Protección miocárdica

J Integr Med. 2025 Jun 13:S2095-4964(25)00081-0. doi: 10.1016/j.joim.2025.06.002. Online ahead of print.

ABSTRACT

OBJECTIVE: The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.

METHODS: Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA).

RESULTS: Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.

CONCLUSION: Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; Epub ahead of print.

PMID:40562587 | DOI:10.1016/j.joim.2025.06.002

Phytomedicine. 2025 Jun 17;145:156990. doi: 10.1016/j.phymed.2025.156990. Online ahead of print.

ABSTRACT

BACKGROUND: Yangxinshi tablet (YXST), as the traditional Chinese medicine, could significantly improve cardiac function and exercise tolerance in patients with coronary heart disease. However, molecular mechanisms of YXST protecting against myocardial injury and promoting skeletal muscle exercise capacity is still unclear.

PURPOSE: This study aimed to clarify the efficacy and potential mechanisms of YXST in myocardial injury and skeletal muscle exercise capacity.

METHODS: Mice were randomly divided into 6 groups (n = 10-20 every group) and administrated for 6 weeks: control group, myocardial ischemia‒reperfusion group (I/R group), YXST group (I/R mice treated with YXST, respectively 250,500 and 1000 mg/kg/day) and I/R treated with trimetazidine (TMZ) group (20 mg/kg/day). Meanwhile, the mice were divided into 4 groups (n = 8-9 every group), which were control group, YXST group (250, 500 and 1000 mg/kg/day for 6 weeks). Cardiac function, exercise tolerance, grip strength, skeletal muscle structure and myoblasts proliferation were detected. RNA-sequence assays and mass spectrometry analysis of C2C12 myotubes were performed and analyzed. UHPLC was employed to detect YXST's characterize and its principal components. The target protein of YXST were assessed by molecular docking methods. Mitochondria oxygen consumption rate was detected by Seahorse.

RESULTS: YXST improved cardiac function and exercise tolerance, enhanced the slow type I fibers expression, ameliorated mitochondrial biogenesis, and attenuated inflammation level under I/R condition in vivo. YSXT could directly promote exercise capacity and satellite cells proliferation of skeletal muscle under normal condition in vivo. We also found that YXST promoted C2C12 myoblasts differentiation and myotubes formation by regulating mitochondrial biogenesis, mitophagy, and oxidative phosphorylation in vitro. Molecular docking analysis demonstrated that the top 9 compounds identified in blood may bind with BTB and CNC homology 1 protein (BACH1). CETSA assay revealed that YXST had a significantly effect on increasing the thermal stability of BACH1 protein. Interestingly, YXST stimulated the secretion of cardioprotective myokines.

CONCLUSION: This study revealed that YXST improved cardiac function and exercise tolerance in I/R mice, particularly we found that YXST could directly enhance the exercise capacity of mice under normal condition. Mechanismly, YXST significantly regulated mitochondrial biogenesis, oxidative phosphorylation and myokine production in vivo and in vitro. Our findings provide novel mechanistic insights and pharmacological basis for the application of YXST against coronary heart disease and skeletal muscle injury.

PMID:40561862 | DOI:10.1016/j.phymed.2025.156990

Biochem Biophys Res Commun. 2025 Jun 21;776:152242. doi: 10.1016/j.bbrc.2025.152242. Online ahead of print.

ABSTRACT

Despite its potent chemotherapeutic efficacy, cyclophosphamide (CP) is associated with severe cardiac complications, limiting its clinical utility. Recent evidence suggests that the mucolytic agent ambroxol (ABX) exhibits antioxidant and anti-inflammatory properties, making it a candidate for mitigating CP cardiotoxicity. This study explored the protective effects of ABX against CP-mediated cardiotoxicity, with emphasis on oxidative stress, NF-κB/NLRP3 inflamamsome axis and Nrf2/HO-1 signaling. Rats were administered ABX (20 mg/kg) for 7 days and received a single injection of CP (100 mg/kg) on day 5, and blood and heart samples were collected for analyses. CP administration induced significant cardiac dysfunction, marked by elevated LDH, CK-MB, and troponin-I, alongside histopathological evidence of myocardial injury. ABX alleviated cardiac biomarkers, prevented histopathological alterations, reduced lipid peroxidation, and restored antioxidant defenses. CP upregulated NF-κB p65, NLRP3, ASC1, caspase-1, gasdermin D, and IL-1β, and suppressed Nrf2 and HO-1 in the heart of rats. ABX suppressed the NF-κB/NLRP3 inflamamsome axis mediators and upregulated Nrf2 and HO-1. In silico data revealed the binding affinity of ABX towards NF-κB p65 and NLRP3 and ASC1 PYD domains. In conclusion, ABX confers significant protection against CP-induced cardiotoxicity through multifaceted mechanisms, including attenuation of oxidative stress, inhibition of NF-κB/NLRP3 inflamamsome axis, and upregulation of Nrf2/HO-1 signaling. These findings suggest that ABX could serve as an effective adjunct therapy to improve the safety profile of CP in clinical oncology.

