Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that gene...Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.展开更多
Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon...Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.展开更多
Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,i...Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,including vulner-ability to viral infections,inflammation,and cancer progression.In particular,the interplay between lung adenocarcinoma(LUAD)and viral infections appears to exist in association with the deregulation of IFN-γsignaling.In this mini-review,we investigated the status of the IFN-γsignaling pathway and the expression level of its components in LUAD.Interestingly,a reduction in IFNGR1 expression seems to be associated with LUAD progression,affecting defenses against viruses such as severe acute respiratory syndrome coronavirus 2.In addition,alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-γsignaling in LUAD.展开更多
基金supported by the National Natural Science Foundation Council of China(82172386 and 81922081 to C.L.,82100943 to X.F.,82104216 to J.L.,and 82230081,82250710175 and 8226116039 to G.X.)the Department of Education of Guangdong Province(2021KTSCX104 to C.L.)+5 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.)the Guangdong Provincial Science and Technology Innovation Council Grant(2017B030301018 to G.X.)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.,and 2023A1515012000 to X.F.)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.,JCYJ20220530115006014 to X.F.,JCYJ20230807095118035 to J.L.,and JCYJ20220818100617036 to G.X.)the Hong Kong General Research Fund(12102722 to A.L.)the Hong Kong RGC Themebased Research Scheme(T12-201/20-R to A.L.).
文摘Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.
基金the research council of Kerman University of Medical Sciences,Kerman,Iran(Grant Number:400000232).
文摘Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.
文摘Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,including vulner-ability to viral infections,inflammation,and cancer progression.In particular,the interplay between lung adenocarcinoma(LUAD)and viral infections appears to exist in association with the deregulation of IFN-γsignaling.In this mini-review,we investigated the status of the IFN-γsignaling pathway and the expression level of its components in LUAD.Interestingly,a reduction in IFNGR1 expression seems to be associated with LUAD progression,affecting defenses against viruses such as severe acute respiratory syndrome coronavirus 2.In addition,alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-γsignaling in LUAD.