The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
Ischemia-reperfusion injury(IRI)remains an unavoidable challenge in liver surgery,with macrophages playing a critical role in its pathogenesis.However,the mechanisms by which macrophages regulate the pathogenesis of I...Ischemia-reperfusion injury(IRI)remains an unavoidable challenge in liver surgery,with macrophages playing a critical role in its pathogenesis.However,the mechanisms by which macrophages regulate the pathogenesis of IRI are not well understood.Through a target-guided screening approach,we identified a small 3 k Da peptide(Sj DX5-271)from various schistosome egg-derived peptides that induced M2 macrophage polarization.SjDX5-271 treatment protected mice against liver IRI by promoting M2 macrophage polarization,and this protective effect was abrogated when the macrophages were depleted.Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages from the SjDX5-271 treatment group.We further identified that SjDX5-271 promoted M2 macrophage polarization by inhibiting the TLR4/My D88/NF-κB signaling pathway and alleviated hepatic inflammation in liver IRI.Collectively,SjDX5-271 exhibited some promising therapeutic effects in IRI and represented a novel therapeutic approach,potentially applicable to other immune-related diseases.The current study demonstrates the potential of new biologics from the parasite,enhances our understanding of host-parasite interplay,and provides a blueprint for future therapies for immunerelated diseases.展开更多
With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but i...With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but ischemic brain tissues still face ischemia-reperfusion injury after recanalization. Nowadays, effective neurological protective agents still cannot completely resist the multiple damages of ischemia-reperfusion injury. As an iron-dependent mode of programmed cell death, ferroptosis occupies an important position in ischemia-reperfusion injury. Selenium plays a unique protective role in ischemia-reperfusion injury as an active site element in the center of glutathione peroxidase. Therefore, the study mainly aims to review the protective role of selenium in IS and the related mechanisms, as well as the effect of selenium on the risk factors of IS.展开更多
Intestinal ischemia-reperfusion injury(IIRI)is a complex and severe pathophysiological process characterized by oxidative stress,inflammation,and apoptosis.In recent years,the critical roles of extracellular matrix(EC...Intestinal ischemia-reperfusion injury(IIRI)is a complex and severe pathophysiological process characterized by oxidative stress,inflammation,and apoptosis.In recent years,the critical roles of extracellular matrix(ECM)genes and microRNAs(miRNAs)in IIRI have garnered widespread attention.This review aims to systematically summarize the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI.First,we review the molecular mechanisms of IIRI,focusing on the dual role of the ECM in tissue injury and repair processes.The expression changes and functions of ECM components such as collagen,elastin,and matrix metalloproteinases during IIRI progression are deeply analyzed.Second,we systematically summarize the regulatory roles of miRNAs in IIRI,particularly the mechanisms and functions of miRNAs such as miR-125b and miR-200a in regulating inflammation,apoptosis,and ECM remodeling.Additionally,this review discusses potential diagnostic biomarkers and treatment strategies based on ECM genes and miRNAs.We extensively evaluate the prospects of miRNA-targeted therapy and ECM component modulation in preventing and treating IIRI,emphasizing the clinical translational potential of these emerging therapies.In conclusion,the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI provides new directions for further research,necessitating additional clinical and basic studies to validate and expand these findings for improving clinical outcomes in IIRI patients.展开更多
Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)funct...Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.展开更多
Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate w...Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.展开更多
AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through an...AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for 7d.After 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were measured.RESULTS:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model group.Caspase-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model group.Caspase-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model.CONCLUSION:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model.展开更多
Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage ...Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.展开更多
BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whet...BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.展开更多
[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were ran...[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.展开更多
Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While th...Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While these methods enhance tissue perfusion in the ischemic penumbra,they also trigger complex neurotoxic reactions,including apoptosis,acidosis,ion imbalance,oxidative stress,and pyroptosis,exacerbating cerebral ischemia-reperfusion injury(CIRI).Pyroptosis,a recently discovered form of programmed cell death driven by inflammation,plays a significant role in neuronal death during CIRI.This study reviews the regulatory mechanisms of pyroptosis in CIRI.展开更多
Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations ...Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway.展开更多
Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reper...Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.展开更多
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China(Grant No.81971965)。
文摘Ischemia-reperfusion injury(IRI)remains an unavoidable challenge in liver surgery,with macrophages playing a critical role in its pathogenesis.However,the mechanisms by which macrophages regulate the pathogenesis of IRI are not well understood.Through a target-guided screening approach,we identified a small 3 k Da peptide(Sj DX5-271)from various schistosome egg-derived peptides that induced M2 macrophage polarization.SjDX5-271 treatment protected mice against liver IRI by promoting M2 macrophage polarization,and this protective effect was abrogated when the macrophages were depleted.Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages from the SjDX5-271 treatment group.We further identified that SjDX5-271 promoted M2 macrophage polarization by inhibiting the TLR4/My D88/NF-κB signaling pathway and alleviated hepatic inflammation in liver IRI.Collectively,SjDX5-271 exhibited some promising therapeutic effects in IRI and represented a novel therapeutic approach,potentially applicable to other immune-related diseases.The current study demonstrates the potential of new biologics from the parasite,enhances our understanding of host-parasite interplay,and provides a blueprint for future therapies for immunerelated diseases.
