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TP53BP2:Roles in suppressing tumorigenesis and therapeutic opportunities

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Genes & Diseases 2023年第5期10卷 1982-1993页

作者： Yunfei Huo Ke Cao Buxin Kou Mengyin Chai Shuangshuang Dou dexi chen Ying Shi Xiaoni Liu Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Malignant tumor is still a major problem *** tumorigenesis or tumor development,tumor suppressor p53-binding protein 2(TP53BP2),also known as apoptosis stimulating protein 2 of p53(ASPP2),plays a critical role in p53 dependent and independent *** of TP53BP2 is highly correlated with the prognosis and survival rate of malignant tumor ***53BP2 can interact with p53,NF-κB p65,Bcl-2,HCV core protein,PP1,YAP,CagA,RAS,PAR3,and other proteins to regulate cell ***,TP53BP2 can also regulate the proliferation,apoptosis,autophagy,migration,EMT and drug resistance of tumor cells through downstream signaling pathways,such as NF-κB,RAS/MAPK,mevalonate,TGF-β1,PI3K/AKT,aPKC-ι/GLI1 and autophagy *** a potential therapeutic target,TP53BP2 has been attracted more *** review the role of TP53BP2 in tumorigenesis or tumor development and the signal pathway involved in TP53BP2,which may provide more deep insight and strategies for tumor treatment.

关键词： Binding proteins Signaling pathways TP53 TP53BP2 Tumorigenesis Tumor development

Hepatitis B Virus Induces Microtubule Stabilization to Promote Productive Infection through Upregulating Microtubule-associated Protein 1S

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 467-473页

作者： Yuanyue Guan Bin Sun Shijie Zhang Yuan Zhuang Yanxiang Huang Minghua Lin Rongling Zheng dexi chen Ying Shi Yanjun Wang Department of Beijing Institute of Hepatology Beijing You An HospitalCapital Medical UniversityBeijingChina Department of Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Beijing You An HospitalCapital Medical UniversityBeijingChina Department of Intervention Therapy Center of Tumor and Liver Diseases Beijing You An HospitalCapital Medical UniversityBeijingChina Department of Pathology Beijing You An HospitalCapital Medical UniversityBeijingChina Clinical Laboratory Center Beijing You An HospitalCapital Medical UniversityBeijingChina

Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)***,the mechanism of HBV-host interaction for optimal viral transport is ***,we aimed to explore how HBV manipulates microtubule-associated protein 1S(MAP1S)and microtubule(MT)to facilitate its transport and ***:The expression of MAP1S or acetylated MT was investigated by immunofluorescence,RT-PCR,immunoblotting,and plasmid ***1S overexpression or knockdown was performed by lentiviral infection or shRNA transfection,*** DNA was quantified using ***:Significantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR(p<0.01)and immunoblotting(p<0.001).Notably,stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy ***1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside ***,transfection with the hepatitis B virus X protein(HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls(p<0.0001),whereas HBVX−mutant-encoding HBV proteins(surface antigen,core protein,and viral DNA polymerase)hardly affected its ***:These results demonstrate that HBx induces the forma tion of stable MTs to promote the release of HBV particles through upregulating ***,our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation,and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.

关键词： Hepatitis B virus Hepatitis B virus X protein Microtubule Microtubule-associated protein 1S

Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

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Cellular & Molecular Immunology 2015年第5期12卷 604-614页

作者： Zhen Li Yanmei Jiao Yu Hu Lianxian Cui dexi chen Hao Wu Jianmin Zhang Wei He Department of Immunology School of Basic Medicine Peking Union Medical College & Institute of Basic Medical Sciences Chinese Academy of Medical Sciences State Key Laboratory of Medical Molecular Biology Beijing China Beijing Key Laboratory of AIDS Center for Infectious Diseases Beijing You'An Hospital Capital Medical University Beijing China Beijing Institute of Liver Disease Beijing You'An Hospital Capital Medical University Beijing China

