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Serum levels of mi RNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

Hepatobiliary & Pancreatic diseases International 2018年第2期17卷 126-132页

作者： Ya Wen Shi-Fang Peng Lei Fu Xiao-Yu Fu Da-Xian Wu Bing-Jie Liu De-Ming Tan Yi Ouyang Key laboratory of Hunan viral Hepatitis Department of Infectious Disease Xiangya Hospital Central South University

Background: Hepatitis B virus(HBV)-associated acute-on-chronic liver failure(HBV-ACLF) is a lifethreatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum mi RNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ***: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to30 chronic asymptomatic HBV carriers as controls. The mi RNAs expressions were measured by real-time quantitative PCR(q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed mi RNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive ***: Real-time q-PCR indicated that serum miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and mi R-122-3 p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+-1.72 × INR-4.963 × gastrointestinal bleeding(Yes = 0; No = 1)-0.278 ×(mi R-122-3 p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve(AUROC) was ***: Expression levels of these mi RNAs(miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

关键词： MicroRNA Hepatitis B virus Acute-on-chronic liver failure Prognosis

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TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu Linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng Yu Li Shen Xiaochun Zhang Aijun Sun Junbo Ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key laboratory of viral Heart diseases National Health CommissionShanghaiChina Key laboratory of viral Heart diseases Chinese Academy of Medical SciencesShanghaiChina National Clinical Research Center for Interventional Medicine ShanghaiChina Department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina Institutes of Biomedical Sciences Fudan UniversityShanghaiChina Shanghai Institute of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4

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SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening

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Virologica Sinica 2019年第5期34卷 508-520页

作者： Tiezhu Liu Jiajia Li Yang Liu Yuanyuan Qu Aqian Li Chuan Li Quanfu Zhang Wei Wu Jiandong Li Yan Liu Dexin Li Shiwen Wang Mifang Liang Key laboratory of Medical Virology and viral diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China CDC-WIV Joint Research Center for Emerging diseases and Biosafety Wuhan 430071China Department of Microbiology Anhui Medical UniversityHefei 230032China The First Affiliated Hospital of Anhui Medical University Hefei 230022China

Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in *** molecular mechanisms and host cellular factors required for SFTSV infection remain *** a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV *** SNX11-KO HeLa cell line was established,and SFTSV replication was significantly *** glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi *** values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO ***,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking *** study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.

关键词： CRISPR screen Severe fever with thrombocytopenia syndrome virus(SFTSV) Host factor Sorting nexin 11(SNX11)

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Is liver biopsy still needed in children with chronic viral hepatitis?

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World Journal of Gastroenterology 2015年第42期21卷 12141-12149页

作者： Maria Pokorska-?piewak Barbara Kowalik-Miko?ajewska Ma?gorzata Aniszewska Magdalena Pluta Magdalena Marczyńska Department of Children’s Infectious diseases Medical University of Warsaw Warsaw Hospital for Infectious diseases

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression(grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies(elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

关键词： Liver biopsy Hepatitis B Hepatitis C Pathology Ela

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Antibody Response to COVID-19 Virus--Heilongjiang Province and Gansu Province,China,2020

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China CDC weekly 2020年第34期2卷 645-650页

作者： Naiying Mao Zhen Zhu Shuangli Zhu Deshan Yu Jun Xu Aili Cui Lei Cao Jinyuan Guo Huiling Wang Dongyan Wang Dongmei Yan Yang Song Qian Yang Zhongyi Jiang Hui Zhang Chang Shu Ming Yang Yanhai Wang Jinbo Xiao Zhenzhi Han Yong Zhang Yan Zhang Wenbo Xu NHC Key laboratory of Medical Virology and viral diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Gansu Provincial Center for Disease Control and Prevention LanzhouGansuChina Heilongjiang Provincial Center for Disease Control and Prevention HaerbinHeilongjiangChina

What is already known about this topic?Coronavirus disease 2019(COVID-19)has become a global pandemic,while the profile of antibody response against the COVID-19 virus has not been well *** is added by this report?In this study,210 serum samples from 160 confirmed COVID-19 cases with different disease severities were *** IgM,IgA,IgG,and neutralizing antibodies(NAb)against COVID-19 virus were *** findings indicated that four antibodies could be detectable at low levels within 2 weeks of disease onset,then rapidly increasing and peaking from the 3^(rd) to 5^(th) *** decreased between 5^(th) and 9^(th) Weeks,and a higher IgM/IgA level was observed in the groups with mild/moderate severity within 2 weeks(p<0.05),while all 4 types of antibodies were higher in the group with severe/critical severity after 4 weeks(p<0.05).What are the implications for public health practice?Our study on the dynamics of serological antibody responses against COVID-19 virus among COVID-19 patients complements the recognition regarding the humoral immune response to COVID-19 virus *** findings will help in the interpretation of antibody detection results for COVID-19 patients and be beneficial for the evaluation of vaccination effects.

