According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the rise.Neuropsychiatric condition...According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the rise.Neuropsychiatric conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune diseases.Recent studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory response.When the BBB is intact,autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and CD.However,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are uncertain.In this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.展开更多
Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals ...Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atohl to regulate hair cell regeneration in the mammalian cochlea.展开更多
The response of immune cells in cardiac injury is divided into three continuous phases:inflammation,proliferation and maturation.The kinetics of the inflammatory and proliferation phases directly influence the tissue ...The response of immune cells in cardiac injury is divided into three continuous phases:inflammation,proliferation and maturation.The kinetics of the inflammatory and proliferation phases directly influence the tissue repair.In cardiac homeostasis,cardiac tissue resident macrophages(cTMs)phagocytose bacteria and apoptotic cells.Meanwhile,NK cells prevent the maturation and transport of inflammatory cells.After cardiac injury,cTMs phagocytose the dead cardiomyocytes(CMs),regulate the proliferation and angiogenesis of cardiac progenitor cells.NK cells prevent the cardiac fibrosis,and promote vascularization and angiogenesis.Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage.Reversely,type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage.Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines,and then release anti-inflammatory cytokines and growth factors,which regulate cardiac remodeling.In this process,dendritic cells(DCs)mediate the regulation of monocyte and macrophage recruitment.Recruited eosinophils and Mast cells(MCs)release some mediators which contribute to coronary vasoconstriction,leukocyte recruitment,formation of new blood vessels,scar formation.In adaptive immunity,effector T cells,especially Th17 cells,lead to the pathogenesis of cardiac fibrosis,including the distal fibrosis and scar formation.CMs protectors,Treg cells,inhibit reduce the inflammatory response,then directly trigger the regeneration of local progenitor cell via IL-10.B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.展开更多
Interferon regulatory factors(IRFs)play pivotal and critical roles in innate and adaptive immune responses;thus,precise and stringent regulation of the stability and activation of IRFs in physiological processes is ne...Interferon regulatory factors(IRFs)play pivotal and critical roles in innate and adaptive immune responses;thus,precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary.The stability and activities of IRFs are directly or indirectly targeted by endogenous and exogenous proteins in an ubiquitin-dependent manner.However,few reviews have summarized how host E3 ligases/DUBs or viral proteins regulate IRF stability and activity.Additionally,with recent technological developments,details about the ubiquitination of IRFs have been continuously revealed.As knowledge of how these proteins function and interact with IRFs may facilitate a better understanding of the regulation of IRFs in immune responses or other biological processes,we summarized current studies on the direct ubiquitination of IRFs,with an emphasis on how these proteins interact with IRFs and affect their activities,which may provide exciting targets for drug development by regulating the functions of specific E3 ligases.展开更多
Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of ...Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site,orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation.All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.展开更多
Autophagy,a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway,is an important mechanism for cellular self-protection in eukaryotes.Autophagy plays essential roles in cell s...Autophagy,a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway,is an important mechanism for cellular self-protection in eukaryotes.Autophagy plays essential roles in cell survival,renewal,material reuse and the maintenance of homeostasis.This paper reviews recent advances in understanding the physiological function of autophagy and its possible roles in auditory diseases.We focused our review on original publications on animal models,drug models,and molecular mechanisms of hearing impairment involved in the dysregulation of autophagy.As research on the mechanisms of autophagy has deepened,it has become obvious that autophagy plays essential roles not only in cell survival,but the occurrence and development of a variety of auditory-related disorder,including aminoglycoside-induced hearing loss,age-related hearing loss,and noise-induced hearing loss.While clinical treatment of such conditions via regulation of the development of autophagy is a novel idea,more time is needed to fully elucidate the specific regulatory pathways and modes of autophagy in auditory diseases.The continued study of the mechanisms and regulation of autophagy in auditory diseases will be of great significance for the future treatment and prevention of these conditions.展开更多
Mitochondria are highly mobile organelles due to fission,fusion,transport,and mitophagy,and these processes are known as mitochondrial dynamics.Mitochondrial dynamics play an important role in energy production,cell d...Mitochondria are highly mobile organelles due to fission,fusion,transport,and mitophagy,and these processes are known as mitochondrial dynamics.Mitochondrial dynamics play an important role in energy production,cell division,cell differentiation,and cell death.In the past decade,numerous studies have revealed the importance of mitochondrial metabolism in immunity,and mitochondrial dynamics are essential for immune responses mediated by various cell types.In this review,we mainly discuss the role of mitochondrial dynamics in activation,differentiation,cytokine production,and the activity of related pathways in immune cells,particularly T cells,B cells,and other cells involved in the innate immune response.展开更多
基金supported by distinguished Young Scientist Fund of NSFC(82125016)National Natural Science Foundation of China,Key Program(82230061)+3 种基金Zhejiang Provincial Natural Science Foundation of China(LR19C080001,LQ21H030013)supported by the National Key Research and Development Program of China(2018YFD0500100)the National Natural Science Foundation of China(81572651/81771675)the 111 Program(D20036).
文摘According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the rise.Neuropsychiatric conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune diseases.Recent studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory response.When the BBB is intact,autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and CD.However,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are uncertain.In this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.
