Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
OBJECTIVE:To find alternatives to natural musk,this study compared the pharmacological effects of cultivated musk,synthetic musk,and natural musk.The aim is to address the dual challenge of clinical demand for muskbas...OBJECTIVE:To find alternatives to natural musk,this study compared the pharmacological effects of cultivated musk,synthetic musk,and natural musk.The aim is to address the dual challenge of clinical demand for muskbased medicines and the endangered status of the musk deer population.METHODS:This study aimed to establish a rat model of acute cerebral ischemia/reperfusion injury(CI/RI)by creating a middle cerebral artery occlusion and reperfusion model.Methods including enzyme-linked immunosorbent assay kits,hematoxylin and eosin staining,Nissl staining,immunohistochemistry,and Western blot were employed to compare the extent of brain tissue damage,inflammatory factor levels,and platelet-related indicators in rats treated with musk from different sources(natural musk,cultivated musk,and synthetic musk),thereby evaluating their differences in neuroprotection.Analysis was performed using one-way analysis of variance.RESULTS:Results indicated that pretreatment with musk demonstrated a positive impact on neurological function by reducing cerebral infarction size,decreasing cerebral edema severity,increasing calcitonin gene related peptide levels,inhibiting 5-hydroxytryptamine release,and preserving the blood-brain barrier integrity.Notably,natural musk exhibited superior antithrombotic properties compared to cultivated and synthetic musk,primarily evidenced by its ability to inhibit platelet aggregation rate,improve cerebral blood perfusion,reduce platelet activating factor receptor protein expression,and lower thromboxane A2 levels.Cultivated musk was observed to elevate catalase and superoxide dismutase levels while concurrently dampening inducible nitric oxide synthase activity,thereby mitigating oxidative damage and also diminishing tumor necrosis factor-αand interleukin-1βcontents along with Glial fibrillary acidic protein expression,enhancing anti-inflammatory capacity.CONCLUSION:Musk sourced from diverse origins exhibits profound neuroprotective qualities against acute CI/RI in rats.Particularly,natural musk demonstrated a specific propensity towards reinforcing antithrombotic effects,whereas cultivated musk excelled in augmenting anti-inflammatory and antioxidative defenses,offering efficacious protection against acute CI/RI.The findings bolster the credibility of strategically employing diverse sources of musk as a preventive strategy against ischemic strokes.展开更多
Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean r...Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean region,was first introduced in China for acute IS treatment in 2004.NBP demonstrates multiple therapeutic actions,including reconstruction of microcirculation in the cerebral ischemia area,inhibition of platelet aggregation,reduction of cerebral infarction volume,maintenance of blood-brain barrier(BBB)integrity,and enhancement of cerebral blood perfusion.However,its overall efficacy remains moderate,limited by poor water solubility and low bioavailability,which constrains its clinical application.To address these limitations,researchers have actively pursued the development of NBP derivatives and analogs,achieving notable progress.These efforts,including substituent introduction,ring opening derivatization,esterification,and atom substitution,have generated diverse NBP derivatives.Several of these derivatives have advanced to clinical studies.Specifically,potassium 2-(1-hydroxypentyl)-benzoate(PHPB),brozopentyl sodium(BZP),and XY-03-EA(ZONK1103)have reached phase II clinical trials,while(S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt(AAPB)has received clinical trial approval for 2024.This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective,aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.展开更多
Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal var...Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.展开更多
Introduction.Ischemic stroke,spinal cord injury(SCI),and acute primary angle-closure glaucoma constitute three major clinically prevalent and highly disabling central nervous system(CNS)disorders.Their core pathogenes...Introduction.Ischemic stroke,spinal cord injury(SCI),and acute primary angle-closure glaucoma constitute three major clinically prevalent and highly disabling central nervous system(CNS)disorders.Their core pathogenesis universally originates from ischemia/reperfusion(I/R)injury affecting the cerebral,spinal cord,and/or retina.展开更多
Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active comp...Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.展开更多
Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways ...Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway.展开更多
Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein bet...Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.展开更多
Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necr...Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.展开更多
BACKGROUND Chronic mesenteric ischemia(CMI)is a rare but serious cause of postprandial abdominal pain and weight loss,often diagnosed late.CASE SUMMARY We report two cases with prolonged history of vague abdominal pai...BACKGROUND Chronic mesenteric ischemia(CMI)is a rare but serious cause of postprandial abdominal pain and weight loss,often diagnosed late.CASE SUMMARY We report two cases with prolonged history of vague abdominal pain,early satiety,and significant weight loss.Extensive workups for functional and structural gastrointestinal disorders were unrevealing.The diagnosis was ultimately prompted by gastroenterologist re-review of prior computed tomography abdomen studies—performed earlier during the investigation but not specifically targeting the mesenteric vasculature.On close inspection,both scans revealed extensive vascular calcifications involving the superior mesenteric and celiac arteries,which had not been mentioned in the original radiology reports.Subsequent dedicated vascular imaging confirmed significant mesenteric artery stenosis.Both patients underwent successful endovascular intervention with complete resolution of symptoms.CONCLUSION These cases highlight the importance of clinician-led image review and maintaining a high index of suspicion for CMI in elderly patients with unexplained gastrointestinal symptoms presenting to the gastroenterology department.展开更多
BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and proced...BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and procedural outcomes in PEVI.METHODS A prospective observational study was performed in 186 consecutive patients(65±12 years)at an academic medical center from January 2019 to April 2020(mean follow-up of 3.9±3.6 months)comparing the gender radiation disparity and outcomes of PEVI(n=147 underwent intervention,79.0%).Groups were divided into women(n=99,53.2%)and men(n=87,48.4%).Primary endpoints included air kerma,dose area product(DAP),fluoroscopy time,and contrast use.Secondary endpoints included all-cause mortality,acute myocardial infarction,acute kidney injury,stroke,repeat revascularization,major adverse limb event,and the composite of complications.RESULTS Men showed increased DAP compared with women(15221.2±25858.5µGy×m^(2) vs 9251.7±9555.3µGy×m^(2),P=0.047),but no significant difference in air kerma or any other primary endpoints.In the secondary endpoints,no significant diffe-rence was found between gender.CONCLUSION Men had increased DAP indicating more radiation absorption in the exposed area.Gender outcomes showed no difference in complications.Thus,PEVI can be safely performed in men or women.展开更多
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats wer...Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.展开更多
Objective MicroRNA-1(miR-1)aggravates myocardial ischemia–reperfusion(I/R)injury,whereas insulin-like growth factor-1(IGF-1)maintains cardiomyocyte homeostasis.In this study,the aim is to investigate whether miR-1 ca...Objective MicroRNA-1(miR-1)aggravates myocardial ischemia–reperfusion(I/R)injury,whereas insulin-like growth factor-1(IGF-1)maintains cardiomyocyte homeostasis.In this study,the aim is to investigate whether miR-1 can exacerbate I/R injury through the regulation of IGF-1.Methods The infarct area,lactate dehydrogenase,miR-1 level,and apoptosis level were examined in the Langendorff isolated rat I/R model.The hypoxia–reoxygenation model of rat cardiacmyocytes and H9c2 cells were developed to determine the levels of miR-1,IGF-1 mRNA,and IGF-1 protein.Furthermore,the dual-luciferase assay was used to verify the relationship between miR-1 and IGF-1.Results Overexpression of miR-1 increased the level of apoptosis and decreased the IGF-1 expression.However,inhibition of miR-1 expression decreased the level of apoptosis,alleviated the degree of injury,and increased the IGF-1 expression.Overexpression of IGF-1 also reduced the degree of cellular damage and level of apoptosis caused by the overexpression of miR-1.When IGF-1 was knocked down,myocardial cells displayed more severe damage and a higher apoptosis level,even with decreased levels of miR-1.Conclusion miR-1 promotes apoptosis and aggravates I/R injury by downregulating IGF-1.展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