γδT cells play important roles in innate immunity as the first-line of defense against infectious diseases. Human immunodeficiency virus （HIV） infection disrupts the balance between Vδ1 T cells and Vδ2 T cells and causes dysfunction among γδ T cells. However, the biological mechanisms and clinical consequences of this disruption require further investigation. In this study, we performed a comprehensive analysis of phenotype and function of memory γδ T cells in cohorts of Chinese individuals with HIV infection. We found a dynamic change in memory Vδ2 γδ T cells, skewed toward an activated and terminally differentiated effector memory phenotype TEMRA Vδ2 γδT cell, which may account for the dysfunction of Vδ2 γδT cells in HIV disease. In addition, we found that IL-17-producing γδ T cells were significantly increased in HIV-infected patients with fast disease progression and positively correlated with HLA-DR＋ γδ T cells and CD38＋HLA-DR＋ γδ T cells. This suggests the IL-17 signaling pathway is involved in γδ T-cell activation and HIV pathogenesis. Our findings provide novel insights into the role of Vδ2 T cells during HIV pathogenesis and represent a sound basis on which to consider immune therapies with these cells.

关键词： γδT cell HIV IL-17 immune activation memory Vδ2 γδ T cells

Curcumin ameliorates hippocampal neuron damage induced by human immunodeficiency virus-1

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Neural Regeneration Research 2013年第15期8卷 1368-1375页

作者： Hongmei Tang Rui Pan Wenli Fang Yanyan Xing dexi chen Xiaobao chen Yuanyuan Yu Junbing Wang Zheng Gong Guoyin Xiong Jun Dong Department of Pathophysiology Key Laboratory of State Administration of Traditional Chinese Medicine Medical College of Jinan University Institute of Brain Research Medical College of Jinan University Joint Laboratory for Brain Function and Health of Jinan University and the University of Hong Kong Department of Orthopedics First Affiliated Hospital Medical College of Jinan University STD/AIDS Research Lab Beijing Youan Hospital Capital Medical University

Our previous studies have shown that infection with the gp120 V3 loop can cause human immunodeficiency virus-1 associated neurocognitive disorders. Curcumin has been shown to improve these effects to some degree, but the precise mechanisms remain unknown. The present study analyzed the neuroprotective effect and mechanism of curcumin in relation to hippocampal neurons. Results showed that 1 nmol/L gp120 V3 loop suppressed the growth of synapses. After administration of 1 !umol/L curcumin, synaptic growth improved. Curcumin is neuroprotective against gp120 V3 loop-induced neuronal damage by inhibiting the activation of L-type calcium currents, relieving intracellular Ca^2＋ overload, promoting Bcl-2 expression, and inhibiting Bax activation. The effect of curcumin was identical to nimodipine, suggesting that curcumin has the same neuroprotective effects against gp120 V3 loop-induced neuronal damage.

关键词： neural regeneration traditional Chinese medicine curcumin gp120 V3 loop humanimmunodeficiency virus-1 associated neurocognitive disorders Ca^2+ synapse apoptosis grants-supported paper neuroregeneration

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论新媒体时代高校的马克思主义传播

扬州大学学报（高教研究版） 2023年第3期27卷 97-103页

作者：陈德玺惠州学院广东惠州516007

新媒体时代马克思主义在高校传播的主要特征是主体与客体扁平化、内容与方式多样化、成效与时效可视化;基本规律是从经典向大众转换、回归理论初心,从理论向生活转换、回答现实问题,从单向向多维转换、多主体共建共享;主要挑战是多元话... 详细信息

新媒体时代马克思主义在高校传播的主要特征是主体与客体扁平化、内容与方式多样化、成效与时效可视化;基本规律是从经典向大众转换、回归理论初心,从理论向生活转换、回答现实问题,从单向向多维转换、多主体共建共享;主要挑战是多元话语弱化主流话语风险长期存在、专业话语弱化政治话语风险转变困难、虚拟话语弱化实体话语风险持续走高。未来,马克思主义在高校传播的力度将前所未有、方式将更加便捷、信心将更加充足。

关键词：新媒体时代高校思政教育马克思主义中国化

High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients

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Cellular & Molecular Immunology 2020年第6期17卷 650-652页

作者： Wenjing Wang Bin Su Lijun Pang Luxin Qiao Yingmei Feng Yabo Ouyang Xianghua Guo Hongbo Shi Feili Wei Xiaogang Su Jiming Yin Ronghua Jin dexi chen Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University100069 BeijingChina Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer 100069 BeijingChina Center for Infectious Diseases Beijing Youan HospitalCapital Medical University100069 BeijingChina

