Patients with brain tumors,specifically,malignant forms such as glioblastoma,medulloblastoma and ependymoma,exhibit dismal survival rates despite advances in treatment strategies.Chemotherapeutics,the primary adjuvant...Patients with brain tumors,specifically,malignant forms such as glioblastoma,medulloblastoma and ependymoma,exhibit dismal survival rates despite advances in treatment strategies.Chemotherapeutics,the primary adjuvant treatment for human brain tumors following surgery,commonly lack efficacy due to either intrinsic or acquired drug resistance.New treatments targeting epigenetic factors are being explored.Post-translational histone modification provides a critical regulatory platform for processes such as chromosome condensation and segregation,apoptosis,gene transcription,and DNA replication and repair.This work reviews how aberrant histone modifications and alterations in histone-modifying enzymes can drive the acquisition of drug resistance in brain tumors.Elucidating these mechanisms should lead to new treatments for overcoming drug resistance.展开更多
Precise and dynamic regulation of gene expression is a key feature of immunity.In recent years,rapid advances in transcriptome profiling analysis have led to recognize long noncoding RNAs(lncRNAs)as an additional laye...Precise and dynamic regulation of gene expression is a key feature of immunity.In recent years,rapid advances in transcriptome profiling analysis have led to recognize long noncoding RNAs(lncRNAs)as an additional layer of gene regulation context.In the immune system,lncRNAs are found to be widely expressed in immune cells including monocytes,macrophages,dendritic cells(DC),neutrophils,T cells and B cells during their development,differentiation and activation.However,the functional importance of immune-related lncRNAs is just emerging to be characterized.In this review,we discuss the up-to-date knowledge of lncRNAs in immune regulation.展开更多
Macrophages are dominant innate immune cells.They demonstrate remarkable het-erogeneity and plasticity that are essential for homeostasis and host defense.The heterogeneity of tissue macrophages is shaped by the ontog...Macrophages are dominant innate immune cells.They demonstrate remarkable het-erogeneity and plasticity that are essential for homeostasis and host defense.The heterogeneity of tissue macrophages is shaped by the ontogeny,tissue factors,and environmental signals,a pattern in a tissue-associated latitudinal manner.At the same time,macrophages have long been considered as mainly plastic cells.These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation,including coordination of signal trans-ducer,epigenetic elements,and transcription factors,conclusively determine the macrophage phenotypes and functions.With the development of cutting-edge technologies,such as fate-mapping,single-cell transcriptomics,ipsc platform,nanotherapeutic materials,etc.,our under-standing of macrophage biology and the roles in the pathogenesis of diseases is much advanced.This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases.The latitudinal regulation covers the tissue macrophage or-igins,tissue factors,and environmental signals,reflecting the macrophage heterogeneity.The lon-gitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases(i.e.,inflammatory bowel disease).In addition,how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.展开更多
基金Supported by the Rory David Deutsch Foundationthe Surgical Neuro-oncology Research Fund of Ann&Robert H Lurie Children’s Hospital(A&RLCH) of Chicagothe Dr.Ralph and Marian C.Falk Medical Research Trust
文摘Patients with brain tumors,specifically,malignant forms such as glioblastoma,medulloblastoma and ependymoma,exhibit dismal survival rates despite advances in treatment strategies.Chemotherapeutics,the primary adjuvant treatment for human brain tumors following surgery,commonly lack efficacy due to either intrinsic or acquired drug resistance.New treatments targeting epigenetic factors are being explored.Post-translational histone modification provides a critical regulatory platform for processes such as chromosome condensation and segregation,apoptosis,gene transcription,and DNA replication and repair.This work reviews how aberrant histone modifications and alterations in histone-modifying enzymes can drive the acquisition of drug resistance in brain tumors.Elucidating these mechanisms should lead to new treatments for overcoming drug resistance.
基金This work was supported in part by the grants including R01DK064240(to XDT)and R21AA020494(to XDT)National Institutes of Health and Merit Review Award(I01BX001690 to XDT)from US Department of Veterans Affairs.
文摘Precise and dynamic regulation of gene expression is a key feature of immunity.In recent years,rapid advances in transcriptome profiling analysis have led to recognize long noncoding RNAs(lncRNAs)as an additional layer of gene regulation context.In the immune system,lncRNAs are found to be widely expressed in immune cells including monocytes,macrophages,dendritic cells(DC),neutrophils,T cells and B cells during their development,differentiation and activation.However,the functional importance of immune-related lncRNAs is just emerging to be characterized.In this review,we discuss the up-to-date knowledge of lncRNAs in immune regulation.
基金funded by US National Institutes of Health(NIH)-NIAID R21AI151943.
文摘Macrophages are dominant innate immune cells.They demonstrate remarkable het-erogeneity and plasticity that are essential for homeostasis and host defense.The heterogeneity of tissue macrophages is shaped by the ontogeny,tissue factors,and environmental signals,a pattern in a tissue-associated latitudinal manner.At the same time,macrophages have long been considered as mainly plastic cells.These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation,including coordination of signal trans-ducer,epigenetic elements,and transcription factors,conclusively determine the macrophage phenotypes and functions.With the development of cutting-edge technologies,such as fate-mapping,single-cell transcriptomics,ipsc platform,nanotherapeutic materials,etc.,our under-standing of macrophage biology and the roles in the pathogenesis of diseases is much advanced.This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases.The latitudinal regulation covers the tissue macrophage or-igins,tissue factors,and environmental signals,reflecting the macrophage heterogeneity.The lon-gitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases(i.e.,inflammatory bowel disease).In addition,how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.
