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TAR DNA-Binding Protein 43 is Cleaved by the Protease 3C of Enterovirus A71

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Virologica Sinica 2021年第1期36卷 95-103页

作者： Xiaoman Wo Yuan Yuan Yong Xu Yang Chen Yao Wang Shuoxuan Zhao lexun lin Xiaoyan Zhong Yan Wang Zhaohua Zhong Wenran Zhao Department of Cell Biology Harbin Medical UniversityHarbin 150081China Department of Microbiology Harbin Medical UniversityHarbin 150081China

Enterovirus A71(EV-A71)is one of the etiological pathogens leading to hand,foot,and mouth disease(HFMD),which can cause severe neurological *** neuropathogenesis of EV-A71 infection is not well *** mislocalization and aggregation of TAR DNA-binding protein 43(TDP-43)is the pathological hallmark of amyotrophic lateral sclerosis(ALS).However,whether TDP-43 was impacted by EV-A71 infection is *** study demonstrated that TDP-43 was cleaved during EV-A71 *** cleavage of TDP-43 requires EV-A71 replication rather than the activated caspases due to viral ***-43 is cleaved by viral protease 3 C between the residues 331 Q and332 S,while mutated TDP-43(Q331 A)was not *** addition,mutated 3 C which lacks the protease activity failed to induce TDP-43 *** also found that TDP-43 was translocated from the nucleus to the cytoplasm,and the mislocalization of TDP-43 was induced by viral protease 2 A rather than 3 *** together,we demonstrated that TDP-43 was cleaved by viral protease and translocated to the cytoplasm during EV-A71 infection,implicating the possible involvement of TDP-43 in the pathogenesis of EV-A71 infection.

关键词： Enterovirus A71(EV-A71) TAR DNA-binding protein 43(TDP-43) 3C protease 2A protease

Stress Granule Formation is One of the Early Antiviral Mechanisms for Host Cells Against Coxsackievirus B Infection

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Virologica Sinica 2018年第4期33卷 314-322页

作者： Xia Zhai Shuo Wu lexun lin Tianying Wang Xiaoyan Zhong Yang Chen Weizhen Xu Lei Tong Yan Wang Wenran Zhao Zhaohua Zhong Department of Microbiology Harbin Medical University Harbin 150081 China Department of Cell Biology Harbin Medical University Harbin 150081 China

Stress granules(SGs) are intracellular granules formed when cellular translation is blocked and have been reported to be involved in a variety of viral infections. Our previous studies revealed that SGs are involved in the coxsackievirus B(CVB)infection process, but the role of SGs in CVB infection has not been fully explored. In this study, we found that CVB type 3(CVB3) could induce SG formation in the early phase of infection. Results showed that levels of CVB3 RNA and protein were significantly inhibited during the early stage of CVB3 infection by the elevated formation of SGs, while viral RNA and protein synthesis were significantly promoted when SG formation was blocked. Our findings suggest that SG formation is one of the early antiviral mechanisms for host cells against CVB infection.

关键词： Coxsackievirus B (CVB) Stress granule (SG) Viral replication

Expression Profile and Function Analysis of Long Non-coding RNAs in the Infection of Coxsackievirus B3

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Virologica Sinica 2019年第6期34卷 618-630页

作者： Lei Tong Ye Qiu Hui Wang Yunyue Qu Yuanbo Zhao lexun lin Yan Wang Weizhen Xu Wenran Zhao Hongyan He Guangze Zhao Mary HZhang Decheng Yang Xingyi Ge Zhaohua Zhong Department of Microbiology Harbin Medical UniversityHarbin 150081China College of Biology Hunan UniversityChangsha 410012China Department of Cell Biology Harbin Medical UniversityHarbin 150081China Department of Pathology and Laboratory Medicine University of British ColumbiaVancouverBC V6Z 1Y6Canada

The roles of lnc RNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3(CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lnc RNAs in enterovirus infection. We profiled lnc RNAs and m RNA expression in CVB3-infected He La cells by lnc RNA-m RNA integrated microarrays. As a result, 700 differentially expressed lnc RNAs(431 up-regulated and 269 down-regulated) and665 differentially expressed m RNAs(299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lnc RNA-m RNA integrated pathway analysis to identify potential functional impacts of the differentially expressed m RNAs, in which lnc RNA-m RNA correlation network was built. According to lnc RNA-m RNA correlation, we found that XLOC-001188, an lnc RNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 m RNA,an anti-CVB3 gene reported previously. This interaction was supported by q PCR detection following si RNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 m RNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lnc RNAs, SNHG11, RP11-145 F16.2, RP11-1023 L17.1 and RP11-1021 N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2 BP1. In all, our studies reveal the alteration of lnc RNA expression in CVB3 infection and its potential influence on CVB3 replication,providing useful information for future studies of enterovirus infection.

