Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

Guicao Baidu decoction in mitigating chemotherapy-induced myocardial injury:case report and mechanism investigation

To observe the effects of GuiCaoBaiDu Decoction(GCBD)on chemotherapy especially doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC)and explore the mechanisms.The present study presents a case demonstrating the preventive and therapeutic effects of GCBD on myocardial injury following chemotherapy.Then network pharmacology was employed to predict the targets of GCBD.Subsequently,a DOX-induced apoptosis model of H9C2 cardiomyocytes was established and co-cultured with serum containing GCBD serum.The viability and myocardial enzyme levels were evaluated using CCK8 assay and ELISA assay,TUNEL was using for apoptosis test.The GCBD effect was confirmed by tests of ROS andα-actinin levels,evaluation of mitochondrial morphology,and BAX co-localization with mitochondria.Furthermore,the expression levels of apoptosis-related molecules were determined via Western blotting.Additionally,a mouse model exhibiting DOX-induced cardiac functional impairment was generated and subsequently treated with GCBD.Myocardial enzyme level was tested at first,then echocardiography was tested,myocardial apoptosis in mice was observed through HE staining while related proteins were detected using IHC.Network pharmacological analyses revealed that GCBD exerts its effects on BAX,Caspase7,and other related molecules.Initially,we demonstrated the effective amelioration of DIC in cardiomyocyte viability,LDH/CK levels,α-actinin and ROS levels,and apoptosis by GCBD through improvements in TUNEL test,mitochondrial morphology and WB.The efficacy of GCBD in enhancing cardiac function in DIC mice has been validated through animal experiments.Taken together,our study showed that GCBD could significantly alleviate DOX induced myocardial injury by regulating mitochondrial apoptosis.The utilization of GCBD can effectively contribute to the prevention and treatment of chemotherapy-induced myocardial injury when anthracycline chemotherapy is employed in clinical practice.

The Predictive Value of NLR, IL-6, CRP, and PCT in Mycoplasmal Pneumonia with Complicated Myocardial Injury

Objective:To evaluate the dynamic changes in neutrophil-to-lymphocyte ratio(NLR),interleukin-6(IL-6),C-reactive protein(CRP),and procalcitonin(PCT)levels in children with Mycoplasma pneumoniae pneumonia(MPP)complicated by myocardial injury and to determine their predictive value both individually and in combination.Methods:150 children diagnosed with MPP at Jiujiang Maternal and Child Health Hospital between June 2023 and June 2024 were selected.Patients were divided into the myocardial damage group(MD group,n=65)and the non-myocardial damage group(non-MD group,n=85),based on the presence of myocardial injury.Ninety hospitalized children without MPP served as the control group(Con group).Myocardial enzyme profile indicators,including lactate dehydrogenase(LDH),α-hydroxybutyrate dehydrogenase(α-HBDH),aspartate aminotransferase(AST),high-sensitivity cardiac troponin I(hs-cTnI),creatine kinase(CK),and creatine kinase-MB(CK-MB),were measured using a chemiluminescent immunoassay analyzer.Serum NLR,IL-6,CRP,and PCT levels were determined using appropriate analyzers.The correlation between these markers and myocardial enzyme indicators was analyzed using Spearman correlation analysis.Multivariate logistic regression was applied to identify risk factors for myocardial injury in MPP patients.Results:Serum levels of NLR,IL-6,CRP,and PCT in the MD and non-MD groups were significantly higher than in the Con group(P<0.05),with the MD group showing higher levels than the non-MD group(P<0.05).These markers were positively correlated with myocardial enzyme indicators.Logistic regression identified elevated NLR,IL-6,CRP,PCT,LDH,α-HBDH,AST,hs-cTnI,CK,and CK-MB as risk factors for myocardial injury in MPP patients(P<0.05).Conclusion:Elevated levels of NLR,IL-6,CRP,PCT,and myocardial enzymes are significant risk factors for myocardial injury in children with MPP,offering valuable insights for prevention and prognosis.

Mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury based on network pharmacology and molecular docking techniques

