Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr...Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.展开更多
We sincerely thank the authors of the commentary1 for their thoughtful analysis and constructive critique of our systematic review on ischemic preconditioning(IPC)and placebo effects in exercise capacity and athletic ...We sincerely thank the authors of the commentary1 for their thoughtful analysis and constructive critique of our systematic review on ischemic preconditioning(IPC)and placebo effects in exercise capacity and athletic performance.2Their attention to methodological details,particularly concerning the inclusion and timing of warm-up protocols across studies,is commendable and contributes meaningfully to the ongoing refinement of IPC research in sports science.展开更多
We highly commend Dr Souza et al.1for their systematic review research.The authors conducted a detailed investigation into the effects of ischemic preconditioning(IPC)on athletic performance,comparing it with placebo ...We highly commend Dr Souza et al.1for their systematic review research.The authors conducted a detailed investigation into the effects of ischemic preconditioning(IPC)on athletic performance,comparing it with placebo and no-intervention conditions.The study found that while IPC demonstrated superior effects over the no-intervention group in certain metrics(e.g.,time to exhaustion),its performance did not significantly surpass that of the placebo group.This suggests that the potential benefits of IPC may partially stem from participants’psychological expectations,or placebo effects.The study also highlighted the significant impact of placebo interventions on athletic performance,emphasizing the importance of distinguishing between placebo and no-intervention conditions in experimental designs.展开更多
Objective Stroke is a main cause of disability and mortality worldwide.It has been reported that ischemic preconditioning(IP)has neuroprotective effects against stroke.This study aimed to verify the mechanism by which...Objective Stroke is a main cause of disability and mortality worldwide.It has been reported that ischemic preconditioning(IP)has neuroprotective effects against stroke.This study aimed to verify the mechanism by which calcium-sensing recep-tor(Casr)inhibition-mediated M2 microglial transformation in the IP protects against stroke,which will provide a potential therapeutic target for stroke.Methods Middle cerebral artery occlusion(MCAO)rats and oxygen-glucose deprivation(OGD)neurons were used in this study.IP was induced via the transient MCAO and OGD methods.RNA sequencing(RNA-Seq)was used to explore the underlying key molecules.Western blotting and immunohistochemistry were performed to detect the expression of Casr and the M1 and M2 microglial markers.CCK8 was used to detect cell viability.The calcium concentration was detected via the use of Fluo-4 AM,a fluorescence probe.The Casr inhibitor NPS2143 and the Casr activator R568 were used to explore the role of Casr in M2 microglial transformation and neuroprotection.Results We first revealed that IP induced M2 microglial transformation in ischemic injury.In addition,MCAO injury increased Casr expression and the calcium concentration,which was inhibited by IP.Furthermore,Casr activation inhibited the M2 microglial transformation induced by IP.Finally,we found that Casr inhibition improved the survival rate,alleviated neurological deficits,and reduced the infarct volume induced by MCAO.Conclusions We confirmed that Casr-related neuroprotection induced by IP is associated with the transformation of M2 microglia.These findings can be used to understand the protective mechanisms of IP against ischemic stroke.展开更多
Mesenchymal stem cells(MSCs)possess unique properties such as immunomodu-lation,paracrine actions,multilineage differentiation,and self-renewal.Therefore,MSC-based cell therapy is an innovative approach to treating va...Mesenchymal stem cells(MSCs)possess unique properties such as immunomodu-lation,paracrine actions,multilineage differentiation,and self-renewal.Therefore,MSC-based cell therapy is an innovative approach to treating various degenera-tive illnesses,including cardiovascular diseases.However,several challenges,including low transplant survival rates,low migration to the ischemic myocar-dium,and poor tissue retention,restrict the application of MSCs in clinical settings.These undesirable cell therapy outcomes mainly originated due to the overproduction of reactive oxygen species(ROS)in the injured heart.MSCs'stress-coping capacity can be enhanced by preconditioning them under conditions similar to the microenvironment of wounded tissues.Hydrogen peroxide(H_(2)O_(2))is a ROS that has been shown to activate protective cellular mechanisms such as survival,proliferation,migration,paracrine effects,and differentiation at suble-thal doses.These processes are induced via phosphatidylinositol 3-kinase/protein kinase B,p38 mitogen-activated protein kinases,c-Jun N-terminal kinase,Janus kinase/signal transducer and activator of the transcription,Notch1,and Wnt sig-naling pathways.H_(2)O_(2) preconditioning could lead to many clinical benefits,including ischemic injury reduction,enhanced survival of cellular transplants,and tissue regeneration.In this review,we present an overview of stem cell preconditioning methods and the biological functions activated by H_(2)O_(2) precondi-tioning.Furthermore,this review explores the molecular mechanisms underlying the protective cellular functions stimulated under H_(2)O_(2) preconditioning.展开更多
