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Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation

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Journal of Pharmaceutical Analysis 2023年第1期13卷 11-23页

作者： Ningning Wang Entao Li Huifang Deng Lanxin Yue Lei Zhou Rina Su Baokun He chengcai lai Gaofu Li Yuwei Gao Wei Zhou Yue Gao Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing100850China Tianjin University of Traditional Chinese Medicine Tianjin301617China Changchun Veterinary Research Institute Chinese Academy of Agricultural SciencesChangchun130122China College of Veterinary Medicine Jilin Agricultural UniversityChangchun130022China Department of Gastroenterology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai200080China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and *** and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical ***,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this *** found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by multiple infectious *** significantly improved survival in mice infected with *** indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear translocation of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopolysaccharide(LPS),H1N1,or ***,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical ***,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

关键词： Cytokine stormInterleukin 6 (IL-6)InosineSARS-CoV-2TANK-binding kinase 1 (TBK1)

吴茱萸肝毒性机制的阐明——基于QSAR毒性预测和代谢组学研究

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Acupuncture and Herbal Medicine 2024年第2期4卷 257-270,I0013,I0014页

作者：杨春启赖成材茹毅沈宝英吴香军崔佳露李方杨张程师卓钱庆元肖成荣王宇光张伯礼高月北京工业大学环境与生命学部北京军事医学研究院辐射医学研究所北京天津中医药大学组分中药国家重点实验室天津不详

[目的]吴茱萸是临床上治疗胃肠道疾病的中药,已被广泛应用。然而,吴茱萸在《中国药典》及本草著作中被认为是一种“小毒”的中药。本研究采用毒性预测与体内外研究相结合的方法,鉴定吴茱萸的毒性成分和毒性靶器官,并从代谢角度探讨其毒... 详细信息

[目的]吴茱萸是临床上治疗胃肠道疾病的中药,已被广泛应用。然而,吴茱萸在《中国药典》及本草著作中被认为是一种“小毒”的中药。本研究采用毒性预测与体内外研究相结合的方法,鉴定吴茱萸的毒性成分和毒性靶器官,并从代谢角度探讨其毒性机制。[方法]通过体外和体内研究,对吴茱萸的毒性靶器官进行鉴定。通过生物碱富集和分离进行体外毒性筛选。基于定量构效关系(QSAR)构建,通过吸收、分布、代谢、排泄和毒性预测因子(ADMET Prodictor)预测化合物的潜在毒性。此外,研究整合了服用潜在毒性成分后的血清代谢组学分析,以阐明潜在毒性物质对小鼠代谢的影响。[结果]比较不同提取方法及炮制前后对小鼠的急性毒性,吴茱萸醇提物毒性最高,吴茱萸毒性的靶器官为肝脏。吴茱萸醇提物的生物碱组分具有较强的细胞毒性。ADMET Predictor对吴茱萸的潜在毒性进行了计算和预测,认为生物碱是导致吴茱萸毒性的主要原因。而吴茱萸碱在体外显著减少细胞数量,提高线粒体膜电位。吴茱萸碱给药后,小鼠血清代谢组学对不同的代谢产物进行了显著鉴定,其中胆汁酸代谢和类固醇激素生物合成是肝毒性的关键途径。[结论]通过比较不同提取方法在加工前后的急性毒性,阐明吴茱萸炮制品临床应用的科学意义。将基于QSAR的毒性预测与体内外毒性筛选相结合,可以鉴定吴茱萸的潜在毒性靶器官和毒性成分。通过代谢组学研究,初步揭示吴茱萸的肝毒性可能与胆汁酸代谢和类固醇激素生物合成有关。本研究为阐明吴茱萸的作用机理、评价其安全性和质量奠定了基础。

关键词： ADMET Prodictor 吴茱萸吴茱萸碱肝毒性 LD50 代谢组学

Angiotensin-converting enzyme 2(ACE2) mediates influenza H7N9 virus-induced acute lung injury

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Angiotensin-converting enzyme 2(ACE2) mediates influenza H7N...