PMID:40561755 | DOI:10.1016/j.bbrc.2025.152242

PLoS One. 2025 Jun 25;20(6):e0326249. doi: 10.1371/journal.pone.0326249. eCollection 2025.

ABSTRACT

Low cardiorespiratory fitness (CRF) is a well-established risk factor for cardiovascular disease (CVD) and all-cause mortality. Since CRF is largely genetically determined, understanding the genetic influences on CRF might reveal the protective mechanisms of high CRF. One gene found to be associated with CRF is COX7A2L. COX7A2L is a mitochondrial supercomplex assembly factor, but its role in cellular metabolism remains a topic of discussion. We hypothesized that COX7A2L could play a role in cellular respiration in cardiomyocytes, affecting cardiac function and CRF. To determine the effect of COX7A2L on cardiomyocyte function, we overexpressed and knocked down COX7A2L in human AC16 cardiomyocytes and performed MTT assays and Seahorse XF Cell Mito Stress Tests to assess cell viability and mitochondrial function. For the mitochondrial function measurements, we stimulated the cells with isoproterenol to investigate if the effect of altering COX7A2L levels would be larger under simulated increased energy demand. Overexpression and knockdown were validated using sandwich ELISA. Our findings showed that altering COX7A2L expression in human AC16 cardiomyocytes did not significantly affect cell viability or mitochondrial function. Further research is necessary to determine whether COX7A2L influences cardiomyocyte function and CRF.

PMID:40560843 | PMC:PMC12194157 | DOI:10.1371/journal.pone.0326249

Am J Physiol Cell Physiol. 2025 Jun 25. doi: 10.1152/ajpcell.01006.2024. Online ahead of print.

ABSTRACT

Aberrant autophagy mediated by AMPK/mTOR/ULK1 pathway (a canonical autophagy pathway) plays important roles in diabetic cardiomyopathy (DCM). Asprosin (ASP) secreted by white adipose tissue involves in systemic metabolism disorders. However, its role in DCM remains poorly understood. Therefore, the purpose of this study was to investigate its roles and underlying mechanism in the DCM from the perspective of autophagy and apoptosis. In the in vivo experiments, we observed the effects of ASP-deficiency (ASP-/-) or ASP intervention on cardiac function, fibrosis, autophagy and apoptosis in a diabetes mellitus (DM) mouse model induced by high-fat feeding and streptozotocin (STZ) injection; in the in vitro experiments, we evaluated the effects of ASP intervention with or without 3-MA (autophagy inhibitor) or siAMPK in a H9c2 model injured by high glucose (HG). Our results show that ASP intervention attenuates the myocardial injury induced by DM (P<0.05) and HG (P<0.05). Additionally, the autophagy level markedly increases (P<0.05) in diabetic mice and ASP-deficiency worsens the increase induced by DM (P<0.05). In contrast, ASP intervention alleviates over-autophagy induced by DM (P<0.05) or HG (P<0.05). Mechanistically, the protective effect of ASP against myocardial injury is through inhibiting the over-autophagy mediated by AMPK/mTOR/ULK1 pathway (P<0.05). Taken together, the findings suggest that ASP would be a potential therapeutic target and the recombinant ASP might be a promising candidate to treat metabolism-associated CVD. Although the findings would present a promise for the treatment of DCM, it is worth noting that the mouse model used fails to fully mimic the human DCM pathophysiology.

PMID:40560772 | DOI:10.1152/ajpcell.01006.2024

JACC Asia. 2025 Jun 2:S2772-3747(25)00265-0. doi: 10.1016/j.jacasi.2025.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: Lower socioeconomic status, intelligence, and cognition are linked to a higher likelihood of atrial fibrillation (AF). However, whether these factors directly cause AF or whether others mediate this relationship is unclear.

