During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiolo...During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further investigated.Since China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the CSS.In this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling.Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine metabolism.The microgravity condition blocked the thiamine intake in hPSC-CMs.The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle.It decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs.More importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity.This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research.These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.展开更多
Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation...Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.展开更多
Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to preve...Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to prevent or alleviate cardiac fibrosis.Curcumin,a natural molecule with antifibrotic activity,is encapsulated in the exosomes that are isolated from bone marrow-derived mesenchymal stem cells to enhance its water solubility and bioavailability.These composite exosomes are efficiently internalised by fibroblasts and effectively inhibit their transition to myofibroblasts in vitro.Decellularized porcine cardiac extracellular matrix(dECM)hydrogel is used as the carrier for delivering these composite exosomes to the infarcted myocardium,not only improving the retention of exosomes but also providing mechani-cal support and structural protection.Injection of this hydrogel into the infarcted heart of a mouse MI model leads to a decrease in collagen deposition,alleviation of fibrosis,a reduction in infarct size,and an improvement in cardiac function.The reported composite hydrogel comprising natural materials and biomolecules exhibits good biocompatibility and bioactivity.Altogether,this study demonstrates that the dECM hydrogel is a suitable platform for the local delivery of antifibrotic biomolecule-encapsulating exo-somes to prevent myocardial fibrosis after MI and have great potential for the treatment of MI in clinical settings.展开更多
Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery...Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery,necrosis of myocardial cells,inflammation,and myocardial fibrosis.Aiming at the treatment of different stages of MI,in this work,an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor(VEGF)and silk fibroin(SF)microspheres containing bone morphogenetic protein 9(BMP9)for releasing VEGF and BMP9 to realize their respective functions.The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days,facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage,respectively.Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size.Taken together,these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function,showing a promising potential for cardiac clinical application.展开更多
Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of thr...Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.展开更多
Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing ...Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing inflammatory cytokines including IL-1β and IL-18.1 However,the molecular mechanisms underlying activation of the NLRP3 inflammasome remain largely unknown.展开更多
Myocardial infarction(MI)is one of the common cardiovascular diseases that occurs with a blockage in one or more of the coronary arteries to lead to the damage of the myocardium,resulting in a lifethreatening conditio...Myocardial infarction(MI)is one of the common cardiovascular diseases that occurs with a blockage in one or more of the coronary arteries to lead to the damage of the myocardium,resulting in a lifethreatening condition.To repair the damaged myocardium in MI,researchers are looking forwards to new ways to postpone the progression of myocardial injury.Cardiac patches,the scaffolds layered on the heart surface,can provide mechanical support for the infarction site and improve cardiac function by delivering various bioactive factors or cells,showing considerable curative effect in the treatment of MI.Biomaterials with certain biocompatibility and mechanical properties have received widespread attention for the application in cardiac patches.In this review,we focus on the recent progress on these biomaterialsbased cardiac patches,which could be categorized into two types according to the sources of materials including(ⅰ)natural materials and(ⅱ)synthetic materials.The major advantages and current challenges of each type are discussed and a brief perspective on the future research directions is presented.展开更多
基金This study was supported by the National Key R&D Program of China(2022YFA1104300)the Space Medical Experiment Project of China Manned Space Program(HYZHXM01018)+4 种基金the National Natural Science Foundation of China(82241202)Scientific Innovation Project of the State Key Laboratory of Radiation Medicine and Protection(GZC00101)The Natural Science Foundation of the Jiangsu Higher Education Institutions of China(21KJB310003)Jiangsu Cardiovascular Medicine Innovation Center(CXZX202210)National Center for International Research(2017B01012).
文摘During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further investigated.Since China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the CSS.In this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling.Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine metabolism.The microgravity condition blocked the thiamine intake in hPSC-CMs.The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle.It decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs.More importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity.This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research.These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.
基金financially supported by the National Natural Science Foundation of China (Nos.92168203 and 22175125)the Extracurricular Scientific Research Project for Students of Suzhou Medical College of Soochow University (No.2021YXBKWKY070)+3 种基金the Scientific Research Innovation Project for Graduate Students of Jiangsu Province (No.KYCX22_3189)the Introduction Project of Clinical Medicine Expert Team for Suzhou (No.SZYJTD201704)the Natural Science Foundation of the Jiangsu Higher Education Insti-tutions of China (No.21KJA150008)the Priority Academic Pro-gram Development of Jiangsu Higher Education Institutions (PAPD).
