To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with ...To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment.Relevant data were collected regarding AILD diagnosis,treatment,biochemical indicators,and imaging examination.The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed.A total of 1,138 patients completed follow-up.The usage rate of hormone(P=0.003)and immunosuppressant(P=0.001)used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group.The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients(P=0.003).The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group(P=0.018).Logistic regression analysis showed that UDCA use(P=0.003)was correlated to a lower incidence of SARS-CoV-2,while immunosuppressant use(P=0.017)increased the incidence.Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group(P=0.018).UDCA is associated with low SARS-CoV-2 incidence in AILD patients,while immunosuppressant increases its incidence instead.Patients receiving UDCA treatment have a longer recovery time after being infected.展开更多
Autoimmune hepatitis(AIH)is a severe globally distributed liver disease that could occur at any age.Human menstrual blood-derived stem cells(MenSCs)have shown therapeutic effect in acute lung injury and liver failure....Autoimmune hepatitis(AIH)is a severe globally distributed liver disease that could occur at any age.Human menstrual blood-derived stem cells(MenSCs)have shown therapeutic effect in acute lung injury and liver failure.However,their role in the curative effect of AIH remains unclear.Here,a classic AIH mouse model was constructed through intravenous injection with concanavalin A(Con A).MenSCs were intravenously injected while Con A injection in the treatment groups.The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated.The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH,mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways.Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation,consistent with the TUNEL staining results.An AML12 co-culture system and JNK inhibitor(SP600125)were used to verify the JNK/MAPK and apoptosis signaling pathways.These findings suggested that MenSCs could be a promising strategy for AIH.展开更多
目的基于网络药理学和分子模拟对接技术探究苦黄颗粒治疗自身免疫性肝炎(autoimmune hepatitis,AIH)的活性成分和作用机制。方法通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and a...目的基于网络药理学和分子模拟对接技术探究苦黄颗粒治疗自身免疫性肝炎(autoimmune hepatitis,AIH)的活性成分和作用机制。方法通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)获取苦黄颗粒中5味药材的化学成分和作用靶点,并重新纳入药典标记的关键成分;通过PubChem数据库和String平台获得活性化合物的作用靶点,同时采用GeneCards和DisGeNET数据库获得AIH相关基因,两者取交集获得共有靶点,并经Cytoscape软件将结果可视化,通过网络拓扑算法获得核心化合物和核心靶点;通过String平台构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络获得苦黄颗粒治疗AIH的重要靶点,通过DAVID平台对重要靶点进行GO富集及京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析;使用Autodock Vina软件进行分子对接,验证网络分析结果。结果苦黄颗粒的主要活性成分84个,其中羽扇豆碱、梨果仙人掌基质以及槐胺碱等可能是苦黄颗粒治疗AIH的核心化合物。筛选出苦黄颗粒治疗AIH的7个核心靶点,即IL-6、IL-10、CXCL8、IL-4、ICAM1、HMOX1和IL-2。GO功能富集分析和KEGG通路富集分析显示,苦黄颗粒主要对细胞凋亡进程、炎症反应以及机体免疫等生物过程进程调控。结论苦黄颗粒可通过多组分-多靶点-多通路调控机体炎症,调节免疫反应,从而发挥治疗AIH的作用,其中7个主要核心靶点可能为苦黄颗粒发挥作用的关键靶点,TNF信号通路、T细胞受体信号通路及Toll样受体信号通路可能是苦黄颗粒参与调控机体炎症和免疫的关键信号通路,可成为后续探究苦黄颗粒治疗AIH作用机制的潜在研究方向。展开更多
基金the National Key Research and Development Program(2022YFC2603500,2022YFC2603505)Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26,Beijing Hospitals Authority Clinical medicine Development of special funding support(XMLX 202127)+1 种基金the capital health research and development of special public health project(2022-1-2172)The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302).
文摘To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment.Relevant data were collected regarding AILD diagnosis,treatment,biochemical indicators,and imaging examination.The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed.A total of 1,138 patients completed follow-up.The usage rate of hormone(P=0.003)and immunosuppressant(P=0.001)used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group.The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients(P=0.003).The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group(P=0.018).Logistic regression analysis showed that UDCA use(P=0.003)was correlated to a lower incidence of SARS-CoV-2,while immunosuppressant use(P=0.017)increased the incidence.Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group(P=0.018).UDCA is associated with low SARS-CoV-2 incidence in AILD patients,while immunosuppressant increases its incidence instead.Patients receiving UDCA treatment have a longer recovery time after being infected.
基金supported by Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.81721091)The Independent Task of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine。
文摘Autoimmune hepatitis(AIH)is a severe globally distributed liver disease that could occur at any age.Human menstrual blood-derived stem cells(MenSCs)have shown therapeutic effect in acute lung injury and liver failure.However,their role in the curative effect of AIH remains unclear.Here,a classic AIH mouse model was constructed through intravenous injection with concanavalin A(Con A).MenSCs were intravenously injected while Con A injection in the treatment groups.The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated.The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH,mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways.Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation,consistent with the TUNEL staining results.An AML12 co-culture system and JNK inhibitor(SP600125)were used to verify the JNK/MAPK and apoptosis signaling pathways.These findings suggested that MenSCs could be a promising strategy for AIH.
文摘目的基于网络药理学和分子模拟对接技术探究苦黄颗粒治疗自身免疫性肝炎(autoimmune hepatitis,AIH)的活性成分和作用机制。方法通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)获取苦黄颗粒中5味药材的化学成分和作用靶点,并重新纳入药典标记的关键成分;通过PubChem数据库和String平台获得活性化合物的作用靶点,同时采用GeneCards和DisGeNET数据库获得AIH相关基因,两者取交集获得共有靶点,并经Cytoscape软件将结果可视化,通过网络拓扑算法获得核心化合物和核心靶点;通过String平台构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络获得苦黄颗粒治疗AIH的重要靶点,通过DAVID平台对重要靶点进行GO富集及京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析;使用Autodock Vina软件进行分子对接,验证网络分析结果。结果苦黄颗粒的主要活性成分84个,其中羽扇豆碱、梨果仙人掌基质以及槐胺碱等可能是苦黄颗粒治疗AIH的核心化合物。筛选出苦黄颗粒治疗AIH的7个核心靶点,即IL-6、IL-10、CXCL8、IL-4、ICAM1、HMOX1和IL-2。GO功能富集分析和KEGG通路富集分析显示,苦黄颗粒主要对细胞凋亡进程、炎症反应以及机体免疫等生物过程进程调控。结论苦黄颗粒可通过多组分-多靶点-多通路调控机体炎症,调节免疫反应,从而发挥治疗AIH的作用,其中7个主要核心靶点可能为苦黄颗粒发挥作用的关键靶点,TNF信号通路、T细胞受体信号通路及Toll样受体信号通路可能是苦黄颗粒参与调控机体炎症和免疫的关键信号通路,可成为后续探究苦黄颗粒治疗AIH作用机制的潜在研究方向。