OBJECTIVES: Our study aimed to determine the causal link between lower socioeconomic status, intelligence, cognition, and AF, and identify mediators.

METHODS: We conducted a 2-sample Mendelian randomization analysis with data from European ancestry genome-wide association studies. Genetic instruments for education, intelligence, cognition, income, and occupation (n = 248,847-1,131,881) evaluated their relationship with AF (FinnGen study: 50,743 cases and 210,652 control subjects; 6 European studies: 60,620 and 970,216).

RESULTS: The pooled results from meta-analysis combining data from 2 studies indicated that education, intelligence, and cognition were causally associated with AF (P < 0.05). Genetically predicted, each 1-SD increase in educational attainment was associated with a 19% decreased risk of AF (OR: 0.81; 95% CI: 0.71-0.92), independent of intelligence and cognition. Among 44 candidate mediators, 8 factors were identified to mediate the education-AF association, including heart failure (mediation proportion: 95.35%), body fat mass (44.05%), waist circumference (42.93%), coronary heart disease (30.1%), body mass index (29.0%), myocardial infarction (28.8%), diastolic blood pressure (21.7%), and waist-to-hip ratio (14.3%).

CONCLUSIONS: Our study suggests that education exerts a causal and protective effect against AF, independent of intelligence and cognition. Heart failure, obesity, and ischemic heart disease serve as mediating factors in the pathway from education to AF, underscoring the importance of considering these conditions in preventing AF associated with education inequality.

PMID:40560110 | DOI:10.1016/j.jacasi.2025.04.008

Adv Sci (Weinh). 2025 Jun 25:e00096. doi: 10.1002/advs.202500096. Online ahead of print.

ABSTRACT

Pulmonary vascular remodeling, which current therapeutic targets fail to alleviate disease severity, plays a key role in pulmonary arterial hypertension (PAH). Irisin is identified as a protective factor involved in regulating inflammation and oxidative stress, but its role in PAH remains unknown. To investigate, plasma irisin levels and its local pulmonary artery expression are measured in patients with PAH and mouse models. Irisin expression is significantly decreased in patients with PAH and PAH mouse models. Furthermore, overexpression and exogenous injection of irisin effectively alleviate hemodynamic and right-heart function in PAH mouse models, meanwhile, it also reverses proliferation and cell cycle progression of pulmonary artery smooth muscle cells (PASMCs). To illustrate the mechanism of irisin exerts on PAH, Enolase 1 is identified as a key irisin-interacting protein. Irisin suppresses proliferation of PDGF-induced PASMCs by promoting ubiquitination status of Enolase 1 via E3 ligase of down regulated protein 4 in neural precursor cell development. Co-immunoprecipitation and molecular docking analyses verifies the interaction and binding sites between irisin and its interactive proteins. Overall, these findings suggest that, irisin is a novel protective factor downregulated in PAH. By ubiquitination, irisin promotes Enolase 1 degradation and suppresses cell proliferation and pulmonary vascular remodeling in PAH.

PMID:40560058 | DOI:10.1002/advs.202500096

J Cardiovasc Dev Dis. 2025 Jun 12;12(6):222. doi: 10.3390/jcdd12060222.

ABSTRACT

Background: Antegrade root cardioplegia remains the most popular strategy for myocardial protection during coronary artery bypass graft (CABG) performed with cardiopulmonary bypass (CPB) and aortic cross clamp. In patients with depressed left ventricular function, however, especially if associated with severe multiple coronary stenosis, increased pharmacological and/or mechanical support in the early post-CPB period is often required to support left ventricular recovery. In this study, we analyzed the results of a myocardial protection strategy that includes selective infusion of cardioplegia through each venous graft followed by warm reperfusion distal to each coronary anastomosis until complete removal of the aortic clamp (total antegrade cardioplegia infusion and warm reperfusion = TAWR) to improve early postoperative recovery in patients with depressed left ventricular function undergoing multi-vessel CABG. Methods: Out of 97 patients undergoing CABG using the TAWR strategy for myocardial protection, 32 patients presented with depressed left ventricle function (EF < 40%) and multi-vessel coronary diseases requiring ≥2 vein grafts and were enrolled as Group A. Combined primary outcomes and postoperative early and late left ventricle recovery (including spontaneous rhythm recovery, inotropic support and postoperative troponin release) were analyzed and compared with those of 32 matched patients operated on using standard antegrade root cardioplegia and limited warm reperfusion through LIMA graft (SAWR) enrolled as Group B. Results: Two patient died in hospital (in-hospital mortality 3.1%) with no statistical differences between the two groups. In Group A 27 patients (90%) had spontaneous recovery of idiopathic rhythm compared to 17 (53%) in group B (p = 0.001). Early inotropic support was required in nine patients (28%) of group A and seventeen patients (53%) of group B (p = 0.041). Furthermore, in eight patients (25%) of group A and seventeen (53%) of group B (p = 0.039) inotropic support was continued for >48 h. Conclusions: The TAWR strategy seems to significantly improve early postoperative cardiac recovery in patients with left ventricle depression undergoing multi-vessel CABG, when compared with SAWR strategy and could therefore be considered the strategy of choice in this subset of patients.

