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
Hard carbon(HC)has emerged as one of the superior anode materials for sodium-ion batteries(SIBs),with its electrochemical performance significantly influenced by the presence of oxygen functional groups and its closed...Hard carbon(HC)has emerged as one of the superior anode materials for sodium-ion batteries(SIBs),with its electrochemical performance significantly influenced by the presence of oxygen functional groups and its closed pore structure.However,current research on the structural adjustment of these oxygen functional groups and the closed pore architecture within HC remains limited.Herein,energy-efficient and contamination-free spark plasma sintering technology was employed to tune the structure of coconut-shell HC,resulting in significant adjustments to the content of carboxyl(decreasing from 5.71 at%to 2.12 at%)and hydroxyl groups(decreasing from 7.73 at%to 6.26 at%).Crucially,these modifications reduced the irreversible reaction of oxygen functional groups with Na^(+).Simultaneously,a substantial number of closed pores with an average diameter of 1.22 nm were generated within the HC,offering an ideal environment for efficient Na^(+)accommodation.These structural changes resulted in a remarkable improvement in the electrochemical performance of the modified HC.The reversible specific capacity of the modified HC surged from 73.89 mAh·g^(-1)to an impressive 251.97 m Ah·g^(-1)at a current density of 50 mA·g^(-1).Even at 400 mA·g^(-1),the reversible specific capacity increased significantly from 14.55 to 85.44 mAh·g^(-1).Hence,this study provides a novel perspective for designing tailored HC materials with the potential to develop high-performance SIBs.展开更多
Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial...Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.展开更多
Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypert...Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.展开更多
Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia rem...Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.展开更多
1 CURRENT KNOWLEDGE OF STEM CELLS IN PULMONARY HYPERTENSION(PH)1.1 PH Pulmonary hypertension(PH)is a clinical and pathophysiological syndrome characterized by structural or functional changes in the pulmonary arteries...1 CURRENT KNOWLEDGE OF STEM CELLS IN PULMONARY HYPERTENSION(PH)1.1 PH Pulmonary hypertension(PH)is a clinical and pathophysiological syndrome characterized by structural or functional changes in the pulmonary arteries caused by various heterogeneous diseases and different pathogenic mechanisms.This results in elevated pulmonary vascular resistance and increased pulmonary arterial pressure,eventually leading to right heart failure and potentially death.^(1)PH is categorized into5 groups:pulmonary arterial hypertension(PAH,group 1),PH associated with left heart disease(group 2),PH associated with lung diseases and/or hypoxia(group 3),PH associated with pulmonary artery obstructions(group 4),PH with unclear and/or multifactorial mechanisms(group 5).展开更多
Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic...Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.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.
基金financially supported by the National Natural Science Foundation of China(No.52062012)Guangdong Province Key Discipline Construction Project(No.2021ZDJS102)+2 种基金the Innovation Team of Universities of Guangdong Province(No.2022KCXTD030)the Special Fund for Science and Technology Innovation Cultivation of Guangdong University Students(No.pdjh2023b0549)the Student Academic Fund of Foshan University(No.xsjj202206kjb02)。
文摘Hard carbon(HC)has emerged as one of the superior anode materials for sodium-ion batteries(SIBs),with its electrochemical performance significantly influenced by the presence of oxygen functional groups and its closed pore structure.However,current research on the structural adjustment of these oxygen functional groups and the closed pore architecture within HC remains limited.Herein,energy-efficient and contamination-free spark plasma sintering technology was employed to tune the structure of coconut-shell HC,resulting in significant adjustments to the content of carboxyl(decreasing from 5.71 at%to 2.12 at%)and hydroxyl groups(decreasing from 7.73 at%to 6.26 at%).Crucially,these modifications reduced the irreversible reaction of oxygen functional groups with Na^(+).Simultaneously,a substantial number of closed pores with an average diameter of 1.22 nm were generated within the HC,offering an ideal environment for efficient Na^(+)accommodation.These structural changes resulted in a remarkable improvement in the electrochemical performance of the modified HC.The reversible specific capacity of the modified HC surged from 73.89 mAh·g^(-1)to an impressive 251.97 m Ah·g^(-1)at a current density of 50 mA·g^(-1).Even at 400 mA·g^(-1),the reversible specific capacity increased significantly from 14.55 to 85.44 mAh·g^(-1).Hence,this study provides a novel perspective for designing tailored HC materials with the potential to develop high-performance SIBs.
基金Program of Natural Science Foundation of Shanghai,Grant/Award Number:21ZR1453800 and 22ZR1452400Program of National Natural Science Foundation of China,Grant/Award Number:82370057+3 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Shanghai Municipal Health Commission,Grant/Award Number:20204Y0384Program of National Key Research and Development Project of China,Grant/Award Number:2023YFC2509500。
文摘Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.
基金Program of the National Natural Science Foundation of China,Grant/Award Number:81700045,81870042 and 82200065The Department Development Fund of Shanghai Pulmonary Hospital,Grant/Award Number:201906-0314+2 种基金The Program of Shanghai Pulmonary Hospital,Grant/Award Number:FKLY20011The Three-year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals,Grant/Award Number:SHDC2020CR4021Young Talent Program of Shanghai Municipal Health Commission,Grant/Award Number:2022YQ070。
文摘Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.
基金Central University Basic Research Fund of China,Grant/Award Number:22120220562National Natural Science Foundation of China,Grant/Award Number:81870044+1 种基金Natural Science Foundation of Shanghai,Grant/Award Number:201409004100 and 21ZR1453800Shanghai Pulmonary Hospital,Grant/Award Number:FKLY20005 and fkzr2320。
文摘Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.
基金Program of Hainan Province's Key Research and Development ProjectGrant/Award Number:ZDYF2024SHFZ057+1 种基金Program of National Natural Science Foundation of ChinaGrant/Award Number:82370057。
文摘1 CURRENT KNOWLEDGE OF STEM CELLS IN PULMONARY HYPERTENSION(PH)1.1 PH Pulmonary hypertension(PH)is a clinical and pathophysiological syndrome characterized by structural or functional changes in the pulmonary arteries caused by various heterogeneous diseases and different pathogenic mechanisms.This results in elevated pulmonary vascular resistance and increased pulmonary arterial pressure,eventually leading to right heart failure and potentially death.^(1)PH is categorized into5 groups:pulmonary arterial hypertension(PAH,group 1),PH associated with left heart disease(group 2),PH associated with lung diseases and/or hypoxia(group 3),PH associated with pulmonary artery obstructions(group 4),PH with unclear and/or multifactorial mechanisms(group 5).
基金financially supported by the Shaanxi Province Key Project for Social Development(No.2022SF-205).
文摘Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.
