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Suppressing autoimmunity by TGF-β： not just through Treg cells

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Cellular & Molecular Immunology 2012年第5期9卷 371-372页

作者： Ming-Xiao he you-wen he Department of Immunology Duke University MedicalCenter Durham NC USA

Cellular ＆ Molecular Immunology （2012） 9,371-372; doi： 10.1038/cmi.2012.24; published online 13 August 2012Transforming growth factor-β （TGF-β） is a pleiotropic factor. It regulates manyaspects of T-cell biology including thymocyte development, T cell differentiation and effector T cell function.1 Previous work has shown that the loss of TGF-β signaling in the T-cell lineage leads to severe lymphopro- liferafive autoimmunity.2.3 Until now, it has been unclear to what extent the autoimmunity observed in those mice is driven by TGF- unresponsive conventional T cells, as TGF- is also crucial for the maintenance and function of regulatory T cells （Treg）. A recent study pub- lished in Nature Immunology revealed a novel role of TGF-β signaling in non-regulatory naive T cells. It was found that TGF-β controls lym- phopenia-driven T-ceU proliferation in neonatal mice, thereby preventing the development of autoimmtmity.

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Endocytosis by target cells:an essential means for perforin-and granzyme-mediated killing

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Cellular & Molecular Immunology 2012年第1期9卷 5-6页

作者： Claire Gordy you-wen he Department of Immunology Duke University Medical CenterDurhamNCUSA

D espite the critical role of cell-mediated immunity in defense against intracellular pathogens,cancer immunosurveillance and development of autoimmunity,the precise mechanisms governing the killing of target cells by cytotoxic T cells(CTLs)and natural killer(NK)cells have remained poorly *** a study published in Nature Immunology,Thiery and colleagues have for the first time visualized the movement of the cytotoxic granule proteins perforin and granzymes from the killer cell to the target cell,challenging the textbook model of granulemediated cytotoxicity and providing direct evidence for a multistep endocytosis-mediated mechanism for the entry of granzymes to the target cell’s cytoplasm.

关键词： mediated immunity killer

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

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Science China(Life Sciences) 2020年第12期63卷 1833-1849页

作者： Ligong Lu Hui Zhang Meixiao Zhan Jun Jiang Hua Yin Danielle JDauphars Shi-you Li Yong Li you-wen he Zhuhai Interventional Medical Center Zhuhai Precision Medical CenterZhuhai People's HospitalZhuhai Hospital Affiliated with Jinan UniversityZhuhai 519000China First Affiliated Hospital China Medical UniversityShenyang 110001China tricision Biotherapeutic Inc. Zhuhai 519041China Department of Immunology Duke University Medical University Medical CenterDurhamNC 27710USA

The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019(COVID-19) due to SARSCoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARSCoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

关键词： COVID-19 seroconversion neutralizing antibody spike protein SARS-CoV-2 convalescent plasma vaccine

Applications of RNA interference highthroughput screening technology in cancer biology and virology

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Protein & Cell 2014年第11期5卷 805-815页

作者： Shan Gao Chen Yang Shan Jiang Xiao-Ning Xu Xin Lu you-wen he Annie Cheung Hui Wang Department of Oncology John Radcliffe Hospital Weatherall Institute of Molecular Medicine University of Oxford Oxford OX3 9DS UK Department of Molecular Genetics and Microbiology Stony Brook University Stony Brook NY 11794 USA Department of Immunology Duke University Durham NC 27708 USA Department of Immunology Chelsea & Westminster Hospital Imperial College of London 369 Fulham Road London SW10 9NH UK Nuffield Department of Clinical Medicine Ludwig Institute for Cancer Research Oxford Branch University of Oxford Old Road Campus Research Building Oxford OX3 7DQ UK Department of Pathology Queen Mary Hospital University of Hong Kong Pokfulam Road Hong Kong China Natural Environment Research Council Centre for Ecology & Hydrology Benson Lane Wallingford Oxfordshire OX10 8BB UK Department of Zoology University of Oxford South Parks Road Oxford OX1 3PS UK

RNA interference （RNAi） is an ancient intra-cellular mechanism that regulates gene expression and cell function. Large-scale gene silencing using RNAi highthroughput screening （HTS） has opened an exciting frontier to systematically study gene function in mammalian cells. This approach enables researchers to identify gene function in a given biological context and will provide considerable novel insight. here, we review RNAi HTS strategies and applications using case studies in cancer biology and virology.