关键词： Coxsackievirus B3(CVB3) lncRNA-mRNA correlation network Long non-coding RNA(lncRNA) XLOC-001188 NFAT5

Curcumin inhibits the replication of enterovirus 71 in vitro

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Acta Pharmaceutica Sinica B 2014年第4期4卷 284-294页

作者： Ying Qin lexun lin Yang Chen Shuo Wu Xiaoning Si Heng Wu Xia Zhai Yan Wang Lei Tong Bo Pan Xiaoyan Zhong Tianying Wang Wenran Zhao Zhaohua Zhong Department of Microbiology Harbin Medical UniversityHarbin 150086China Department of Cell Biology Harbin Medical UniversityHarbin 150086China

Human enterovirus 71(EV71)is the main causative pathogen of hand,foot,and mouth disease(HFMD)in *** epidemic of HFMD has been a public health problem in Asia-Pacific region for decades,and no vaccine and effective antiviral medicine are *** has been used as a traditional medicine for centuries to treat a diversity of disorders including viral *** this study,we demonstrated that curcumin showed potent antiviral effect again *** Vero cells infected with EV71,the addition of curcumin significantly suppressed the synthesis of viral RNA,the expression of viral protein,and the overall production of viral *** with the previous reports,curcumin reduced the production of ROS induced by viral ***,the antioxidant property of curcumin did not contribute to its antiviral activity,since N-acetyl-L-cysteine,the potent antioxidant failed to suppress viral *** study also showed that extracellular signal-regulated kinase(ERK)was activated by either viral infection or curcumin treatment,but the activated ERK did not interfere with the antiviral effect of curcumin,indicating ERK is not involved in the antiviral mechanism of *** the previous reports that curcumin inhibited protein degradation through ubiquitin–proteasome system(UPS),we found that curcumin had no impact on UPS in control ***,curcumin did reduce the activity of proteasomes which was increased by viral *** addition,the accumulation of the short-lived proteins,p53 and p21,was increased by the treatment of curcumin in EV71-infected *** further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB,both of which are required for the formation of viral replication *** found that curcumin significantly reduced the level of both ***,the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral *** also de

关键词： Curcumin Enterovirus 71 Viral replication GBF1 PI4KB Ubiquitin–proteasome system Apoptosis

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细胞焦亡在肠道病毒A71型感染中的作用

病毒学报 2020年第6期36卷 1043-1049页

作者：林乐勋陈阳郎秀娟哈尔滨医科大学基础医学院哈尔滨150086

肠道病毒A组71型(Enterovirus A71,EV-A71)是引起手足口病(Hand,foot,and mouth disease,HFMD)最常见的病原体之一,而细胞焦亡是一种以细胞溶解及炎症反应为主要特征的细胞程序性死亡。目前细胞焦亡参与EV-A71致病的分子机制尚不清楚。... 详细信息

肠道病毒A组71型(Enterovirus A71,EV-A71)是引起手足口病(Hand,foot,and mouth disease,HFMD)最常见的病原体之一,而细胞焦亡是一种以细胞溶解及炎症反应为主要特征的细胞程序性死亡。目前细胞焦亡参与EV-A71致病的分子机制尚不清楚。本研究旨在探索EV-A71感染引起的焦亡与病毒感染之间的关系。EV-A71感染Vero细胞,6 h后检测caspase-1 mRNA和蛋白的表达水平,结果显示EV-A71感染促使caspase-1表达升高,表明EV-A71感染引起细胞焦亡;检测IL-1β和IL-18 mRNA和蛋白的表达水平,结果显示EV-A71感染促进IL-1β和IL-18的表达升高,表明EV-A71诱导的焦亡与炎症的产生有关。EV-A71感染后加入caspase-1抑制剂Ac-YVADCMK,在感染后6 h检测caspase-1和EV-A71的mRNA和蛋白的表达水平,结果显示加入Ac-YVAD-CMK可降低caspase-1和EV-A71的mRNA及蛋白水平,表明Ac-YVAD-CMK可抑制细胞焦亡和病毒的感染;检测IL-1β和IL-18 mRNA和蛋白的表达水平,结果显示加入Ac-YVAD-CMK可降低IL-1β和IL-18的表达,表明抑制焦亡可抑制炎症反应。本研究得出结论是EV-A71感染可诱导caspase-1介导的细胞焦亡,抑制caspase-1可有效抑制病毒感染。

关键词：肠道病毒A71型(EV-A71) 细胞焦亡病毒感染

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医学微生物学自主设计性实验教学探索

南方医学教育 2019年第3期 34-35,45页

作者：林乐勋王慧佟雷钟照华哈尔滨医科大学基础医学院病原实验教学中心黑龙江哈尔滨150086 哈尔滨医科大学基础医学院微生物教研室黑龙江哈尔滨150086

在培养高素质创新人才的教育目标下,传统的讲授性医学微生物学实验教学的弊端日益凸显,需要在实验教学中引入新的教学模式。自主设计性实验能够让学生全程参与实验设计、实施、结果分析与总结,充分激发学生的积极性与主动性,培养学生理... 详细信息