Brain injuries like ischemic stroke induce endogenous stem cell production. Although the precise traits of stem cells in pathological brains remain unclear, we previously demonstrated that injury/ischemia-induced stem...Brain injuries like ischemic stroke induce endogenous stem cell production. Although the precise traits of stem cells in pathological brains remain unclear, we previously demonstrated that injury/ischemia-induced stem cells(iSCs)are present in the post-stroke mouse(Nakagomi et al.,2009)and human brains(Beppu et al.,2019).展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
BACKGROUND Acute mesenteric ischemia is a life-threatening disease.Intrasplenic gas is an extremely rare finding in such cases.CASE SUMMARY We report a case of a 79-year-old woman with a history of end-stage renal dis...BACKGROUND Acute mesenteric ischemia is a life-threatening disease.Intrasplenic gas is an extremely rare finding in such cases.CASE SUMMARY We report a case of a 79-year-old woman with a history of end-stage renal disease on hemodialysis for approximately 20 years,type 2 diabetes mellitus,and atrial fibrillation who presented with two days of epigastric pain.A computed tomography scan of the abdomen revealed intraperitoneal free air and significant intrasplenic gas.Laparoscopy revealed diffuse intestinal gangrene,and acute superior mesenteric ischemia was diagnosed.The patient died within 24 hours owing to profound shock.CONCLUSION Intrasplenic gas is an extremely rare finding on computed tomography imaging in cases of acute mesenteric ischemia.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
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金Supported by Key Project of National Natural Science Foundation of Sichuan:Research on the Mechanism of Detoxification and Synergistic Effects of Sichuan-Produced Toxic Authentic Medicinal Herbs Croton Seed and Aconite Root(No.2024NSFSC0054)National Interdisciplinary Innovation Team of Traditional Chinese Medicine:Multidisciplinary Innovation Team for Multidimensional Evaluation of Southwest Chinese Characteristic Traditional Chinese Medicine Resources(No.ZYYCXTD-D-202209)Sichuan Chinese Medicine Science and Technology Industry Innovation Team:Innovative Team for Multidimensional Evaluation and Product Development of Characteristic Traditional Chinese Medicine Resources(No.2022C001)。
文摘OBJECTIVE:To find alternatives to natural musk,this study compared the pharmacological effects of cultivated musk,synthetic musk,and natural musk.The aim is to address the dual challenge of clinical demand for muskbased medicines and the endangered status of the musk deer population.METHODS:This study aimed to establish a rat model of acute cerebral ischemia/reperfusion injury(CI/RI)by creating a middle cerebral artery occlusion and reperfusion model.Methods including enzyme-linked immunosorbent assay kits,hematoxylin and eosin staining,Nissl staining,immunohistochemistry,and Western blot were employed to compare the extent of brain tissue damage,inflammatory factor levels,and platelet-related indicators in rats treated with musk from different sources(natural musk,cultivated musk,and synthetic musk),thereby evaluating their differences in neuroprotection.Analysis was performed using one-way analysis of variance.RESULTS:Results indicated that pretreatment with musk demonstrated a positive impact on neurological function by reducing cerebral infarction size,decreasing cerebral edema severity,increasing calcitonin gene related peptide levels,inhibiting 5-hydroxytryptamine release,and preserving the blood-brain barrier integrity.Notably,natural musk exhibited superior antithrombotic properties compared to cultivated and synthetic musk,primarily evidenced by its ability to inhibit platelet aggregation rate,improve cerebral blood perfusion,reduce platelet activating factor receptor protein expression,and lower thromboxane A2 levels.Cultivated musk was observed to elevate catalase and superoxide dismutase levels while concurrently dampening inducible nitric oxide synthase activity,thereby mitigating oxidative damage and also diminishing tumor necrosis factor-αand interleukin-1βcontents along with Glial fibrillary acidic protein expression,enhancing anti-inflammatory capacity.CONCLUSION:Musk sourced from diverse origins exhibits profound neuroprotective qualities against acute CI/RI in rats.Particularly,natural musk demonstrated a specific propensity towards reinforcing antithrombotic effects,whereas cultivated musk excelled in augmenting anti-inflammatory and antioxidative defenses,offering efficacious protection against acute CI/RI.The findings bolster the credibility of strategically employing diverse sources of musk as a preventive strategy against ischemic strokes.
