SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the ass...SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.展开更多
Background:Recent studies have shown that mediator complex subunit 1(Med1)can significantly affect hepatocyte proliferation and differentiation.Acting as a tumor suppressor,microRNA-637(hsa-miR-637)can inhibit the gro...Background:Recent studies have shown that mediator complex subunit 1(Med1)can significantly affect hepatocyte proliferation and differentiation.Acting as a tumor suppressor,microRNA-637(hsa-miR-637)can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis.However,the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated.Methods:This study used co-immunoprecipitation(Co-IP)assay,transfection,luciferase reporter assay,functional assay by cell counting kit-8(CCK-8),Annexin V-FITC/propidium iodide apoptosis assay,and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation(ChIP)for analysis.Results:Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors,identified as the peroxisome proliferator-activated receptor alpha(PPARA)and thyroid hormone receptor alpha(THRA)at the transcriptional and translational levels in the human liver HL-7702 cell line.The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed.The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated.Moreover,hsamiR-637 has been determined to suppress the proliferation of HL-7702 cells.Furthermore,cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase,but its apoptosis failed.Finally,PPARA was indicated to directly bind to the promoter of some transcription factors,like bcatenin,mouse double minute 2(MDM2),and p53.Conclusions:This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration,which may contribute in understanding the regenerative process of the liver.展开更多
基金supported by National Science and Technology Major Project(2018ZX10302204)Shenzhen Science and Technology Program(Grant No.KQTD20200820145822023)+3 种基金Emergency special program for 2019-nCov of Guangdong province science and technology project(2020B111105001)Guangzhou science and technology project(202008040003)Clinical Research Foundation of the third Affiliated Hospital of Sun Yat-sen University(YHJH201904)National Natural Science Foundation of China(Grant No.31900056).
文摘SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.
基金This study was supported by the National Science and Technology Major Project of China(2018ZX10302204-002)The authors would like to thank BersinBio(Guangzhou,China)for their technical assistance.
文摘Background:Recent studies have shown that mediator complex subunit 1(Med1)can significantly affect hepatocyte proliferation and differentiation.Acting as a tumor suppressor,microRNA-637(hsa-miR-637)can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis.However,the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated.Methods:This study used co-immunoprecipitation(Co-IP)assay,transfection,luciferase reporter assay,functional assay by cell counting kit-8(CCK-8),Annexin V-FITC/propidium iodide apoptosis assay,and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation(ChIP)for analysis.Results:Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors,identified as the peroxisome proliferator-activated receptor alpha(PPARA)and thyroid hormone receptor alpha(THRA)at the transcriptional and translational levels in the human liver HL-7702 cell line.The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed.The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated.Moreover,hsamiR-637 has been determined to suppress the proliferation of HL-7702 cells.Furthermore,cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase,but its apoptosis failed.Finally,PPARA was indicated to directly bind to the promoter of some transcription factors,like bcatenin,mouse double minute 2(MDM2),and p53.Conclusions:This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration,which may contribute in understanding the regenerative process of the liver.