文摘With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but ischemic brain tissues still face ischemia-reperfusion injury after recanalization. Nowadays, effective neurological protective agents still cannot completely resist the multiple damages of ischemia-reperfusion injury. As an iron-dependent mode of programmed cell death, ferroptosis occupies an important position in ischemia-reperfusion injury. Selenium plays a unique protective role in ischemia-reperfusion injury as an active site element in the center of glutathione peroxidase. Therefore, the study mainly aims to review the protective role of selenium in IS and the related mechanisms, as well as the effect of selenium on the risk factors of IS.
基金Supported by Health Science and Technology Programme of Zhejiang Province,No.2022KY1391.
文摘Intestinal ischemia-reperfusion injury(IIRI)is a complex and severe pathophysiological process characterized by oxidative stress,inflammation,and apoptosis.In recent years,the critical roles of extracellular matrix(ECM)genes and microRNAs(miRNAs)in IIRI have garnered widespread attention.This review aims to systematically summarize the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI.First,we review the molecular mechanisms of IIRI,focusing on the dual role of the ECM in tissue injury and repair processes.The expression changes and functions of ECM components such as collagen,elastin,and matrix metalloproteinases during IIRI progression are deeply analyzed.Second,we systematically summarize the regulatory roles of miRNAs in IIRI,particularly the mechanisms and functions of miRNAs such as miR-125b and miR-200a in regulating inflammation,apoptosis,and ECM remodeling.Additionally,this review discusses potential diagnostic biomarkers and treatment strategies based on ECM genes and miRNAs.We extensively evaluate the prospects of miRNA-targeted therapy and ECM component modulation in preventing and treating IIRI,emphasizing the clinical translational potential of these emerging therapies.In conclusion,the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI provides new directions for further research,necessitating additional clinical and basic studies to validate and expand these findings for improving clinical outcomes in IIRI patients.
基金supported by grants from the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0148)the National Natural Science Foundation of China (82170666 and 81873592)Chongqing Research Program of Technological Innovation and Application Demonstration (cstc2021jscx-gksbX0060)
文摘Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81970563)the Medical Health Science and Technology Project of Health Commission of Zhejiang Province(2019RC055).
文摘Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.
基金Supported by the National Natural Science Foundation of China(No.82174444)the Chengdu University of Traditional Chinese Medicine Xinglin Scholar Discipline Talent Research Promotion Program Project(No.XKTD2022009)the Inheritance and Communication Department of Science and Technology Innovation Engineering Department of Chinese Academy of Chinese Medical Sciences(No.XJ2023001701).
文摘AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for 7d.After 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were measured.RESULTS:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model group.Caspase-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model group.Caspase-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model.CONCLUSION:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model.
基金Supported by Key Project of Henan Provincial Administration of Traditional Chinese Medicine,No.2017ZY1020General Public Relations Project of Henan Provincial Department of Science and Technology,No.212102311123General Research Project of the National Administration of Traditional Chinese Medicine,No.GZY-KJS-2021-017.
文摘Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.
基金Supported by the National Natural Science Foundation of China,No.82200270.
文摘BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.
文摘[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.
文摘Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While these methods enhance tissue perfusion in the ischemic penumbra,they also trigger complex neurotoxic reactions,including apoptosis,acidosis,ion imbalance,oxidative stress,and pyroptosis,exacerbating cerebral ischemia-reperfusion injury(CIRI).Pyroptosis,a recently discovered form of programmed cell death driven by inflammation,plays a significant role in neuronal death during CIRI.This study reviews the regulatory mechanisms of pyroptosis in CIRI.
基金supported by the S&T Program of Xingtai(2023ZC178).
文摘Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway.
基金supported fiancially by the Natural Science Foundation of Inner Mongolia Autonomous Region in China(Grant No.2018MS08043)Inner Mongolia Autonomous Region Scientific and Technological Achievements Transformation Guidance Project in China(2020PT0030).
文摘Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.