关键词： COV finding fir

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Role of the blood-brain barrier in rabies virus infection and protection

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Protein & Cell 2013年第12期4卷 901-903页

作者： Lihua Wang Yuxi Cao Qing Tang Guodong Liang State Key laboratory for Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Rabies is an acute,progressive encephalitis caused by infection with rabies virus(RABV).It is one of the most important zoonotic infections and causes more than 70,000 human deaths annually(http://***).It has long been held that a rabies infection is lethal in humans once the causative RABV reaches the central nervous system(CNS);however,this concept was challenged by the recent recovery of a small number of rabies *** analysis of these patients revealed that the blood-brain barrier(BBB)played a major role in protection against the *** main reason for the survival of these patients was enhanced BBB permeability after infection with the causative agent(usually bat-originated RABV showing reduced pathogenicity),which allowed immune cells to enter the tissues of the CNS and clear the infection(Willoughby et al.,2005).These fi ndings have been confi rmed in animal infection experiments(Wang et al.,2005;Roy and Hooper,2007,2008;Faber et al.,2009).Thus,the BBB has attracted the attention of scientists interested in the pathogenesis of,and therapeutic approaches,for *** paper introduces the role of the BBB in rabies infections and protection of the CNS and provides insight into future treatments for patients with clinical rabies.

关键词： rabies infection barrier

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How does Cellular Heparan Sulfate Function in viral Pathogenicity?

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Biomedical and Environmental Sciences 2011年第1期24卷 81-87页

作者： ZHU WuYang LI JiangJiao LIANG GuoDong Department of viral Encephalitis Institute for Viral Disease Control and Prevention Chinese Center forDisease Control and Prevention and State Key Laboratory for Infectious Disease Prevention and Control(SKLID) Beijing 100052 China

Heparan sulfate （HS） is ubiquitously expressed on the surfaces and in the extracellular matrix of virtually all cell types, making it an ideal receptor for viral infection. Compared with wild‐type viruses, cell culture‐adapted laboratory strains exhibit more efficient binding to cellular HS receptors. HS‐binding viruses are typically cleared faster from the circulation and cause lower viremia than their non‐HS‐binding counterparts, suggesting that the HS‐binding phenotype is a tissue culture adaptation that lowers virus fitness in vivo. However, when inoculated intracranially, efficient cell attachment through HS binding can contribute to viral neurovirulence. The primary aim of this review is to discuss the roles of HS binding in viral pathogenicity, including peripheral virulence and neurovirulence. Understanding how heparan sulfate functions during virus infection in vivo may prove critical for elucidating the molecular mechanism of viral pathogenesis, and may contribute to the development of therapeutics targeting HS.

关键词： Heparan sulfate viral pathogenicity Receptor

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The Susceptibility of Primary Dermis Fibroblasts from the Chinese Tree Shrew to Human Cytomegalovirus Infection

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Virologica Sinica 2019年第3期34卷 270-277页

作者： Shu-Wei Dong Ling-Shuai Jiao Ming Yang Ying-Liang Duan Yi-Bo Chen Fei Zhao A-Mei Zhang Li Liu Min-Hua Luo Xue-Shan Xia Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China The Key laboratory of Tropical and Subtropical Animal viral diseases in Yunnan Province Kunming 650224China State Key laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China

As a universal pathogen leading to neonatal defects and transplant failure,human cytomegalovirus(HCMV)has strict species specificity and this has prevented the development of a suitable animal model for the pathogenesis *** mechanism of cross-species barrier remains elusive and there are so far no non-human cell culture models that support HCMV *** Chinese tree shrew(Tupaia belangeri chinensis)is a small laboratory animal and evolutionary closely related with *** investigated the susceptibility of primary tree shrew dermis fibroblasts(TSDF)to HCMV *** with a GFP-expressing HCMV virus resulted in green fluorescence in infected cells with the expression of IE1,UL44 and *** titers of cell-free viruses reached 10^3 PFU/mL at 96 hpi,compared to titers of 10^4 PFU/mL observed in primary human foreskin *** results suggested that TSDF was semi-permissive for HCMV *** TSDF model could be further used to investigate key factors influencing cross-species multiplication of HCMV.