第十届全国免疫学学术大会

作者： Penghui Yang Hongjing Gu chengcai lai Shaogeng Zhang Xiliang Wang Beijing302 Hospital State Key Laboratory of Pathogens and Biosecurity Beijing Institute of Microbiology and Epidemiology

Since 2013,the emergence of an avian-origin influenza A(H7N9)virus has raised concern in *** most infections resulted in respiratory illness,some severe cases resulted in acute respiratory distress syndrome(ARDS),which is a severe form of acute lung injury(ALI)that further contributes to *** date,no effective drugs that improve the clinical outcome of influenza A(H7N9)virus-infected patients have been ***-converting

关键词： H7N9 influenza ACE2 lung injury

Basic fibroblast growth factor protects against influenza A virus-induced acute lung injury by recruiting neutrophils

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Journal of Molecular Cell Biology 2018年第6期10卷 573-585页

作者： Keyu Wang chengcai lai Tieling Li Cheng Wang Wei Wang Bing Ni Changqing Bai Shaogeng Zhang Lina Han Hongjing Gu Zhongpeng Zhao Yueqiang Duan Xiaolan Yang Li Xing Lingna Zhao Shanshan Zhou Min Xia Chengyu Jiang Xiliang Wang Penghui Yang State Key Laboratory of Pathogens and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Chinese PLA General Hospital Beijing 100853China State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology Third Military Medical UniversityChongqing 400038China Beijing 307 Hospital of PLA Affiliated with the Chinese Academy of Medical Sciences Beijing 100070China Beijing 302 Hospital of PLA Beijing 100039China

Influenza virus (IAV)infection is a major cause of severe respiratory illness that affects almost every country in the *** infections result in respiratory illness and even acute lung injury and death,but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully *** this study,the basic fibroblast growth factor 2 (FGF2)level was markedly increased in H1N1 virus-infected humans and ***2,which is predominately derived from epithelial cells,recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFKB signaling ***2 depletion or knockout exacerbated influenzaassociated disease by impairing neutrophil recruitment and *** importantly,administration of the recombinant FGF2 protein significantly aUeviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected *** on the results from experiments in which neutrophils were depleted and adoptively transferred,FGF2 protected mice against IAV , infection by recruiting ***,FGF2 plays a critical role in preventing IAV-induced lung injury,and FGF2 is a promising potential therapeutic target during IAV infection.

关键词： influenza H1N1 virus recombinant FGF2 protein neutrophil recruitment FGFR2-PI3K-AKT-NFκB signaling therapeutic target

Angiotensin-converting enzyme 2 plays a crucial role in respiratory syncytial virus-induced lung injury

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Angiotensin-converting enzyme 2 plays a crucial role in resp...

第十届全国免疫学学术大会

作者： Hongjing Gu Ping Zhu chengcai lai Keyu Wang zhongpeng Zhao Penghui Yang Xiliang Wang Beijing Institute of Microbiology and Epidemiology 302 hospital

Respiratory syncytial virus(RSV)infection is the major cause of severe lower respiratory illness in infants and young children,but the underlying mechanisms responsible for the pathogenesis are not fully *** date,no drugs or vaccines have been employed to improve the clinical outcome of RSV-infected *** this study,we report that angiotensin-converting enzyme-2(ACE2)protects against the severe lung injury induced by RSV infection in an experimental mouse model and in pediatric ***,ACE2 deficiency aggravates the disease pathogenesis,mainly by targeting the angiotensin II type 1 receptor(AT1 R).Furthermore,recombinant ACE2 protein alleviates the severity of RSV-induced lung *** findings demonstrate that ACE2 plays a critical role in RSV-induced lung injury,and suggest that ACE2 is a promising potential therapeutic target for RSV-induced lung disease.

关键词： RSV ACE2 Lung injury

Long non-coding RNA RP11J20.1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis

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Long non-coding RNA RP11J20.1 predicts a poor prognosis and ...