Based on waveform fitting,full waveform inversion(FWI)is an important inversion method with the ability to reconstruct multi-parameter models in high precision.However,the strong nonlinear equation used in FWI present...Based on waveform fitting,full waveform inversion(FWI)is an important inversion method with the ability to reconstruct multi-parameter models in high precision.However,the strong nonlinear equation used in FWI presents the following challenges,such as low convergence efficiency,high dependence on the initial model,and the energy imbalance in deep region of the inverted model.To solve these inherent problems,we develop a timedomain elastic FWI method based on gradient preconditioning with the following details:(1)the limited memory Broyden Fletcher Goldfarb Shanno method with faster convergence is adopted to im-prove the inversion stability;(2)a multi-scaled inversion strategy is used to alleviate the nonlinear inversion instead of falling into the local minimum;(3)in addition,the pseudo-Hessian preconditioned illumination operator is involved for preconditioning the parameter gradients to improve the illumination equilibrium degree of deep structures.Based on the programming implementation of the new method,a deep depression model with five diffractors is used for testing.Compared with the conventional elastic FWI method,the technique proposed by this study has better effectiveness and accuracy on the inversion effect and con-vergence,respectively.展开更多
In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydro...In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary hypertension.Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured tissue.They also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell survival.Ferroptosis,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to cancer.The lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular structures.Understanding these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related diseases.This editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis pathway.Ferroptosis presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention.Further research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.展开更多
Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)...Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.展开更多
Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies,and pretreatment has proven to enhance cell vitality and function.In a recent publication,Li et al explored a new combination o...Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies,and pretreatment has proven to enhance cell vitality and function.In a recent publication,Li et al explored a new combination of pretreatment condi-tions.Here,we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.展开更多
Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods...Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10- min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Results Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region （P 〈 0.01 vs 10-min ischemia group）. Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates（P〈0.01 vs 10-min ischemia group）.Conelusion Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.展开更多
Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually ...Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually lead to different results.The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation（OGD）injury in vitro.Methods Rat hippocampal slices under normoxic conditions（95%O2/5%CO2）were pre-exposed to sevoflurane 1,2 and 3 minimum alveolar concentration （MAC）for 30 min,once or twice,with 15-min washout after each exposure.The slices were then subjected to 13-min OGD treatment（95%N2/5%CO2,glucose-free）,followed by 30-min reoxygenation.The population spikes（PSs）were recorded in the CA1 region of rat hippocampus.The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated,since it could indicate the recovery degree of neuronal function.In addition,to assess the role of mitogen-activated protein kinases（MAPKs）in preconditioning,U0126,an inhibitor of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）,and SB203580,an inhibitor of p38 MAPK,were separately added 10 min before sevoflurane exposure.Results Preconditioning once with sevoflurane 1,2,and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment,from（15.13±3.79）%（control）to（31.88±5.36）%, （44.00±5.01）%,and（49.50±6.25）%,respectively,and twice preconditioning with sevoflurane 1,2,and 3 MAC increased the percentage to（38.53±4.36）%,（50.74±7.05）%and（55.86±6.23）%,respectively.The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126[（16.23±4.62）%].Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro,and preconditioning twice enhances this effect.Besides,the activation of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）may be involved in this process.展开更多
基金supported by the Natural Science Fund of Fujian Province,No.2020J011058(to JK)the Project of Fujian Provincial Hospital for High-level Hospital Construction,No.2020HSJJ12(to JK)+1 种基金the Fujian Provincial Finance Department Special Fund,No.(2021)848(to FC)the Fujian Provincial Major Scientific and Technological Special Projects on Health,No.2022ZD01008(to FC).