PMID:40558657 | PMC:PMC12193456 | DOI:10.3390/jcdd12060222

Cells. 2025 Jun 18;14(12):924. doi: 10.3390/cells14120924.

ABSTRACT

Muscle loss unresponsive to nutritional supplementation affects up to 80% of cancer patients and severely reduces survival and treatment response. Exercise may help preserve muscle mass and function, yet the translatability of preclinical methods remains questionable. This study aimed to assess how voluntary wheel running, a clinically relevant physical activity, protects skeletal and cardiac muscle against cancer-mediated dysfunction and identify underlying molecular mechanisms.

METHODS: BALB/c mice were assigned to sedentary nontumor-bearing (SED+NT), sedentary tumor-bearing (SED+T), wheel run nontumor-bearing (WR+NT), and wheel run tumor-bearing (WR+T). Tumor-bearing groups received 5 × 105 C26 cells; WR mice had wheel access for 4 weeks. Muscle function and tissue were analyzed for protective mechanisms.

RESULTS: SED+T mice exhibited significant fat and lean mass loss, indicating cachexia, which was prevented in WR+T mice. SED+T also showed 15% reduced grip strength and cardiac dysfunction, while WR+T preserved function. WR+T mice had lower expression of muscle wasting markers (Atrogin1, MuRF1, GDF15, GDF8/11). Physical activity also reduced tumor mass by 57% and volume by 37%.

CONCLUSION: Voluntary wheel running confers tumor-suppressive, myoprotective, and cardioprotective effects. These findings support physical activity as a non-pharmacological strategy to combat cancer-related muscle wasting and dysfunction.

PMID:40558549 | PMC:PMC12190267 | DOI:10.3390/cells14120924

J Cardiovasc Transl Res. 2025 Jun 24. doi: 10.1007/s12265-025-10647-6. Online ahead of print.

ABSTRACT

The acute pathophysiological changes after myocardial ischemia complicated by cardiogenic shock (CS) remain poorly defined, especially regarding compensatory mechanisms and myocardial mitochondrial function. We investigated immediate cardiovascular and mitochondrial effects in a porcine model of ischemic CS. CS was induced in 32 Danish Landrace pigs (60 kg) via repeated microembolization of the left coronary artery until a 30% reduction in cardiac output (CO) or mixed venous saturation. Monitoring included pulmonary artery and left ventricular pressure-volume catheters, with analysis of endomyocardial biopsies and arterial, mixed venous, and coronary sinus blood samples. CO deteriorated promptly due to decreased stroke volume. Contractility declined, and afterload increased, causing rapid ventriculo-arterial decoupling. Forward flow parameters were compromised prior to pressure-parameters. Diastolic function was impaired and mitochondrial damage was observed. CS rapidly impairs LV hemodynamic and mitochondrial function, highlighting the importance of monitoring forward flow and targeting mitochondrial function in treatment.

PMID:40555857 | DOI:10.1007/s12265-025-10647-6

Ann Vasc Surg. 2025 Jun 17:S0890-5096(25)00424-8. doi: 10.1016/j.avsg.2025.05.054. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to create a risk score for the development of perioperative myocardial infarction (MI) following carotid endarterectomy (CEA) utilizing weighted variables from the Vascular Qualitative Initiative (VQI) database, which have a multivariable significant association with the event.