基金supported by the National Natural Science Foundation of China(Nos.21977058 and 82473840)the Key R&D Program of Jiangsu Province(No.BE2021677)+2 种基金China Postdoctoral Science Foundation(No.2018T110533)the Key Natural Science Foundation of Jiangsu Higher Education Institutions(No.20KJA350002)Jiangsu Province Innovation Project of Postgraduate Training(No.KYCX22_3380).
文摘Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean region,was first introduced in China for acute IS treatment in 2004.NBP demonstrates multiple therapeutic actions,including reconstruction of microcirculation in the cerebral ischemia area,inhibition of platelet aggregation,reduction of cerebral infarction volume,maintenance of blood-brain barrier(BBB)integrity,and enhancement of cerebral blood perfusion.However,its overall efficacy remains moderate,limited by poor water solubility and low bioavailability,which constrains its clinical application.To address these limitations,researchers have actively pursued the development of NBP derivatives and analogs,achieving notable progress.These efforts,including substituent introduction,ring opening derivatization,esterification,and atom substitution,have generated diverse NBP derivatives.Several of these derivatives have advanced to clinical studies.Specifically,potassium 2-(1-hydroxypentyl)-benzoate(PHPB),brozopentyl sodium(BZP),and XY-03-EA(ZONK1103)have reached phase II clinical trials,while(S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt(AAPB)has received clinical trial approval for 2024.This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective,aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.
基金supported by the National Natural Science Foundation of China(82250410380 and 62171101)the Natural Science Foundation of Sichuan Province(24NSFSC6257)the China MOST2030 Brain Project(2022ZD0208500).
文摘Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.
基金supported by the National Natural Science Foundation of China(Grant nos.62576136 to Yan Huang82372507,82572869 to Kun Xiongthe National Natural Science Foundation of Hunan Province(Grant no.2026JJ30177).
文摘Introduction.Ischemic stroke,spinal cord injury(SCI),and acute primary angle-closure glaucoma constitute three major clinically prevalent and highly disabling central nervous system(CNS)disorders.Their core pathogenesis universally originates from ischemia/reperfusion(I/R)injury affecting the cerebral,spinal cord,and/or retina.
基金supported by the study on the material basis and mechanism of action of American ginseng in the treatment of myocardial ischaemia comorbid depression(2024JH2/102500059).
文摘Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.
基金supported by the Foundation Project:National Natural Science.Foundation of China(Nos.:82460249,82100417,81760094)The Foundation of Jiangxi Provincial Department of Science and Technology Outstanding Youth Fund Project(20212BAB206022,20242BAB23080).
文摘Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway.
基金“Dawn”Program of Shanghai Education Commission,No.22SG37(to PY)the National Natural Science Foundation of China,Nos.82371313(to PY),82401536(to YongxinZ).
文摘Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.
基金Shanghai Rehabilitation Medical Association,Grant/Award Number:2023JGKT24China Rehabilitation Medical Association,Grant/Award Number:KFKT-2023Shanghai“14th Five-Year Plan”Traditional Chinese Medicine Specialty and Traditional Chinese Medicine Emergency Capacity Improvement Project,Grant/Award Number:ZYTSZK2-7。
文摘Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.
文摘BACKGROUND Chronic mesenteric ischemia(CMI)is a rare but serious cause of postprandial abdominal pain and weight loss,often diagnosed late.CASE SUMMARY We report two cases with prolonged history of vague abdominal pain,early satiety,and significant weight loss.Extensive workups for functional and structural gastrointestinal disorders were unrevealing.The diagnosis was ultimately prompted by gastroenterologist re-review of prior computed tomography abdomen studies—performed earlier during the investigation but not specifically targeting the mesenteric vasculature.On close inspection,both scans revealed extensive vascular calcifications involving the superior mesenteric and celiac arteries,which had not been mentioned in the original radiology reports.Subsequent dedicated vascular imaging confirmed significant mesenteric artery stenosis.Both patients underwent successful endovascular intervention with complete resolution of symptoms.CONCLUSION These cases highlight the importance of clinician-led image review and maintaining a high index of suspicion for CMI in elderly patients with unexplained gastrointestinal symptoms presenting to the gastroenterology department.
