Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cogniti...Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cognitive.The etiology of SCZ is thought to be multifactorial and poorly understood.Accumulating evidence has indicated abnormal synaptic plasticity and cognitive impairments in SCZ.Synaptic plasticity is thought to be induced at appropriate synapses during memory formation and has a critical role in the cognitive symptoms of SCZ.Many factors,including synaptic structure changes,aberrant expression of plasticityrelated genes,and abnormal synaptic transmission,may influence synaptic plasticity and play vital roles in SCZ.In this article,we briefly summarize the morphology of the synapse,the neurobiology of synaptic plasticity,and the role of synaptic plasticity,and review potential mechanisms underlying abnormal synaptic plasticity in SCZ.These abnormalities involve dendritic spines,postsynaptic density,and long-term potentiation-like plasticity.We also focus on cognitive dysfunction,which reflects impaired connectivity in SCZ.Additionally,the potential targets for the treatment of SCZ are discussed in this article.Therefore,understanding abnormal synaptic plasticity and impaired cognition in SCZ has an essential role in drug therapy.展开更多
Dear Editor,Alternative splicing of eukaryotic transcripts refers to the posttranscriptional process in which the coding regions(exons)of a precursor transcript are joined in different combinations through the removal...Dear Editor,Alternative splicing of eukaryotic transcripts refers to the posttranscriptional process in which the coding regions(exons)of a precursor transcript are joined in different combinations through the removal or retention of non-coding intervening sequences(introns)to produce distinct mature messenger RNA(mRNA)transcripts and further generate one or more mature mRNAs(Lee and Rio,2015).Alternative splicing is revealed dysregulation in infectious diseases.Many pathogens hijack the splicing mechanism of host cells to complete their replications,accompanied by dysregulated innate immune response or cell damage,leading to the changes of alternative splicing landscape in host cells(Ashraf et al.,2019;Tomezsko et al.,2020;Kremsdorf et al.,2021).The regulation mechanism of alternative splicing by viral pathogens,such as hepatitis B virus(Duriez et al.,2017),human immunodeficiency virus 1(Tomezsko et al.,2020),Zika virus(Bonenfant et al.,2020)and enterovirus 71(Li et al.,2020),have been explored.展开更多
Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection routine.Despite the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV i...Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection routine.Despite the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV is associated with more severe forms of liver diseases.However,the complexity of viral interference and underlying pathological mechanism is still unclarified.With the demonstration of absence of direct viral interplay,some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance outcome.Here,we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR mice.We found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order,while HBV did not affect HCV replication.Pathological alteration was coincidently reproduced in coinfected mice.In addition to the participation of innate immune response,an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV clearance.Our systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection,which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.展开更多
It is estimated that more than 300 million people in China are suffering from different liver diseases including viral hepatitis,fatty liver,alcoholic liver,liver fibrosis,cirrhosis and liver cancer,of which about 400...It is estimated that more than 300 million people in China are suffering from different liver diseases including viral hepatitis,fatty liver,alcoholic liver,liver fibrosis,cirrhosis and liver cancer,of which about 400,000 people die each year[1].The clinical resolution of these diseases relies largely on the breakthroughs from basic research.Human primary hepatocytes(PHHs)have long been considered as the"gold standard"for in vitro liver disease research models.However,there are still a number of limitations,like high donor variability,short life spans and limited availability.展开更多
Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on H...Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.展开更多
Hepatitis B virus(HBV),which was discovered in 1965,is a threat to global public health.HBV infects human hepatocytes and leads to acute and chronic liver diseases,and there is no cure.In cells infected by HBV,viral D...Hepatitis B virus(HBV),which was discovered in 1965,is a threat to global public health.HBV infects human hepatocytes and leads to acute and chronic liver diseases,and there is no cure.In cells infected by HBV,viral DNA can be integrated into the cellular genome.HBV DNA integration is a complicated process during the HBV life cycle.Although HBV integration normally results in replication-incompetent transcripts,it can still act as a template for viral protein expression.Of note,it is a primary driver of hepatocellular carcinoma(HCC).Recently,with the development of detection methods and research models,the molecular biology and the pathogenicity of HBV DNA integration have been better revealed.Here,we review the advances in the research of HBV DNA integration,including molecular mechanisms,detection methods,research models,the effects on host and viral gene expression,the role of HBV integrations in the pathogenesis of HCC,and potential treatment strategies.Finally,we discuss possible future research prospects of HBV DNA integration.展开更多
基金Supported by National Natural Science Foundation of China,No. 81971943, No. 81772196, No. 31470264, No. 81271820, No. 30870789 and No. 30300117Stanley Foundation from the Stanley Medical Research Institute (SMRI),United States,No. 06R-1366 (to Dr. Zhu F)Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University,No. TFJC 2018002
文摘Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cognitive.The etiology of SCZ is thought to be multifactorial and poorly understood.Accumulating evidence has indicated abnormal synaptic plasticity and cognitive impairments in SCZ.Synaptic plasticity is thought to be induced at appropriate synapses during memory formation and has a critical role in the cognitive symptoms of SCZ.Many factors,including synaptic structure changes,aberrant expression of plasticityrelated genes,and abnormal synaptic transmission,may influence synaptic plasticity and play vital roles in SCZ.In this article,we briefly summarize the morphology of the synapse,the neurobiology of synaptic plasticity,and the role of synaptic plasticity,and review potential mechanisms underlying abnormal synaptic plasticity in SCZ.These abnormalities involve dendritic spines,postsynaptic density,and long-term potentiation-like plasticity.We also focus on cognitive dysfunction,which reflects impaired connectivity in SCZ.Additionally,the potential targets for the treatment of SCZ are discussed in this article.Therefore,understanding abnormal synaptic plasticity and impaired cognition in SCZ has an essential role in drug therapy.
