There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progre...There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.展开更多
Colorectal cancer(CRC)is a common malignant tumor that affects people worldwide.Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F.nucleatum)in colorectal carcinoma tissue;many studies have ind...Colorectal cancer(CRC)is a common malignant tumor that affects people worldwide.Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F.nucleatum)in colorectal carcinoma tissue;many studies have indicated that F.nucleatum is closely related to the colorectal carcinogenesis.In this review,we provide the latest information to reveal the related molecular mechanisms.The known virulence factors of F.nucleatum promote adhesion to intestinal epithelial cells via FadA and Fap2.Besides,Fap2 also binds to immune cells causing immunosuppression.Furthermore,F.nucleatum recruits tumor-infiltrating immune cells,thus yielding a pro-inflammatory microenvironment,which promotes colorectal neoplasia progression.F.nucleatum was also found to potentiate CRC development through toll-like receptor 2(TLR2)/toll-like receptor 4(TLR4)signaling and microRNA(miRNA)-21 expression.In addition,F.nucleatum increases CRC recurrence along with chemoresistance by mediating a molecular network of miRNA-18a*,miRNA-4802,and autophagy components.Moreover,viable F.nucleatum was detected in mouse xenografts of human primary colorectal adenocarcinomas through successive passages.These findings indicated that an increased number o f F.nucleatum in the tissues is a biomarker for the diagnosis and prognosis of CRC,and the underlying molecular mechanism can probably provide a potential intervention treatment strategy for patients with F.nucleatum-associaied CRC.展开更多
Current cancer therapies have encountered adverse response due to poor therapeutic efficiency,severe side effects and acquired resistance to multiple drugs.Thus,there are urgent needs for finding new cancer-targeted p...Current cancer therapies have encountered adverse response due to poor therapeutic efficiency,severe side effects and acquired resistance to multiple drugs.Thus,there are urgent needs for finding new cancer-targeted pharmacological strategies.In this review,we summarized the current understanding with THZ1,a covalent inhibitor of cyclin-dependent kinase 7(CDK7),which demonstrated promising anti-tumor activity against different cancer types.By introducing the anti-tumor behaviors and the potential targets for different cancers,this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms.展开更多
文摘There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.
文摘Colorectal cancer(CRC)is a common malignant tumor that affects people worldwide.Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F.nucleatum)in colorectal carcinoma tissue;many studies have indicated that F.nucleatum is closely related to the colorectal carcinogenesis.In this review,we provide the latest information to reveal the related molecular mechanisms.The known virulence factors of F.nucleatum promote adhesion to intestinal epithelial cells via FadA and Fap2.Besides,Fap2 also binds to immune cells causing immunosuppression.Furthermore,F.nucleatum recruits tumor-infiltrating immune cells,thus yielding a pro-inflammatory microenvironment,which promotes colorectal neoplasia progression.F.nucleatum was also found to potentiate CRC development through toll-like receptor 2(TLR2)/toll-like receptor 4(TLR4)signaling and microRNA(miRNA)-21 expression.In addition,F.nucleatum increases CRC recurrence along with chemoresistance by mediating a molecular network of miRNA-18a*,miRNA-4802,and autophagy components.Moreover,viable F.nucleatum was detected in mouse xenografts of human primary colorectal adenocarcinomas through successive passages.These findings indicated that an increased number o f F.nucleatum in the tissues is a biomarker for the diagnosis and prognosis of CRC,and the underlying molecular mechanism can probably provide a potential intervention treatment strategy for patients with F.nucleatum-associaied CRC.
文摘Current cancer therapies have encountered adverse response due to poor therapeutic efficiency,severe side effects and acquired resistance to multiple drugs.Thus,there are urgent needs for finding new cancer-targeted pharmacological strategies.In this review,we summarized the current understanding with THZ1,a covalent inhibitor of cyclin-dependent kinase 7(CDK7),which demonstrated promising anti-tumor activity against different cancer types.By introducing the anti-tumor behaviors and the potential targets for different cancers,this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms.