The objective of this work was to investigate the mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury.In the present study,Balanophora involucrata was extracted by refluxing 75%of ethanol.The obtained extract was extracted with petroleum ether,ethyl acetate and n-butanol respectively.And the ethyl acetate layer was separated.The extract was prepared by silica gel column chromatography,sephadex LH-20 elution and thin layer chromatography.After that,the Swiss target prediction database was utilized to obtain the targets of Balanophora involucrata,and the Genecards,OMIM and TTD databases were used to predict and screen the targets of Balanophora involucrata for the treatment of myocardial injury.The active ingredient-target network was constructed using Cytoscape software,and the PPI network was mapped using String database and Cytoscape software.GO bioprocess enrichment analysis and KEGG pathway enrichment analysis were performed by Metascape software to predict the mechanism of action.Molecular docking was performed in Discovery Studio 2016 client software to verify the binding of Balanophora involucrata polyphenols to key targets.In this study,six polyphenolic compounds were isolated from Balanophora involucrata.By GO enrichment analysis,1614 biological processes(BP),127 cellular compositions(CC),and 215 molecular functions(MF)were obtained;a total of 155 cross-targets were involved in the KEGG enrichment analysis.The PPI network showed that quercetin was the main active component of polyphenolic compounds against myocardial injury and that AKT1,EGFR,STAT3,SRC,ESR1,MMP9,HSP90AA1 and other related signals were associated with myocardial injury treatment.Finally,the multi-component-multi-target-multi-pathway action of Balanophora involucrata was concluded,which provided new ideas and methods for further research on the mechanism of action of Balanophora involucrata in myocardial injury.

L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenol-induced cardiac hypertrophy

Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.

Effects of Continuous Non-Invasive Blood Pressure Monitoring on Intraoperative Hemodynamics and Postoperative Myocardial Injury in Craniotomy:Comparison Between Groups Based on Self-Control and Propensity Score Matching

Objective:To explore the effect of continuous non-invasive blood pressure monitoring on intraoperative hemodynamics and postoperative myocardial injury in craniotomy.Methods:120 cases of elective craniotomy were divided into the self-control group(continuous non-invasive blood pressure monitoring and intermittent cuff non-invasive blood pressure monitoring,CNAP group)and propensity score matching group(only intermittent cuff non-invasive blood pressure measurement in previous craniotomy,PSM group);Goal-directed hemodynamic management in CNAP group included heart rate(HR),blood pressure(BP),stroke volume(SV),stroke variability(SVV),and systemic vascular resistance index(SVRI).The main index is to compare the troponin level within 72 hours after operation between the CNAP group and the PSM group;The secondary indicators are the comparison of the hemodynamic conditions between the CNAP group and the PSM at 10 specific time points.Results:The incidence of postoperative myocardial injury in the CNAP group was significantly lower than that in the PSM group(12%vs.30%,P=0.01);in the CNAP group hypotensive episodes(6 vs.3,P=0.01),positive balance of fluid therapy(700 vs.500 mL,P<0.001),more use of vasoactive drugs(29 vs.18,P=0.04),more stable hemodynamics medical status(P=0.03)were recorded.Conclusion:The hemodynamic management strategy based on continuous non-invasive blood pressure monitoring can reduce the incidence of myocardial injury after elective craniotomy and maintain a more stable hemodynamic state.

Diagnostic and prognostic value of minor elevated cardiac troponin levels for percutaneous coronary intervention-related myocardial injury:a prospective,single-center and double-blind study

Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT （cTns） in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events （MACEs）. Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit （URL） in 133 （13.2%） patients, among which 22 （2.2%） were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 （P = 0.33, 95% CI： 0.74-2.46）. In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.

Abdominal paracentesis drainage ameliorates myocardial injury in severe experimental pancreatitis rats through suppressing oxidative stress

BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODS SAP was induced by 5%sodium taurocholate retrograde injection in Sprague-Dawley rats.APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction.Morphological staining,serum amylase and inflammatory mediators,serum and ascites high mobility group box(HMGB)1,cardiac-related enzymes indexes and cardiac function,oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats.Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTS APD treatment improved cardiac morphological changes,inhibited cardiac dysfunction,decreased cardiac enzymes and reduced cardiomyocyte apoptosis,proapoptotic Bax and cleaved caspase-3 protein levels.APD significantly decreased serum levels of HMGB1,inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury.Furthermore,the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress,which may be a novel mechanism behind the effectiveness of APD on SAP.

Cardioprotective effect of erythropoietin on sepsisinduced myocardial injury in rats

BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.

Relationship Between Myocardial Injury and Expression of PGC-1α and Its Coactivators in Chronic Keshan Disease

Objective:Keshan disease(KD)is a mitochondrial cardiomyopathy.The present study explored the roles of peroxisome proliferator-activated receptor(PPAR)-y coactivator-la(PGC-la),the key regulator of mitochondrial structure and function,and its coactivators in myocardial injury in chronic KD.Furthermore,the usefulness of these molecules in the diagnosis of chronic KD was assessed.

Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation

Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation group(S group,n=6),ventricular fibrillation control group(VF-C group,n=8)and 654-1 intervention group(VF-I group,n=8).Hemodynamics was recorded at baseline,at recovery of spontaneous circulation(ROSC),and 1 h,2 h,4h and 6 h thereafter.Sidestream dark field(SDF)technology was used to evaluate and monitor the microcirculation flow index,total vessel density,perfusion vessel ratio,De-Backer score,and perfusion vessel density in animal viscera at various time points.Results After administration of 654-1 at 1.5 h post-ROSC,the hemodynamics in the VF-I group,as compared with the VF-C group,was significantly improved.The visceral microcirculation detected by SDF was also significantly improved in the VF-I group.As observed through electron microscopy,significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.Conclusion Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Effects and mechanisms of glucose-insulin-potassium on post-procedural myocardial injury after percutaneous coronary intervention

Objective To evaluate the effects and mechanisms of glucose-insulin-potassium(GIK)on post-procedural myocardial injury(PMI)after percutaneous coronary intervention(PCI).Methods A total of 200 non-diabetic patients with documented coronary heart disease(CHD)were divided into the Group GIK and Group G,with 100 patients in each group.Patients in Group G were given intravenous infusion of glucose solution 2 hours before PCI.As compared,patients in Group GIK were given GIK.Results Both post-procedural creatine phosphokinase isoenzyme MB(CK-MB;62.1±47.8 vs.48.8±52.6 U/L,P=0.007)and cTnI(0.68±0.83 vs.0.19±0.24 ng/mL,P<0.001)in Group GIK were significantly higher than those in Group G.In Group G,9.0%and 4.0%of patients had post-procedural increases in CK-MB 1-3 times and>3 times,which were significantly lower than those in Group GIK(14.0%and 7.0%,respectively;all P values<0.01);13.0%and 7.0%of patients had post-procedural increases in cTnI 1-3 times and>3 times,which were also significantly lower than those in Group GIK(21.0%and 13.0%,respectively;all P<0.001).Pre-procedural(10.2±4.5 vs.5.1±6.3,P<0.001)and post-procedural rapid blood glucose(RBG)levels(8.9±3.9 vs.5.3±5.6,P<0.001)in Group G were higher than those in Group GIK.In adjusted logistic models,usage of GIK(compared with glucose solution)remained significantly and independently associated with higher risk of post-procedural increases in both CK-MB and cTnI levels>3 times.Furthermore,pre-procedural RBG levels<5.0mmol/L were significantly associated with higher risk of post-procedural increases in both CK-MB and cTnI levels.Conclusions In non-diabetic patients with CHD,the administration of GIK may increase the risk of PMI due to hypoglycemia induced by GIK.

Acute myocardial injury in patients with COVID-19:Possible mechanisms and clinical implications

Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs,but also the cardiovascular system,having a major impact on patients’outcomes.Myocardial injury(MI)occurs in the context of coronavirus infectious disease 2019(COVID-19)and is associated with a higher risk of severe clinical outcome and mortality.COVID-19-related MI can have various clinical manifestations,of which the main ones are myocarditis,stress cardiomyopathy,acute coronary syndrome,and pulmonary embolism.The exact mechanisms of how MI occurs in these patients are not yet fully known.Direct injury,through direct viral myocardial invasion,and indirect injury,through interaction with angiotensin I converting enzyme 2,increased inflammation,and thrombocyte and endothelial dysfunction,could be involved in acute MI in patients with COVID-19.A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies.The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.

Resveratrol ameliorates diabetic myocardial injury through HSF1-mediated ferroptosis

Objective:To observe the effect of resveratrol on the injury of diabetic cardiomyocytes and its effect on HSF1 mediated iron death.Methods:the diabetic cardiomyopathy model was established by high glucose induced H9c2,and H9c2 was exposed to normal glucose concentration as a control.Then the intervention was performed with the corresponding drugs.The cell proliferation level was detected by CCK8 method,the concentrations of LDH,SOD,MDA and iron ions were detected by kit method,and the expression levels of HSF1,apoptotic proteins(Bax and Bcl-2)and iron death marker proteins(ACSL4,GPX4 and SLC7A11)were detected by Western blot;Results:compared with the blank group,the cell activity,SOD activity,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein in the model group decreased significantly,and the LDH activity,MDA content,Bax and ACSL4 protein expression,Bax/Bcl-2 ratio and Fe^(2+)content increased significantly(P<0.01).Compared with the model group,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein increased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)decreased significantly in the resveratrol group(P<0.01).After the intervention,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein decreased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)increased significantly in si-hsf1 group(P<0.01);Conclusion:resveratrol can inhibit cell iron death and improve high glucose induced cardiomyocyte injury by up regulating the expression of HSF1.