关键词： RNA interference (RNAi) short interferingRNA (siRNA) short hairpin RNA (shRNA) high-throughputscreening cancer virology

Conversion of effector CD4^(+)T cells to a CD8^(+)MHC Ⅱ-recognizing lineage

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Cellular & Molecular Immunology 2021年第1期18卷 150-161页

作者： Elizabeth Robins Ming Zheng Qingshan Ni Siqi Liu Chen Liang Baojun Zhang Jian Guo Yuan Zhuang you-wen he Ping Zhu Ying Wan Qi-Jing Li Department of Immunology Duke University Medical CenterDurhamNC 27710USA Department of Cell Biology National Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'anChina Biomedical Analysis Center Third Military Medical UniversityChongqingChina Immuno-Oncology Comprehensive Cancer CenterOhio State University Wexner Medical CenterColumbusOH 43210USA

CD4^(+)and CD8^(+)T cells are dichotomous lineages in adaptive *** conventionally viewed as distinct fates that are fixed after thymic development,accumulating evidence indicates that these two populations can exhibit significant lineage plasticity,particularly upon TCR-mediated *** define a novel CD4^(-)CD8αβ^(+)MHC Ⅱ-recognizing population generated by lineage conversion from effector CD4^(+)T ***4-CD8αβ^(+)effector T cells downregulated the expression of T helper cell-associated costimulatory molecules and inaeased the expression of cytotoxic T lymphocyte-associated cytotoxic *** shift in functional potential corresponded with a CD8^(+)-lineage skewed transcriptional ***β repertoire sequencing and in vivo genetic lineage tracing in acutely infected wild-type mice demonstrated that CD4^(-)CD8αβ^(+)effector T cells arise from fundamental lineage reprogramming of bona fide effector CD4^(+)T *** autophagy via functional deletion of the initiating kinase Vps34 or the downstream enzyme Atg7 enhanced the generation of this cell *** findings suggest that effector CD4^(+)T cells can exhibit a previously unreported degree of skewing towards the CD8^(+)T cell lineage,which may point towards a novel direction for HIV vaccine design.

关键词： CD4^(+)T cell CD8^(+)T cell ThPOK Runx3 autophagy

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C

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Journal of Pharmaceutical Analysis 2023年第6期13卷 616-624页

作者： Ping Zhu Shi-you Li Jin Ding Zhou Fei Sheng-Nan Sun Zhao-Hui Zheng Ding Wei Jun Jiang Jin-Lin Miao San-Zhong Li Xing Luo Kui Zhang Bin Wang Kun Zhang Su Pu Qian-Ting Wang Xin-Yue Zhang Gao-Liu wen Jun OLiu John Thomas August Huijie Bian Zhi-Nan Chen you-wen he Department of Clinical Immunology Xijing HospitalDepartment of Cell BiologyNational Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'an710032China Beijing Tricision Biotherapeutics Inc. Beijing100176China Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an710032China Zhuhai Tricision Biotherapuetics Inc. ZhuhaiGuangdong519040China Department of Pharmacology and Molecular Sciences Johns Hopkins University School of MedicineBaltimoreMD21205USA

Glioblastoma(GBM)is a lethal cancer with limited therapeutic *** cell(DC)-based cancer vaccines provide a promising approach for GBM *** studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor ***,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 *** patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor ***,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen *** treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC *** patient also received 28 doses of cyclophosphamide for depletion of regulatory T *** immunotherapy-related adverse events were observed during the *** antitumor CD4t and CD8t T-cell responses were *** patient remains free of disease *** is the first case report on the combination of the above three agents to treat glioblastoma *** results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

关键词： Glioblastoma multiforme DC vaccine Tumor-associated antigens Neoantigens

两种骨瓣治疗青壮年早期非创伤性股骨头坏死的中期随访结果对比

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中国矫形外科杂志 2016年第19期24卷 1760-1764页

作者：张颖刘又文何伟河南省洛阳正骨医院(河南省骨科医院) 洛阳471002 广州中医药大学广东广州510403

[目的]对不同方法治疗股骨头坏死的中期随访结果进行对比分析,以探索优势保髋方法。[方法]回顾性分析2004年7月～2009年7月本院采用缝匠肌骨瓣和旋髂深骨瓣治疗的非创伤性股骨头坏死早期患者随访的分期变化,并进行对比。[结果]两组术后... 详细信息