METHODS: The VQI CEA module was queried between January 2003 and October 2023 and 192,547 procedures met the study inclusion criteria. Both symptomatic and asymptomatic patients were included. An internal VQI validation cohort was similarly created with the same exclusion criteria utilizing CEA performed between November 2023 and October 2024, over which time period 17,449 individuals met the inclusion criteria. The primary study outcome was perioperative MI at CEA. Univariable analysis was conducted followed by binary logistic regression analysis utilizing significant univariable factors. Regression beta-coefficient was used to create a weighted risk score for MI and internal validation with testing at each risk score was conducted. Mortality rates in long-term follow up for those with vs. without MI was investigated.

RESULTS: MI occurred in 0.7% of cases (N=1299). The following factors had a significant (P<.05) multivariable association with perioperative MI for CEA : female sex; advancing age; rural home status; diabetes; history (Hx) of coronary artery disease (CAD); MI or angina pectoris within 6 months of surgery; coronary artery bypass grafting (CABG) >5 years ago; congestive heart failure regardless of severity; renal insufficiency; positive stress test within two years; anemia; Hx of peripheral arterial disease intervention; prior CEA or carotid artery stenting; dual antiplatelet therapy at time of presentation; modified Rankin score ≥2 at time of CEA; and urgent/emergent CEA. Not having had a Hx of prior MI in combination with having no current CAD symptom was protective (P<.001) for perioperative MI. There was significant escalation noted with increasing risk score as patients with scores of ≤5 experienced MI in just 0.2% of cases whereas patients with risk scores of >25 experienced MI at a >20 times higher rate of 4.1%. AUC analysis for the risk score had a value of 0.70. Application of the risk score to the validation cohort resulted in a similar AUC value of 0.72.

CONCLUSIONS: A risk score for the event of perioperative MI at the time of CEA has been developed that has good accuracy. Patients experiencing perioperative MI have a significantly increased 5-year mortality rate relative to those without. Given the significant impact of perioperative MI on long-term survival, this risk score has important implications for perioperative cardiac risk assessment and optimization strategies.

PMID:40553834 | DOI:10.1016/j.avsg.2025.05.054

Cardiovasc Hematol Disord Drug Targets. 2025 Jun 19. doi: 10.2174/011871529X367923250609171115. Online ahead of print.

ABSTRACT

INTRODUCTION: Oroxylin A is primarily sourced from the roots of Scutellaria baicalensis, a medicinal plant commonly used in traditional Chinese medicine. It can also be found in other Scutellaria species. The plant's rich bioactive profile makes it a significant source of various flavonoids, including Oroxylin A.

AIM: The proposed aim of this study is to investigate in-vitro anti-oxidant activity, toxicity studies and in-vitro cardioprotective activity of Oroxylin-A against Doxorubicin mediated myocardial damage on H9c2.

METHODS: The total phenolic content was estimated using Folin-Ciocalteu test and in-vitro activity was performed using DPPH assay. Acute toxicity studies were performed according to OECD 423 guidelines. In vitro cardioprotective activity was performed on H9c2 cells and was estimated for the biomarkers.

RESULTS: Oroxylin-A showed good antioxidant activity. No abnormalities were found in animals upon its usage, indicating that Oroxylin-A was safe at 2000 mg/kg. 150ug/ml of Oroxylin-A significantly increased the cell viability up to 99% and also decreased the LDH and ROS generation indicating that Oroxylin-A showed significant cardioprotective activity on H9c2 cells.

CONCLUSION: This research underscores the potential of Oroxylin A as a candidate for further investigation as a cardioprotective agent. Also, the present study contributes to the growing body of knowledge aimed at identifying natural compounds that may offer protective effects against myocardial damage, providing hope for future therapeutic interventions in the field of cardiovascular medicine.

PMID:40551683 | DOI:10.2174/011871529X367923250609171115

J Biochem Mol Toxicol. 2025 Jul;39(7):e70365. doi: 10.1002/jbt.70365.