文摘BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and procedural outcomes in PEVI.METHODS A prospective observational study was performed in 186 consecutive patients(65±12 years)at an academic medical center from January 2019 to April 2020(mean follow-up of 3.9±3.6 months)comparing the gender radiation disparity and outcomes of PEVI(n=147 underwent intervention,79.0%).Groups were divided into women(n=99,53.2%)and men(n=87,48.4%).Primary endpoints included air kerma,dose area product(DAP),fluoroscopy time,and contrast use.Secondary endpoints included all-cause mortality,acute myocardial infarction,acute kidney injury,stroke,repeat revascularization,major adverse limb event,and the composite of complications.RESULTS Men showed increased DAP compared with women(15221.2±25858.5µGy×m^(2) vs 9251.7±9555.3µGy×m^(2),P=0.047),but no significant difference in air kerma or any other primary endpoints.In the secondary endpoints,no significant diffe-rence was found between gender.CONCLUSION Men had increased DAP indicating more radiation absorption in the exposed area.Gender outcomes showed no difference in complications.Thus,PEVI can be safely performed in men or women.
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
基金sponsored by Shandong Provincial Key Research and Development Program(Major Technological Innovation Project)([2021]CXGC010508)Guizhou Province Youth Science and Technology Talent Plan(YQK[2023]038)+1 种基金Science and Technology Department of Zunyi City of Guizhou province of China([2020]7)Key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302).
文摘Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.
基金supported by the National Natural Science Foundation of China(81473453,81673800)the Projects of International Science and Technology Cooperation in Henan(182102410084).
文摘Objective MicroRNA-1(miR-1)aggravates myocardial ischemia–reperfusion(I/R)injury,whereas insulin-like growth factor-1(IGF-1)maintains cardiomyocyte homeostasis.In this study,the aim is to investigate whether miR-1 can exacerbate I/R injury through the regulation of IGF-1.Methods The infarct area,lactate dehydrogenase,miR-1 level,and apoptosis level were examined in the Langendorff isolated rat I/R model.The hypoxia–reoxygenation model of rat cardiacmyocytes and H9c2 cells were developed to determine the levels of miR-1,IGF-1 mRNA,and IGF-1 protein.Furthermore,the dual-luciferase assay was used to verify the relationship between miR-1 and IGF-1.Results Overexpression of miR-1 increased the level of apoptosis and decreased the IGF-1 expression.However,inhibition of miR-1 expression decreased the level of apoptosis,alleviated the degree of injury,and increased the IGF-1 expression.Overexpression of IGF-1 also reduced the degree of cellular damage and level of apoptosis caused by the overexpression of miR-1.When IGF-1 was knocked down,myocardial cells displayed more severe damage and a higher apoptosis level,even with decreased levels of miR-1.Conclusion miR-1 promotes apoptosis and aggravates I/R injury by downregulating IGF-1.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
基金partially supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (15K0672318K07380)the Japan Agency for Medical Research and Development (AMED) (21nk0101538h0002) (to TN)。
文摘Brain injuries like ischemic stroke induce endogenous stem cell production. Although the precise traits of stem cells in pathological brains remain unclear, we previously demonstrated that injury/ischemia-induced stem cells(iSCs)are present in the post-stroke mouse(Nakagomi et al.,2009)and human brains(Beppu et al.,2019).
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘BACKGROUND Acute mesenteric ischemia is a life-threatening disease.Intrasplenic gas is an extremely rare finding in such cases.CASE SUMMARY We report a case of a 79-year-old woman with a history of end-stage renal disease on hemodialysis for approximately 20 years,type 2 diabetes mellitus,and atrial fibrillation who presented with two days of epigastric pain.A computed tomography scan of the abdomen revealed intraperitoneal free air and significant intrasplenic gas.Laparoscopy revealed diffuse intestinal gangrene,and acute superior mesenteric ischemia was diagnosed.The patient died within 24 hours owing to profound shock.CONCLUSION Intrasplenic gas is an extremely rare finding on computed tomography imaging in cases of acute mesenteric ischemia.
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.