BH3-only protein Bim is involved in myocardial injury induced by co-stress of ischemia and cold stress in rats

Objectives To investigate the effect of co-exposure of myocardial ischemia and cold stress on myocardial injury in rats and the relative mechanism.Methods Myocardial ischemia model was established by ligation of left coronary artery.SD rats were randomly allocated to 4 groups; sham+normal temperature(S group),sham+cold stress(SC group),myocardial ischemia+ normal temperature(Ⅰgroup), myocardial ischemia+cold stress(IC group).On the condition of 26℃,SC and IC groups were keeped in a 4℃artificial chamber for 8h(8;00-16:00) for 4 consecu- tive days.Car diac function was assessed by echocardiography;pathological change was analyzed by HE staining;myocardial infarct size was determined by TTC staining;Bim,Caspase-3 expression in myocardium was determined by western blotting.Results It was demonstrated that co-exposure of myocardial ischemia and cold stress could significantly make the cardiac muscle in abnormal shape,increase the infarct size and the expression of Bim and Caspase-3.Conclusions Co-exposure of myocardial ischemia and cold stress may aggravate the cardiac injury,pro- apoptosis protein Bim is involved.

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism:A case-control study

Background:The potential impact of pre-existing coronary artery stenosis(CAS)on acute pulmonary embolism(PE)episodes remains underexplored.This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I(hs-cTnI)levels in patients with PE.Methods:In this multicenter,prospective case-control study,88 cases and 163 controls matched for age,sex,and study center were enrolled.Cases were patients with PE with elevated hs-cTnI.Controls were patients with PE with normal hs-cTnI.Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography.CAS was defined as≥50%stenosis of the lumen diameter in any coronary vessel>2.0 mm in diameter.Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results:The percentage of CAS was higher in the case group compared to the control group(44.3%[39/88]vs.30.1%[49/163];P=0.024).In multivariable conditional logistic regression model 1,CAS(adjusted odds ratio[OR],2.680;95%confidence interval[CI],1.243-5.779),heart rate>75 beats/min(OR,2.306;95%CI,1.056-5.036)and N-terminal pro-B type natriuretic peptide(NT-proBNP)>420 pg/mL(OR,12.169;95%CI,4.792-30.900)were independently associated with elevated hs-cTnI.In model 2,right CAS(OR,3.615;95%CI,1.467-8.909)and NT-proBNP>420 pg/mL(OR,13.890;95%CI,5.288-36.484)were independently associated with elevated hs-cTnI.Conclusions:CAS was independently associated with myocardial injury in patients with PE.Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Effect of Catechins on Myocardial Injury and Inflammatory Factors in Rats with Coronary Heart Disease under PI3K/Akt/eNOS Signaling Pathway

Objective:To discuss the effect of catechins on myocardial injury and inflammatory factors in rats with coronary heart disease under PI3K/Akt/eNOS signaling pathway.Methods:A total of 50 healthy adult pathogen-free(SPF)-grade SD rats were divided into five groups by random number table method.Except for the blank group,the other four groups were fed with high fat to construct a rat model of coronary artery disease.After the model was successfully constructed,the blank group and the model group were given saline by gavage,the positive group was given 25 mg/kg aspirin by gavage,the low-dose group was given 20 mg/kg catechin by gavage,and the high-dose group was given 60 mg/kg catechin by gavage.The expression levels of PI3K/Akt/eNOS signaling pathway-related proteins,myocardial injury markers,myocardial infarction and myocardial inflammatory factors were observed and compared in the five groups.Results:Overall,there were significant differences in the expression levels of PI3K,p-Akt/Akt,and p-eNOS/eNOS in the five groups of rats(P<0.05);there were significant differences in the expression levels of CK-MB and c Tn I in the five groups of rats(P<0.05);there were significant differences in ischemic area,infarct area,and myocardial infarction range in the four groups of rats,except for the blank group(P<0.05);there were significant differences in the expression levels of IL-1β,IL-18,TNF-α,and ET-1 in the five groups of rats(P<0.05).Conclusion:Catechins can reduce the severity of myocardial injury,reduce the range of myocardial infarction,and reduce myocardial inflammation in rats with coronary heart disease by up-regulating expression level of PI3K/Akt/eNOS signaling pathway-related proteins.Compared with aspirin,high-dose catechins have a more prominent protective effect on the myocardium of rats with coronary heart disease.

Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation

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.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

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.

Melanin nanoparticles alleviate sepsis-induced myocardial injury by suppressing ferroptosis and inflammation

Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a critical role in the development of heart diseases.Therefore,we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury.Herein,we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles(MMPP)improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway.In LPS-induced murine sepsis model,after a single dose intravenously injection of MMPP treatment,MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis.In vitro,MMPP inhibited cardiomyocyte death by attenuating oxidative stress,inflammation and maintaining mitochondrial homeostasis.Collectively,our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation,which might be a novel therapeutic approach in future.