在培养高素质创新人才的教育目标下,传统的讲授性医学微生物学实验教学的弊端日益凸显,需要在实验教学中引入新的教学模式。自主设计性实验能够让学生全程参与实验设计、实施、结果分析与总结,充分激发学生的积极性与主动性,培养学生理论联系实际的能力,为创新能力和科研素质的培养奠定基础。

关键词：医学微生物学实验自主设计性实验创新能力

探索口腔医学博士教育与专科医师规培并轨的模式

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中国继续医学教育 2020年第1期12卷 53-55页

作者：宋蓉任丽萍林乐勋哈尔滨医科大学附属第一医院口腔修复科黑龙江哈尔滨150001 哈尔滨医科大学基础医学院黑龙江哈尔滨150081

国家口腔医学博士教育与专科医师规培并轨的模式现已全面实施且成效显著。而口腔博士专业学位教育方面,仍然是沿袭传统方式。本文旨通过文献查阅、医院调查、专家访谈等研究方法,在我国“5+3”培养模式的基础上,探讨口腔医学博士教育与... 详细信息

国家口腔医学博士教育与专科医师规培并轨的模式现已全面实施且成效显著。而口腔博士专业学位教育方面,仍然是沿袭传统方式。本文旨通过文献查阅、医院调查、专家访谈等研究方法,在我国“5+3”培养模式的基础上,探讨口腔医学博士教育与专科医师规培并轨的模式的可行培养方式,提出当前情况下两种培养体系结合所面临的困难,准确了解二者的共性的问题,缩小二者之间的差异,通过多举措并行构建合理的并轨培养方式,解决口腔博士专业学位与专科医师规范培训存在的问题和关键,为改革试点提供参考依据,助力并轨培养取得成功。

关键词：口腔医学博士专业学位教育住院医师规范化培训并轨

口腔医学生早期接触临床教育模式的应用与体会

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继续医学教育 2021年第10期35卷 51-53页

作者：宋蓉林乐勋张衡芳任丽萍哈尔滨医科大学附属第一医院口腔修复科黑龙江哈尔滨150001 哈尔滨医科大学基础医学院黑龙江哈尔滨150081

口腔医学生早期接触临床教育模式的构建和实施是当今口腔医学教育教改的核心内容之一。学校、医院密切配合,做好课程内容的设计和教学过程的组织协调工作。将“早临床、多临床、反复临床”的教育理念贯穿于口腔医学人才培养的全过程。... 详细信息

口腔医学生早期接触临床教育模式的构建和实施是当今口腔医学教育教改的核心内容之一。学校、医院密切配合,做好课程内容的设计和教学过程的组织协调工作。将“早临床、多临床、反复临床”的教育理念贯穿于口腔医学人才培养的全过程。实施口腔医学生早期接触临床教育模式,极大地促进了口腔医学生学习专业知识的热情和决心,提高了学习的兴趣;同时带教教师更加注重言传身教,努力提升自身业务水平。早期接触临床教育模式体现了基础课程和临床课程之间的双向渗透和重组,做到基础教学中有临床,临床阶段有基础,学生早期接触口腔临床。

关键词：早接触临床教育模式医学教育口腔医学基础教学医学生培养

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数字化微笑设计技术在口腔美学教学中的实施

中国继续医学教育 2020年第4期12卷 54-56页

作者：宋蓉林乐勋谢伟丽任丽萍哈尔滨医科大学附属第一医院口腔修复科黑龙江哈尔滨150001 哈尔滨医科大学基础医学院黑龙江哈尔滨150081

口腔美学是临床修复的重要内容,数字化微笑设计技术以口腔美学标准为基本准则,使临床医生通过计算机软件将按特殊要求精确拍摄的照片进行美学分析和设计,操作前就实现精确的美学评估,预测评估修复后美学与功能的效果,并展示给患者,帮助... 详细信息

口腔美学是临床修复的重要内容,数字化微笑设计技术以口腔美学标准为基本准则,使临床医生通过计算机软件将按特殊要求精确拍摄的照片进行美学分析和设计,操作前就实现精确的美学评估,预测评估修复后美学与功能的效果,并展示给患者,帮助临床医生做出合适的临床决策。将数字微笑设计技术引进口腔美学教学,通过理论学习和实际操作,使学生初步掌握数字化微笑技术的基本原理和流程,并在临床操作中逐步实施,逐步缩短临床和实习间差距,为将来临床工作顺利过渡奠定坚实的基础。在教学实施中总结积累经验,使口腔美学这门课程的不断丰富和完善。

关键词：数字化微笑设计口腔美学教学标准临床实习精准拍摄