The outbreak of coronavirus disease 2019(COVID-19)caused by the new virus SARS-CoV-2 has been announced as a public health emergency of international concern.1–3 The clinical features of patients with COVID-19 range from common fever and cough to other rare symptoms,such as diarrhea and *** disease can progress quickly,and 2–3%of patients die within a short time,which is generally due to multiple organ failure.4–7 Clinically,COVID-19 patients are classified into mild,moderate,severe,and critical cases.5–7 The immune response against SARS-CoV-2 is probably linked to the severity of ***,Zheng et al.8 showed that elevated levels of T-cell exhaustion and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients;however,a more comprehensive understanding of the pathology of SARS-CoV-2 infection remains to be ***,we profiled immune cellular components using mass cytometry(CyTOF)to analyze the peripheral blood mononuclear cells(PBMCs)from patients with differences in disease progression by comparing with the PBMCs from healthy donors(HDs).

关键词： patients immunity elevated

Endoplasmic Reticulum Stress Activated-Glycogen Synthase Kinase 3β Aggravates Liver Inflammation and Hepatotoxicity in Mice with Acute Liver Failure

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Endoplasmic Reticulum Stress Activated-Glycogen Synthase Kin...

外周血T淋巴细胞CD4表达水平在肝移植肝癌复发诊断及预后评估中的价值

中华医学会第十三次全国感染病学术会议

作者： Feng Ren Xiangying Zhang Yu chen dexi chen Zhongping Duan Beijing YouAn Hospital Capital Medical University

Background&Aims Endoplasmic reticulum stress(ER stress)has been increasingly recognized as an important mechanism in various liver ***,its intrinsic physiological role in acute liver failure(ALF)remains largely *** study aimed to examine how ER stress orchestrates glycogen synthase kinase 315(GSK313)and inflammation to affect *** In a murine ALF model induced by D-gaiactosamine(D-GaIN)and lipopolysaccharide(LPS),4-Phenylbutyric aeid(4-PBA)is to be administered to re-

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中华检验医学杂志 2023年第1期46卷 68-73页

作者：刘宁张权于艳华陈德喜娄金丽首都医科大学附属北京佑安医院检验科北京100069 首都医科大学附属北京佑安医院科研处北京100069 北京市肝病研究所北京100069

目的探讨外周血T淋巴细胞CD4表达水平在肝移植肝癌复发患者诊断与预后评估中的价值。方法回顾性分析2014年1月至2016年12月在北京佑安医院肝移植中心进行肝移植治疗和5年随访的50例肝癌患者的临床资料与实验室资料,比较肝移植肝癌复发组... 详细信息

目的探讨外周血T淋巴细胞CD4表达水平在肝移植肝癌复发患者诊断与预后评估中的价值。方法回顾性分析2014年1月至2016年12月在北京佑安医院肝移植中心进行肝移植治疗和5年随访的50例肝癌患者的临床资料与实验室资料,比较肝移植肝癌复发组(29例)和未复发组(21例)患者肝功能、血常规、肿瘤标志物、外周血T淋巴细胞分类等实验室指标及5年生存情况,用Spearman相关性分析各临床指标与肝移植肝癌复发的相关性,采用受试者工作特征(ROC)曲线分析T淋巴细胞CD4表达水平对肝移植肝癌复发的诊断效能,采用Kaplan-Meier生存曲线比较不同CD4表达水平患者的生存差异。结果与肝移植肝癌未复发组比较,复发组丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、白蛋白、淋巴细胞、甲胎蛋白、维生素K缺乏或拮抗剂诱导的蛋白质Ⅱ、CD3+、CD4+、CD8+T表达水平差异有统计学意义(P均265.50个/μl组[15.0(10.0,36.8)个月比53.0(19.5,60.0)个月,P<0.05]。结论外周血T淋巴细胞CD4表达水平与肝移植肝癌复发呈负相关,CD4+T淋巴细胞取265.50个/μl时对肝移植肝癌复发的临床诊断与预后评估具有较高的价值。

关键词：肝移植肿瘤CD4阳性T淋巴细胞诊断预后

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长期使用核苷类似物中枢神经线粒体毒性研究

长期使用核苷类似物中枢神经线粒体毒性研究