基金supported by the National Key Research and Development Plan of China(Grant No.2021YFC2300700).
文摘Dear Editor,Alternative splicing of eukaryotic transcripts refers to the posttranscriptional process in which the coding regions(exons)of a precursor transcript are joined in different combinations through the removal or retention of non-coding intervening sequences(introns)to produce distinct mature messenger RNA(mRNA)transcripts and further generate one or more mature mRNAs(Lee and Rio,2015).Alternative splicing is revealed dysregulation in infectious diseases.Many pathogens hijack the splicing mechanism of host cells to complete their replications,accompanied by dysregulated innate immune response or cell damage,leading to the changes of alternative splicing landscape in host cells(Ashraf et al.,2019;Tomezsko et al.,2020;Kremsdorf et al.,2021).The regulation mechanism of alternative splicing by viral pathogens,such as hepatitis B virus(Duriez et al.,2017),human immunodeficiency virus 1(Tomezsko et al.,2020),Zika virus(Bonenfant et al.,2020)and enterovirus 71(Li et al.,2020),have been explored.
基金supported by National Key Research and Development Program of China(2018YFA0507201 to X.C)the grants from the National Natural Science Foundation of China(81672021 to R.P,31770180 to C.W)。
文摘Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection routine.Despite the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV is associated with more severe forms of liver diseases.However,the complexity of viral interference and underlying pathological mechanism is still unclarified.With the demonstration of absence of direct viral interplay,some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance outcome.Here,we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR mice.We found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order,while HBV did not affect HCV replication.Pathological alteration was coincidently reproduced in coinfected mice.In addition to the participation of innate immune response,an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV clearance.Our systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection,which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.
文摘It is estimated that more than 300 million people in China are suffering from different liver diseases including viral hepatitis,fatty liver,alcoholic liver,liver fibrosis,cirrhosis and liver cancer,of which about 400,000 people die each year[1].The clinical resolution of these diseases relies largely on the breakthroughs from basic research.Human primary hepatocytes(PHHs)have long been considered as the"gold standard"for in vitro liver disease research models.However,there are still a number of limitations,like high donor variability,short life spans and limited availability.
基金the National Natural Science Foundation of China(project no.81971936)Hubei Province's Outstanding Medical Academic Leader Program,Foundation for Innovative Research Groups of the Natural Science Foundation of Hubei(project no.2020CFA015)the Funda-mental Research Funds for the Central Universities(project no.2042022kf1215 and 2042021gf0013)and Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital,Wuhan University.
文摘Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.
基金This work was supported by the National Natural Science Foundation of China(project no.82041004)the Fundamental Research Funds for the Central Universities and Gilead Sciences Research Scholars Program in Liver Disease Asia.
文摘Hepatitis B virus(HBV),which was discovered in 1965,is a threat to global public health.HBV infects human hepatocytes and leads to acute and chronic liver diseases,and there is no cure.In cells infected by HBV,viral DNA can be integrated into the cellular genome.HBV DNA integration is a complicated process during the HBV life cycle.Although HBV integration normally results in replication-incompetent transcripts,it can still act as a template for viral protein expression.Of note,it is a primary driver of hepatocellular carcinoma(HCC).Recently,with the development of detection methods and research models,the molecular biology and the pathogenicity of HBV DNA integration have been better revealed.Here,we review the advances in the research of HBV DNA integration,including molecular mechanisms,detection methods,research models,the effects on host and viral gene expression,the role of HBV integrations in the pathogenesis of HCC,and potential treatment strategies.Finally,we discuss possible future research prospects of HBV DNA integration.