文摘Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.
基金supported by the National Natural Science Foun-dation of China(no.92168203)Jiangsu Cardiovascular Medicine Innovation Center(no.CXZX202210)+1 种基金the Scientific Research In-novation Project for Graduate Students of Jiangsu Province(no.KYCX22_3189)the Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function,Soochow University,and the Priority Academic Program Development of Jiangsu Higher Ed-ucation Institutions(PAPD).
文摘Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to prevent or alleviate cardiac fibrosis.Curcumin,a natural molecule with antifibrotic activity,is encapsulated in the exosomes that are isolated from bone marrow-derived mesenchymal stem cells to enhance its water solubility and bioavailability.These composite exosomes are efficiently internalised by fibroblasts and effectively inhibit their transition to myofibroblasts in vitro.Decellularized porcine cardiac extracellular matrix(dECM)hydrogel is used as the carrier for delivering these composite exosomes to the infarcted myocardium,not only improving the retention of exosomes but also providing mechani-cal support and structural protection.Injection of this hydrogel into the infarcted heart of a mouse MI model leads to a decrease in collagen deposition,alleviation of fibrosis,a reduction in infarct size,and an improvement in cardiac function.The reported composite hydrogel comprising natural materials and biomolecules exhibits good biocompatibility and bioactivity.Altogether,this study demonstrates that the dECM hydrogel is a suitable platform for the local delivery of antifibrotic biomolecule-encapsulating exo-somes to prevent myocardial fibrosis after MI and have great potential for the treatment of MI in clinical settings.
基金This work was supported by the National Natural Science Foundation of China(91839101,21774086,81770258,81900317)the Suzhou Municipal Science and Technology Foundation(SYS2018026)the Introduction Project of Clinical Medicine Expert Team for Suzhou(SZYJTD201704).
文摘Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery,necrosis of myocardial cells,inflammation,and myocardial fibrosis.Aiming at the treatment of different stages of MI,in this work,an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor(VEGF)and silk fibroin(SF)microspheres containing bone morphogenetic protein 9(BMP9)for releasing VEGF and BMP9 to realize their respective functions.The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days,facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage,respectively.Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size.Taken together,these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function,showing a promising potential for cardiac clinical application.
基金This work was supported by the National Natural Science Foundation of China(81870194 and 91849122 to Y.L.,81873528 and 81670358 to Y.-H.S.,91839101 to Z.S.,and U1601227 to X.-Y.Y.)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.L.)Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704).
文摘Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.
基金This work was supported by the National Natural Science Foundation of China(NSFC,No.91849122 to Y.L,No.81870194 to Y.L)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.L.)+1 种基金National Natural Science Foundation of China(No.91839101 to Z.S.,No.U1601227 to X.Y.)Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704).
文摘Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing inflammatory cytokines including IL-1β and IL-18.1 However,the molecular mechanisms underlying activation of the NLRP3 inflammasome remain largely unknown.
基金supported by the National Natural Science Foundation of China(Nos.91839101,21774086)the Natural Science Foundation of Jiangsu Province(No.BK20180093)+4 种基金the Suzhou Municipal Science and Technology Foundation(No.SYS2018026)the Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704)the Project of Improvement in Clinical Trial Ability of Cardiovascular Group of the First Affiliated Hospital of Soochow University(No.201900180019)the Application Research on New Platelet Function-detecting Technology in Thrombosis Prevention(No.31010303010982)the Priority Academic Program Development of Jiangsu Higher Education。
文摘Myocardial infarction(MI)is one of the common cardiovascular diseases that occurs with a blockage in one or more of the coronary arteries to lead to the damage of the myocardium,resulting in a lifethreatening condition.To repair the damaged myocardium in MI,researchers are looking forwards to new ways to postpone the progression of myocardial injury.Cardiac patches,the scaffolds layered on the heart surface,can provide mechanical support for the infarction site and improve cardiac function by delivering various bioactive factors or cells,showing considerable curative effect in the treatment of MI.Biomaterials with certain biocompatibility and mechanical properties have received widespread attention for the application in cardiac patches.In this review,we focus on the recent progress on these biomaterialsbased cardiac patches,which could be categorized into two types according to the sources of materials including(ⅰ)natural materials and(ⅱ)synthetic materials.The major advantages and current challenges of each type are discussed and a brief perspective on the future research directions is presented.
