Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Autotoxicity stress is the principal factor in peach replant problem.Benzoic acid(BA)is known as a critical autotoxin in replant problem,and causes an obvious inhibitory effect on peach growth.Small heat shock protein...Autotoxicity stress is the principal factor in peach replant problem.Benzoic acid(BA)is known as a critical autotoxin in replant problem,and causes an obvious inhibitory effect on peach growth.Small heat shock proteins(sHSPs)have been reported to play pivotal roles in a variety of physiological and biological processes in various plants.Nevertheless,little is known about the functions and the underlying physiological mechanisms of sHSPs under autotoxicity stress.Here,we identified PpHSP20-26 of peach(Prunus persica)and deciphered its role in BA stress response.PpHSP20-26 was significantly induced by BA treatment.Overexpression of PpHSP20-26 elevated BA tolerance in Arabidopsis and peach plants,whereas down-regulation of PpHSP20-26 in peach through virus-induced gene silencing enhanced BA sensitivity.Compared to the control,the PpHSP20-26-overexpressing plants exhibited lower contents of reactive oxygen species(ROS)and higher activities of antioxidant enzymes.Furthermore,PpHSP20-26 regulated the transcripts of stress-responsive genes including CAT,SOD,APX,GPX,DHAR,and ABC transporters in overexpressing Arabidopsis and silenced peach plants.Taken together,these data suggest that PpHSP20-26 plays a positive role in peach response to BA stress by,at least partly,regulating ROS metabolism and stress-responsive gene expression.Our findings will be of great importance for further understanding the roles of sHSPs genes in autotoxicity stress,and assist crop breeding in mitigating replant problem.展开更多
Background:Metabolic abnormalities are considered to play a key regulatory role in vascular remodeling of pulmonary arterial hypertension.However,to date,there is a paucity of research documenting the changes in metab...Background:Metabolic abnormalities are considered to play a key regulatory role in vascular remodeling of pulmonary arterial hypertension.However,to date,there is a paucity of research documenting the changes in metabolome profiles within the su-pernatants of pulmonary artery smooth muscle cells(PASMC)during their transition from a contractile to a synthetic phenotype.Methods:CCK-8 and Edu staining assays were used to evaluate the cell viability and proliferation of human PASMCs.IncuCyte ZOOM imaging system was used to continuously and automatically detect the migration of the PASMCs.A targeted me-tabolomics profiling was performed to quantitatively analyze 121 metabolites in the supernatant.Orthogonal partial least squares discriminant analysis was used to dis-criminate between PDGF-BB-induced PASMCs and controls.Metabolite set enrich-ment analysis was adapted to exploit the most disturbed metabolic pathways.Results:Human PASMCs exhibited a transformation from contractile phenotype to synthetic phenotype after PDGF-BB induction,along with a significant increase in cell viability,proliferation,and migration.Metabolites in the supernatants of PASMCs treated with or without PDGF-BB were well profiled.Eleven metabolites were found to be significantly upregulated,whereas seven metabolites were downregulated in the supernatants of PASMCs induced by PDGF-BB compared to the vehicle-treated cells.Fourteen pathways were involved,and pyruvate metabolism pathway was ranked first with the highest enrichment impact followed by glycolysis/gluconeogen-esis and pyrimidine metabolism.Conclusions:Significant and extensive metabolic abnormalities occurred during the phenotypic transformation of PASMCs.Disturbance of pyruvate metabolism pathway might contribute to pulmonary vascular remodeling.展开更多
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by the National Natural Science Foundation of China(Grant No.32272645)China Agriculture Research System of MOF and MARA(Grant No.CARS-30)Changsha Municipal Natural Science Foundation(Grant No.kq2208135).
文摘Autotoxicity stress is the principal factor in peach replant problem.Benzoic acid(BA)is known as a critical autotoxin in replant problem,and causes an obvious inhibitory effect on peach growth.Small heat shock proteins(sHSPs)have been reported to play pivotal roles in a variety of physiological and biological processes in various plants.Nevertheless,little is known about the functions and the underlying physiological mechanisms of sHSPs under autotoxicity stress.Here,we identified PpHSP20-26 of peach(Prunus persica)and deciphered its role in BA stress response.PpHSP20-26 was significantly induced by BA treatment.Overexpression of PpHSP20-26 elevated BA tolerance in Arabidopsis and peach plants,whereas down-regulation of PpHSP20-26 in peach through virus-induced gene silencing enhanced BA sensitivity.Compared to the control,the PpHSP20-26-overexpressing plants exhibited lower contents of reactive oxygen species(ROS)and higher activities of antioxidant enzymes.Furthermore,PpHSP20-26 regulated the transcripts of stress-responsive genes including CAT,SOD,APX,GPX,DHAR,and ABC transporters in overexpressing Arabidopsis and silenced peach plants.Taken together,these data suggest that PpHSP20-26 plays a positive role in peach response to BA stress by,at least partly,regulating ROS metabolism and stress-responsive gene expression.Our findings will be of great importance for further understanding the roles of sHSPs genes in autotoxicity stress,and assist crop breeding in mitigating replant problem.
基金Joint Fund of Science and Technology R&D Plan of Henan Province,Grant/Award Number:232103810056Special Project for Key R&D and Promotion of Henan Province,Grant/Award Number:232102311233 and 242102311034National Natural Science Foundation of China,Grant/Award Number:82170058 and 82241007。
文摘Background:Metabolic abnormalities are considered to play a key regulatory role in vascular remodeling of pulmonary arterial hypertension.However,to date,there is a paucity of research documenting the changes in metabolome profiles within the su-pernatants of pulmonary artery smooth muscle cells(PASMC)during their transition from a contractile to a synthetic phenotype.Methods:CCK-8 and Edu staining assays were used to evaluate the cell viability and proliferation of human PASMCs.IncuCyte ZOOM imaging system was used to continuously and automatically detect the migration of the PASMCs.A targeted me-tabolomics profiling was performed to quantitatively analyze 121 metabolites in the supernatant.Orthogonal partial least squares discriminant analysis was used to dis-criminate between PDGF-BB-induced PASMCs and controls.Metabolite set enrich-ment analysis was adapted to exploit the most disturbed metabolic pathways.Results:Human PASMCs exhibited a transformation from contractile phenotype to synthetic phenotype after PDGF-BB induction,along with a significant increase in cell viability,proliferation,and migration.Metabolites in the supernatants of PASMCs treated with or without PDGF-BB were well profiled.Eleven metabolites were found to be significantly upregulated,whereas seven metabolites were downregulated in the supernatants of PASMCs induced by PDGF-BB compared to the vehicle-treated cells.Fourteen pathways were involved,and pyruvate metabolism pathway was ranked first with the highest enrichment impact followed by glycolysis/gluconeogen-esis and pyrimidine metabolism.Conclusions:Significant and extensive metabolic abnormalities occurred during the phenotypic transformation of PASMCs.Disturbance of pyruvate metabolism pathway might contribute to pulmonary vascular remodeling.