关键词： Human cytomegalovirus(HCMV) Primary tree shrew dermis fibroblasts(TSDF) Cross-species infection Semi-permissiveness

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Interactions Between TLR7 and TLR9 Agonists and Receptors Regulate Innate Immune Responses by Astrocytes and Microglia

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神经损伤与功能重建 2010年第2期5卷 122-134页

作者： NIRANJAN B. BUTCHI MIN DU KARIN E. PETERSON laboratory of Persistent viral diseases Rocky Mountain LaboratoriesNational Institute of Allergy and Infectious Diseases

Toll样受体7(TLR7)和Toll样受体9(TLR9)是固有免疫反应中的重要介质。它们均定位于内涵体间隔,识别核酸和经过髓样分化因子88(MyD88)传导来的信号。本文分析TLR7和TLR9导致的在中枢神经系统固有免疫反应中起作用的星形胶质细胞和小胶质... 详细信息

Toll样受体7(TLR7)和Toll样受体9(TLR9)是固有免疫反应中的重要介质。它们均定位于内涵体间隔,识别核酸和经过髓样分化因子88(MyD88)传导来的信号。本文分析TLR7和TLR9导致的在中枢神经系统固有免疫反应中起作用的星形胶质细胞和小胶质细胞的活化。TLR7和TLR9激动剂引起星形胶质细胞和小胶质细胞相似的细胞因子反应,但二者仍有区别,小胶质细胞产生抗炎因子IL-10、抗凋亡因子G-CSF及IL-9,但星形胶质细胞不产生。对2种细胞的共刺激研究均显示,TLR7激动剂——咪喹莫特,能浓度依赖性地抑制TLR9激动剂引起的固有免疫反应。令人惊讶的是,这种抑制并非由TLR7介导,因为在TLR7的缺乏的情况下,TLR9激动剂导致的固有免疫反应仍然被抑制。固有免疫反应的抑制也并非由于抑制TLR9激动剂摄取所致。这提示咪喹莫特的抑制效应可能是直接作用,也许是通过阻滞CpG-ODN结合和/或TLR9介导的信号转导所致,从而限制细胞活化。这种拮抗关系也存在于小胶质细胞中的这2类受体之间,TLR7的缺乏导致CpG-ODN刺激的细胞因子反应增强。因此,在胶质细胞中,TLR7及其激动剂对TLR9介导的细胞因子反应有抑制作用。

关键词：大脑细胞因子共刺激咪喹莫特 CpG-ODN

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FoxJ1 inhibits African swine fever virus replication and viral S273R protein decreases the expression of FoxJ1 to impair its antiviral effect

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Virologica Sinica 2022年第3期37卷 445-454页

作者： Caina Ma Shasha Li Fan Yang Weijun Cao Huisheng Liu Tao Feng Keshan Zhang Zixiang Zhu Xiangtao Liu Yonghao Hu Haixue Zheng College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China State Key laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China

African swine fever(ASF)is a highly pathogenic swine infectious disease that affects domestic pigs and wild boar,which is caused by the African swine fever virus(ASFV).ASF has caused huge economic losses to the pig industry and seriously threatens global food security and livestock *** date,there is no safe and effective commercial vaccine against *** the underlying mechanisms of ASFV-host interplay is critical for developing effective vaccines and drugs against *** the present study,RNA-sequencing,RT-qPCR and Western blotting analysis revealed that the transcriptional and protein levels of the host factor FoxJ1 were significantly down-regulated in primary porcine alveolar macrophages(PAMs)infected by ***-qPCR analysis showed that overexpression of FoxJ1 upregulated the transcription of type I interferon and interferon stimulating genes(ISGs)induced by poly(dA:dT).FoxJ1 revealed a function to positively regulate innate immune response,therefore,suppressing the replication of *** addition,Western blotting analysis indicated that FoxJ1 degraded ASFV MGF505-2R and E165R proteins through autophagy ***,RT-qPCR and Western blotting analysis showed that ASFV S273R inhibited the expression of ***,we determined that FoxJ1 plays an antiviral role against ASFV replication,and ASFV protein impairs FoxJ1-mediated antiviral effect by degradation of *** findings provide new insights into the antiviral function of FoxJ1,which might help design antiviral drugs or vaccines against ASFV infection.

关键词： African swine fever virus(ASFV) FoxJ1 ISGs MGF505-2R E165R S273R

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