was<8 ***:For recipients with MELD scores≤30,ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible *** recipients with MELD scores≥40,ABOi should be adopted with caution in emergency *** recipients with MELD scores of 31-39,the ABOi LT prognosis was ***,those patients benefited from receiving ABOi grafts with a CIT of<8 h.

关键词： Liver transplantation ABO-incompatible Model for end-stage liver disease score Cold ischemia time Propensity score matching

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死亡后器官捐献供者器官的质量评估与保护

中华器官移植杂志 2018年第11期39卷 643-644页

作者：张水军郑州大学第一附属医院肝胆胰外科河南省消化器官移植重点实验室郑州市肝胆胰疾病与器官移植医学重点实验室河南省高等学校肝胆胰外科与消化器官移植重点学科开放实验450052

目前,死亡后器官捐献(Deceased ***)即公民逝世后器官捐献(Donation after citizen'sdeath,DCD),已成为我国器官移植供者器官的主要来源。然而捐献的器官本身可能存在病变,及DD供者发生脑死亡或心脏停搏后出现一系列的病理生理变化,会... 详细信息

目前,死亡后器官捐献(Deceased ***)即公民逝世后器官捐献(Donation after citizen'sdeath,DCD),已成为我国器官移植供者器官的主要来源。然而捐献的器官本身可能存在病变,及DD供者发生脑死亡或心脏停搏后出现一系列的病理生理变化,会导致或加重供者器官功能损伤[1]。

关键词：器官捐献脑死亡供者质量评估保护病理生理变化器官功能损伤器官移植

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重视术前合并症对器官移植的影响

中华器官移植杂志 2020年第8期41卷 449-450页

作者：张水军郑州大学第一附属医院肝胆胰外科河南省器官移植中心河南省肝移植中心郑州450052

器官移植已经成为治疗终末期器官疾病的有效方法,然而越来越多的器官移植受者移植前合并其他系统疾病,如不及时处理会影响器官移植疗效。结合国内外器官移植中心数据,分析合并症对器官移植的影响,增强对器官移植过程中合并症的认识,为... 详细信息

器官移植已经成为治疗终末期器官疾病的有效方法,然而越来越多的器官移植受者移植前合并其他系统疾病,如不及时处理会影响器官移植疗效。结合国内外器官移植中心数据,分析合并症对器官移植的影响,增强对器官移植过程中合并症的认识,为移植物长期生存提供保障。

关键词：器官移植合并症移植疗效

程序性细胞死亡在肝脏缺血-再灌注损伤中的作用研究进展

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器官移植 2022年第5期13卷 647-652页

作者：白杨史冀华张水军郑州大学第一附属医院肝胆胰外科郑州450052

肝移植是治疗终末期肝病的有效手段,但在肝移植过程中不可避免会发生肝脏缺血-再灌注损伤(HIRI),可能导致早期移植物功能障碍或加剧排斥反应,其损伤防护机制有待深入研究。程序性细胞死亡是HIRI的重要发生机制,多种新型程序性细胞死亡... 详细信息

肝移植是治疗终末期肝病的有效手段,但在肝移植过程中不可避免会发生肝脏缺血-再灌注损伤(HIRI),可能导致早期移植物功能障碍或加剧排斥反应,其损伤防护机制有待深入研究。程序性细胞死亡是HIRI的重要发生机制,多种新型程序性细胞死亡形式参与了HIRI的病理过程,深入研究程序性细胞死亡有望进一步提高肝移植的治疗效果。本文就细胞凋亡、自噬及自噬依赖性死亡、铁死亡、坏死性凋亡、细胞焦亡、多聚二磷酸腺苷核糖聚合酶(PARP)-1依赖性细胞死亡等常见的程序性细胞死亡方式在HIRI中的研究进展予以综述,以期为提高肝移植手术成功率、改善受者预后提供参考。

关键词：肝移植肝脏缺血-再灌注损伤(HIRI) 程序性细胞死亡细胞凋亡自噬铁死亡坏死性凋亡细胞焦亡多聚二磷酸腺苷核糖聚合酶-1依赖性细胞死亡

Panel-reactive antibody levels and renal transplantation rates in sensitized patients after desensitization and human leucocyte antigen amino acid residue matching

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Panel-reactive antibody levels and renal transplantation rat...

Competition of cell adhesion and immune recognition:insights into the interaction between CRTAM and Nectin-like 2

2013中国器官移植大会

作者： Wenjun Shang Guiwen Feng Xinlu Pang Jinfeng Li Lei Liu Yonghua Feng Hongchang Xie shuijun zhang 郑州大学第一附属医院肾移植科

To determine whether a new desensitization protocol(mycophenolate mofetil[MMF],plasmapheresis and antithymocyte globulin [ATG],complemented with human leucocyte antigen[HLA]amino acid residue matching)could reduce panel-reactive antibody(PRA) levels in sensitized patients,to facilitate successful renal transplantation. METHODS Patients awaiting transplantation with PRA levels>10%received treatment with MMF:those with PRA levels>30% were also treated with *** whose PRA level was<20%after desensitization were eligible for *** a donor became *** HLA matching and HLA amino acid residue matching were *** patients received ATG induction therapy postoperatively.

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Competition of cell adhesion and immune recognition:insights...