文摘Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.
文摘We sincerely thank the authors of the commentary1 for their thoughtful analysis and constructive critique of our systematic review on ischemic preconditioning(IPC)and placebo effects in exercise capacity and athletic performance.2Their attention to methodological details,particularly concerning the inclusion and timing of warm-up protocols across studies,is commendable and contributes meaningfully to the ongoing refinement of IPC research in sports science.
文摘We highly commend Dr Souza et al.1for their systematic review research.The authors conducted a detailed investigation into the effects of ischemic preconditioning(IPC)on athletic performance,comparing it with placebo and no-intervention conditions.The study found that while IPC demonstrated superior effects over the no-intervention group in certain metrics(e.g.,time to exhaustion),its performance did not significantly surpass that of the placebo group.This suggests that the potential benefits of IPC may partially stem from participants’psychological expectations,or placebo effects.The study also highlighted the significant impact of placebo interventions on athletic performance,emphasizing the importance of distinguishing between placebo and no-intervention conditions in experimental designs.
基金supported by the National Natural Science Foundation of China(grant numbers 81371440,82271454 and 81971195).
文摘Objective Stroke is a main cause of disability and mortality worldwide.It has been reported that ischemic preconditioning(IP)has neuroprotective effects against stroke.This study aimed to verify the mechanism by which calcium-sensing recep-tor(Casr)inhibition-mediated M2 microglial transformation in the IP protects against stroke,which will provide a potential therapeutic target for stroke.Methods Middle cerebral artery occlusion(MCAO)rats and oxygen-glucose deprivation(OGD)neurons were used in this study.IP was induced via the transient MCAO and OGD methods.RNA sequencing(RNA-Seq)was used to explore the underlying key molecules.Western blotting and immunohistochemistry were performed to detect the expression of Casr and the M1 and M2 microglial markers.CCK8 was used to detect cell viability.The calcium concentration was detected via the use of Fluo-4 AM,a fluorescence probe.The Casr inhibitor NPS2143 and the Casr activator R568 were used to explore the role of Casr in M2 microglial transformation and neuroprotection.Results We first revealed that IP induced M2 microglial transformation in ischemic injury.In addition,MCAO injury increased Casr expression and the calcium concentration,which was inhibited by IP.Furthermore,Casr activation inhibited the M2 microglial transformation induced by IP.Finally,we found that Casr inhibition improved the survival rate,alleviated neurological deficits,and reduced the infarct volume induced by MCAO.Conclusions We confirmed that Casr-related neuroprotection induced by IP is associated with the transformation of M2 microglia.These findings can be used to understand the protective mechanisms of IP against ischemic stroke.
文摘Mesenchymal stem cells(MSCs)possess unique properties such as immunomodu-lation,paracrine actions,multilineage differentiation,and self-renewal.Therefore,MSC-based cell therapy is an innovative approach to treating various degenera-tive illnesses,including cardiovascular diseases.However,several challenges,including low transplant survival rates,low migration to the ischemic myocar-dium,and poor tissue retention,restrict the application of MSCs in clinical settings.These undesirable cell therapy outcomes mainly originated due to the overproduction of reactive oxygen species(ROS)in the injured heart.MSCs'stress-coping capacity can be enhanced by preconditioning them under conditions similar to the microenvironment of wounded tissues.Hydrogen peroxide(H_(2)O_(2))is a ROS that has been shown to activate protective cellular mechanisms such as survival,proliferation,migration,paracrine effects,and differentiation at suble-thal doses.These processes are induced via phosphatidylinositol 3-kinase/protein kinase B,p38 mitogen-activated protein kinases,c-Jun N-terminal kinase,Janus kinase/signal transducer and activator of the transcription,Notch1,and Wnt sig-naling pathways.H_(2)O_(2) preconditioning could lead to many clinical benefits,including ischemic injury reduction,enhanced survival of cellular transplants,and tissue regeneration.In this review,we present an overview of stem cell preconditioning methods and the biological functions activated by H_(2)O_(2) precondi-tioning.Furthermore,this review explores the molecular mechanisms underlying the protective cellular functions stimulated under H_(2)O_(2) preconditioning.