第十一届全国免疫学学术大会

作者： Penghui Yang Sijie Cheng chengcai lai Jin Yan Peirui Zhang Shaogeng Zhang Xiliang Wang Beijing 302 Hospital Beijing Institute of Microbiology and Epidemiology State Key Laboratory of Pathogen and Biosecurity

Hepatocellular carcinoma(HCC) is a leading cause of cancer mortality worldwide. Despite progress in the diagnosis and treatment of HCC, its prognosis still remains unfavorable. In accumulating studies, long non-coding RNAs(lncRNAs) are emerging as vital players in tumorigenesis and cancer progression. However, the molecular mechanisms and clinical significance of lncRNAs in HCC remain largely elusive. In this study, we analyzed lncRNA microarray expressionprofiles of tumor samples and its matched adjacent tissue samples from 10 HCC patients and found that the expression of RP11J20.1 in HCC tissues is makedly lower than adjacent tissues. Expression of RP11J20.1 was also remarkably downregulated in 112 HCC tissues and cell lines by qRT-PCR. Low RP11J20.1 expression was correlated with alphafetoprotein(AFP) level, tumor size and microvascular invasion. Kaplan-Meier survival analysis demonstrated that low RP11J20.1 expression predicts poor prognosis of HCC patients. Gain-of-function and loss-of-function experiments showed that RP11J20.1 promotes HCC cells proliferation, cell cycle progression, and inhibits HCC cells apoptosis. Further experiments revealed that RP11J20.1 promotes HCC cells proliferation through inhibiting STAT1 genes expression. Collectively, our results demonstrated the clinical prognostic significance and roles of RP11J20.1 in HCC, and suggested that RP11J20.1 may be considered as a prognostic biomarker and therapeutic target for HCC.

关键词： lncRNA hepatocellular carcinoma RP11J20 1 qRT-PCR

Bivalent vaccine platform based on influenza virus elicits protective immune response against FLU and hepatitis C virus

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Bivalent vaccine platform based on influenza virus elicits p...

第十一届全国免疫学学术大会

作者： Penghui Yang Tianyu Ren Fang Sun Hongjing Gu chengcai lai Shaogeng Zhang Xiliang Wang Beijing 302 Hospital Beijing Institute of Microbiology and Epidemiology State Key Laboratory of Pathogen and Biosecurity

Hepatitis C virus(HCV)has the devastating impact of endanger human health,which can evolve into liver fibrosis,cirrhosis as well as hepatocellular *** now,an effective HCV vaccine is not *** this study,we generated a recombinant PR8 influenza virus vector carrying the core and envelope glycoproteins(C/E1/E2)epitopes of HCV inserted into the influenza nonstructural(NS1)protein gene,termed as ***

关键词： Influenza virus HCV Hexon protein epitopes viral vector

Basic fibroblast growth factor(FGF2) plays a crucial role in influenza A virus-induced acute lung injury

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Basic fibroblast growth factor(FGF2) plays a crucial role in...

第十一届全国免疫学学术大会

作者： Wang Keyu lai chengcai Gu Hongjing Zhao Zhongpeng Duan Yueqiang Yang Xiaolan Yang Penghui Wang Xiliang State Key Laboratory of Pathogens and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing 302 Hospital of PLA

Influenza virus(IFV) infection is a major cause of severe respiratory illness that affects almost every country in the world. IFV infections result in respiratory illness and even acute lung injury and death, but the underlying mechanisms responsible for IFV pathogenesis remain to be fully elucidated. In this study, we found that the basic fibroblast growth factor 2(FGF2) level was markedly increased in H1N1 virus-infected humans and mice. FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFκB signaling pathway. FGF2 depletion or knockoutexacerbated influenza-associated disease by impairing neutrophil recruitment and activation. More importantly, administration of recombinant FGF2 protein significantly alleviated the severity of IFV-induced lunginjury and promotedthe survival of IFV-infected animals. These findings demonstrate that FGF2 plays a critical role in preventing IFV-induced lung injury and suggest FGF2 as a promising potential therapeutic target during IFV infection.

关键词： H1N1 FGF2 neutrophils NFκB signaling therapy

Long noncoding RNA AVAN mediates antiviral innate immune response via enhance the deubiquitination of TRIM25 and expression of FOXO3a

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Long noncoding RNA AVAN mediates antiviral innate immune res...

第十二届全国免疫学学术大会

作者： lai chengcai Wang Keyu Gu Hongjing Zhao Lingna Zhou Shanshan Xia Min Yang Penghui Xiliang Wang Beijing Institute of Microbiology and Epidemiology State Key Laboratory of Pathogen and Biosecurity Beijing 302 Hospital of PLA

Long noncoding RNAs(IncRNAs)regulate a number of biological process and immune ***,the role of IncRNAs in innate immune responses remained largely ***,we indentified a uncharacterized

关键词： long noncoding RNA AVAN virus TRIM25 FOX03a