[目的]对不同方法治疗股骨头坏死的中期随访结果进行对比分析,以探索优势保髋方法。[方法]回顾性分析2004年7月～2009年7月本院采用缝匠肌骨瓣和旋髂深骨瓣治疗的非创伤性股骨头坏死早期患者随访的分期变化,并进行对比。[结果]两组术后X线片分析：随时间的推移两组术后坏死均有进展,且总髋数逐渐减少,需置换数量增加。术前分期与好转率和保髋率之间差异具有统计学意义,但两组好转率和保髋率组间对比差异无统计学意义,从两组统计情况来看,ⅡA期和ⅡB期保髋效果较好。两组总计酒精型坏死和激素型坏死导致的置换与特发型相比差异有统计学意义,酒精型和激素型坏死置换率高。以THA为终点,最终48个月生存率为82.47%（95%可信区间,76.35%～87.14%）,ⅡC期坏死4年生存率最低。两组生存率之间比较差异无统计学意义。[结论]缝匠肌骨瓣移植与旋髂深骨瓣移植比较,均为治疗早期股骨头坏死（ARCOⅡ期）的有效方法,两组生存率之间比较差异无统计学意义,但缝匠肌骨瓣操作简单,便于掌握,是一种值得推广可靠方法。

关键词：股骨头坏死缝匠肌骨瓣旋髂深保髋

YKL-40 as a biomarkerguide the application ofadenosine receptor A2A inhibitors for the treatment of Glioblastoma

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YKL-40 as a biomarkerguide the application ofadenosine recep...

硅胶修饰-表面分子印迹牛血红蛋白及其识别性能的研究

2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Dai Li Qiao Zhang Yuxin Zhang Zhen Wang you-wen he Shiyou Li Beijing Institute of Genomics Chinese Academy of Sciences School of Chinese MateriaMedica Beijing University of Chinese Medicine Department of Immunology Duke University Medical Center

Purpose: The survival and prognosis of glioblastoma(GBM) patients withsame tumor histology and classification oftenhave significant differences. There is a need of biomarkers to better classify patients by their survival, prognosis and/or disease risk to provide ***-40, a secreted protein overexpressed in glioblastoma, whichplays a critical role in the pathogenesis anddevelopment of glioblastoma. Wehypothesize YKL-40 could be used as a biomarker of glioblastoma, that may aid in the classification of GBM patients and provide reasonable treatment decisions. Experimental Design:We analyzed YKL-40 transcript expression level of 45 Chinese high-grade glioblastoma(WHO grade Ⅳ), and used mRNA-seq datafrom The Cancer Genome Atlas(TCGA) database to investigate the correlation of YKL-40 expression level with the prognosis and survival of GBM *** obtained and analyzed GBM patients mRNA-seq data fromTCGA database, and used qPCR and ELISA analysis to further study the correlation between YKL-40 and adenosine receptor A2 A. Results:We founda negative correlation between the expression level of YKL-40 in glioblastoma patients and their survival time(r=0.33,Pher expression level of YKL-40 havepoor prognosis andsurvival. On the contrary, thepatientswith lower YKL-40 expression have more favorable prognosis *** activation of adenosine receptor A2 A significantly promoted the expression of YKL-40 and MMP-9,YKL-40 and MMP-9 potentially promoted the invasion of U87-MG *** blockade of adenosine receptor A2 Asignificantly inhibited the expression of YKL-40 and MMP-9, thereby significantly inhibited the invasion of U87-MG cells. Conclusions:Our work analyzed and verified that YKL-40 could be used as a potential clinical biomarker of glioblastoma, with which toclassify GBM patients by theirdisease risk, prognosis andresponse to *** results suggested that adenosine receptor inhibitors may be useddepend on

关键词： Glioblastoma YKL-40 Biomarker A2A MMP-9 Istradefylline

来源： cnki会议评论

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化学学报 2008年第1期66卷 56-62页

作者：刘秋叶李文友何锡文陈朗星张玉奎南开大学化学学院天津300071

选用马来酸酐修饰的硅胶作为载体,丙烯酰胺为功能单体,N,N'-亚甲基双丙烯酰胺为交联剂,牛血红蛋白为模板分子,采用氧化还原悬浮聚合法,合成了具有选择性识别的牛血红蛋白分子印迹聚合物.并用红外光谱(IR)、扫描电子显微镜(SEM)和元素分... 详细信息

选用马来酸酐修饰的硅胶作为载体,丙烯酰胺为功能单体,N,N'-亚甲基双丙烯酰胺为交联剂,牛血红蛋白为模板分子,采用氧化还原悬浮聚合法,合成了具有选择性识别的牛血红蛋白分子印迹聚合物.并用红外光谱(IR)、扫描电子显微镜(SEM)和元素分析对聚合物进行了表征,结果表明载体表面成功地接枝了分子印迹聚合物薄层.同时选择性吸附实验表明分子印迹聚合物具有良好的识别性能,能实现水溶液中牛血红蛋白的富集.

关键词：表面修饰分子印迹聚合物牛血红蛋白硅胶接枝氧化还原聚合