基金supported by the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(Grant No.2021QNLM020001)the National Key R&D Program of China(Grant No.2019YFC0605503C)+2 种基金the Major Scientific and Technological Projects of China National Petroleum Corporation(CNPC)(Grant No.ZD2019-183-003)the National Outstanding Youth Science Foundation(Grant No.41922028)the National Innovation Group Project(Grant No.41821002).
文摘Based on waveform fitting,full waveform inversion(FWI)is an important inversion method with the ability to reconstruct multi-parameter models in high precision.However,the strong nonlinear equation used in FWI presents the following challenges,such as low convergence efficiency,high dependence on the initial model,and the energy imbalance in deep region of the inverted model.To solve these inherent problems,we develop a timedomain elastic FWI method based on gradient preconditioning with the following details:(1)the limited memory Broyden Fletcher Goldfarb Shanno method with faster convergence is adopted to im-prove the inversion stability;(2)a multi-scaled inversion strategy is used to alleviate the nonlinear inversion instead of falling into the local minimum;(3)in addition,the pseudo-Hessian preconditioned illumination operator is involved for preconditioning the parameter gradients to improve the illumination equilibrium degree of deep structures.Based on the programming implementation of the new method,a deep depression model with five diffractors is used for testing.Compared with the conventional elastic FWI method,the technique proposed by this study has better effectiveness and accuracy on the inversion effect and con-vergence,respectively.
文摘In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary hypertension.Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured tissue.They also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell survival.Ferroptosis,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to cancer.The lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular structures.Understanding these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related diseases.This editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis pathway.Ferroptosis presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention.Further research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.
基金supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX)the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。
文摘Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.
文摘Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies,and pretreatment has proven to enhance cell vitality and function.In a recent publication,Li et al explored a new combination of pretreatment condi-tions.Here,we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.
基金the grants from the Department of Science and Technology of Jilin Province, China (No. 20070721)the Bureau of Science and Technology of Changchun, Jilin Province, China (No. 2007129).
文摘Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10- min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Results Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region （P 〈 0.01 vs 10-min ischemia group）. Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates（P〈0.01 vs 10-min ischemia group）.Conelusion Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.
基金supported by theScience Foundation of Shihezi University,Xinjiang Province,China(No.RCZX200688)
文摘Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually lead to different results.The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation（OGD）injury in vitro.Methods Rat hippocampal slices under normoxic conditions（95%O2/5%CO2）were pre-exposed to sevoflurane 1,2 and 3 minimum alveolar concentration （MAC）for 30 min,once or twice,with 15-min washout after each exposure.The slices were then subjected to 13-min OGD treatment（95%N2/5%CO2,glucose-free）,followed by 30-min reoxygenation.The population spikes（PSs）were recorded in the CA1 region of rat hippocampus.The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated,since it could indicate the recovery degree of neuronal function.In addition,to assess the role of mitogen-activated protein kinases（MAPKs）in preconditioning,U0126,an inhibitor of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）,and SB203580,an inhibitor of p38 MAPK,were separately added 10 min before sevoflurane exposure.Results Preconditioning once with sevoflurane 1,2,and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment,from（15.13±3.79）%（control）to（31.88±5.36）%, （44.00±5.01）%,and（49.50±6.25）%,respectively,and twice preconditioning with sevoflurane 1,2,and 3 MAC increased the percentage to（38.53±4.36）%,（50.74±7.05）%and（55.86±6.23）%,respectively.The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126[（16.23±4.62）%].Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro,and preconditioning twice enhances this effect.Besides,the activation of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）may be involved in this process.