基金This work was supported by grants from the National Basic Research Program of China （973 Program, No. 2015CB965000）, the National Natural Science Foundation of China （Nos. 81570911, 81470692, 81470687, 81371094, 81230019, 81500790, 81570921, 31500852, and 31501194）, the Jiangsu Province Natural Science Foundation （Nos. BIC20150022, BK20140620, and BK20150598）, and the Fundamental Research Funds for the Central Universities （Nos. 2242014R30022, and 021414380037）.
文摘Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atohl to regulate hair cell regeneration in the mammalian cochlea.
基金supported by the National Key R&D Program of China(2018YFA0800503)excellent young scientist foundation of N SFC(31822017)+2 种基金supported by Zhejiang Provincial Natural Science Foundation of China under Grant NO.LR19C080001supported by the National Natural Science Foundation of China(81572651/81771675)supported by the Fundamental Research Funds for the Central Universities.
文摘The response of immune cells in cardiac injury is divided into three continuous phases:inflammation,proliferation and maturation.The kinetics of the inflammatory and proliferation phases directly influence the tissue repair.In cardiac homeostasis,cardiac tissue resident macrophages(cTMs)phagocytose bacteria and apoptotic cells.Meanwhile,NK cells prevent the maturation and transport of inflammatory cells.After cardiac injury,cTMs phagocytose the dead cardiomyocytes(CMs),regulate the proliferation and angiogenesis of cardiac progenitor cells.NK cells prevent the cardiac fibrosis,and promote vascularization and angiogenesis.Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage.Reversely,type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage.Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines,and then release anti-inflammatory cytokines and growth factors,which regulate cardiac remodeling.In this process,dendritic cells(DCs)mediate the regulation of monocyte and macrophage recruitment.Recruited eosinophils and Mast cells(MCs)release some mediators which contribute to coronary vasoconstriction,leukocyte recruitment,formation of new blood vessels,scar formation.In adaptive immunity,effector T cells,especially Th17 cells,lead to the pathogenesis of cardiac fibrosis,including the distal fibrosis and scar formation.CMs protectors,Treg cells,inhibit reduce the inflammatory response,then directly trigger the regeneration of local progenitor cell via IL-10.B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.
基金supported by the National Key Research and Development Program of China(2018YFA0800503 and 2018YFD0500100)an excellent young scientist foundation of NSFC(31822017)+2 种基金Zhejiang Provincial Natural Science Foundation of China(LR19C080001)the National Natural Science Foundation of China(81572651 and 81771675)the Fundamental Research Funds for the Central Universities。
文摘Interferon regulatory factors(IRFs)play pivotal and critical roles in innate and adaptive immune responses;thus,precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary.The stability and activities of IRFs are directly or indirectly targeted by endogenous and exogenous proteins in an ubiquitin-dependent manner.However,few reviews have summarized how host E3 ligases/DUBs or viral proteins regulate IRF stability and activity.Additionally,with recent technological developments,details about the ubiquitination of IRFs have been continuously revealed.As knowledge of how these proteins function and interact with IRFs may facilitate a better understanding of the regulation of IRFs in immune responses or other biological processes,we summarized current studies on the direct ubiquitination of IRFs,with an emphasis on how these proteins interact with IRFs and affect their activities,which may provide exciting targets for drug development by regulating the functions of specific E3 ligases.
基金supported by the National Key R&D Program of China (No. 2020YFA0113600 and 2017YFA0105201)National Natural Sciences Foundation of China (81822017 and 32070955)。
文摘Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site,orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation.All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.
文摘Autophagy,a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway,is an important mechanism for cellular self-protection in eukaryotes.Autophagy plays essential roles in cell survival,renewal,material reuse and the maintenance of homeostasis.This paper reviews recent advances in understanding the physiological function of autophagy and its possible roles in auditory diseases.We focused our review on original publications on animal models,drug models,and molecular mechanisms of hearing impairment involved in the dysregulation of autophagy.As research on the mechanisms of autophagy has deepened,it has become obvious that autophagy plays essential roles not only in cell survival,but the occurrence and development of a variety of auditory-related disorder,including aminoglycoside-induced hearing loss,age-related hearing loss,and noise-induced hearing loss.While clinical treatment of such conditions via regulation of the development of autophagy is a novel idea,more time is needed to fully elucidate the specific regulatory pathways and modes of autophagy in auditory diseases.The continued study of the mechanisms and regulation of autophagy in auditory diseases will be of great significance for the future treatment and prevention of these conditions.
基金This review was supported by the Excellent Young Scientist Foundation of NSFC(grant No.31822017)the Zhejiang Provincial Natural Science Foundation of China under grant no.LR19C080001+1 种基金the National Natural Science Foundation of China(grant nos.81572651 and 81771675)the Fundamental Research Funds for the Central Universities。
文摘Mitochondria are highly mobile organelles due to fission,fusion,transport,and mitophagy,and these processes are known as mitochondrial dynamics.Mitochondrial dynamics play an important role in energy production,cell division,cell differentiation,and cell death.In the past decade,numerous studies have revealed the importance of mitochondrial metabolism in immunity,and mitochondrial dynamics are essential for immune responses mediated by various cell types.In this review,we mainly discuss the role of mitochondrial dynamics in activation,differentiation,cytokine production,and the activity of related pathways in immune cells,particularly T cells,B cells,and other cells involved in the innate immune response.