ABSTRACT

This systematic review and meta-analysis were conducted to evaluate the therapeutic efficacy of Astragaloside IV (As-IV) in ischemic heart disease based on the preclinical evidence and to correlate the cardioprotective effect with various available mechanisms. This systematic review and meta-analysis were conducted based on the results of a thorough literature search in databases of published papers, such as PubMed, Embase, and Google Scholar. A total of 18 studies that met the inclusion/exclusion criteria were included. The meta-analysis has shown the significant therapeutic efficacy of As-IV on ischemic heart disease. As-IV has decreased the myocardial infarction size, the left ventricular weight indices, the left ventricular internal diameter in systole, and the left ventricular internal diameter in diastole. As-IV has decreased the level of the third type of collagen and the decreased activity of creatine kinase and lactate dehydrogenase. Also, As-IV has markedly decreased the rate of apoptosis and the expression of the proapoptotic markers such as caspase-3 and Bax. The left ventricular systolic pressure, as well as the arterial shortening edge and the ejection fraction, has increased. The levels of the antiapoptotic protein Bcl-2 increased. In addition, As-IV has a powerful anti-inflammatory influence by inhibiting the main markers of inflammation, such as TLR4, IL-1, TNF-α, and TGF-β. As-IV has also caused an effect on angiogenesis by increasing the VEGF level. The results have revealed the As-IV, as a decent universal medicine for ischemic heart disease because of its variety of actions and effectiveness.

PMID:40551496 | PMC:PMC12186012 | DOI:10.1002/jbt.70365

J Med Food. 2025 Jun 24. doi: 10.1089/jmf.2025.k.0031. Online ahead of print.

ABSTRACT

Doxorubicin (DOX), an anthracycline-based anticancer drug, is commonly used to treat various cancers, but its prolonged use may lead to cardiotoxicity. Despite extensive research efforts, effective strategies for managing DOX-induced cardiotoxicity (DICT) remain limited. This study investigated the DICT-inhibitory efficacy of the water extract of Allium victorialis L. (AVE) and its underlying mechanism. AVE protected mouse cardiomyocytes, H9c2 cells, from DOX-induced toxicity while not interfering with DOX's cytotoxic effect on the MDA-MB-231 cells, human breast cancer cells. DOX-induced abnormal heart rate, RR interval, cQT prolongation, and segmentation were normalized following AVE supplementation. Also, AVE reduced the serum levels of creatine kinase and lactate dehydrogenase and suppressed myocardial fibrosis and cell death by DICT in the AVE-fed mice group. Moreover, AVE was shown to restore DOX-induced impaired electrophysiological changes in human-induced pluripotent stem cell-derived cardiomyocytes, including reduced total activity and decreased conduction velocity, while also normalizing the beat period irregularity and beat period mean. A total of 57 metabolites were tentatively identified in the AVE sample. Furthermore, PCR microarray and western blot analyses confirmed that AVE reversibly increased the expression of antioxidant-related genes and proteins. Altogether, the antioxidant properties of AVE could be utilized as a new strategy for preventing and treating DICT.

PMID:40551413 | DOI:10.1089/jmf.2025.k.0031

Cardiovasc Diabetol. 2025 Jun 23;24(1):260. doi: 10.1186/s12933-025-02822-5.

NO ABSTRACT

PMID:40551100 | PMC:PMC12183802 | DOI:10.1186/s12933-025-02822-5

Anal Bioanal Chem. 2025 Jun 23. doi: 10.1007/s00216-025-05969-y. Online ahead of print.

ABSTRACT

Diabetic cardiomyopathy (DCM), a cardiac complication of diabetes, is characterized by diastolic dysfunction, myocardial fibrosis, and structural remodeling. Carbonyl-containing metabolites (CCMs) play a critical role in driving DCM pathogenesis through metabolic dysfunction, oxidative stress, and lipid peroxidation. In this study, we employed an on-tissue chemical derivatization (OTCD)-based air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) approach to investigate spatial metabolic alterations of CCMs in the diabetic rat heart. This method enabled the spatial profiling of 369 CCMs-including 137 fatty aldehydes (FALs), 214 oxo fatty acids (OFAs), and 18 sterol-type lipids (STs)-across cardiac tissue sections. This expanded metabolite coverage revealed marked spatial heterogeneity in cardiac metabolism. Comparative analysis between diabetic and control rats identified 162 significantly altered CCMs, highlighting localized metabolic dysregulation associated with DCM. To explore potential therapeutic interventions, we further evaluated the metabolic impact of ferulic acid, a candidate agent for myocardial protection. High-dose ferulic acid treatment significantly modulated 43 differential CCMs, attenuated pyruvate accumulation, restored fatty aldehyde levels, and improved the profile of oxidized fatty acids. These findings suggest that ferulic acid ameliorates metabolic dysfunction by exerting antioxidant and anti-inflammatory effects, while enhancing mitochondrial function and lipid metabolism. Overall, this study demonstrates the utility of OTCD-AFADESI-MSI for spatially resolved metabolomic analysis of carbonyl stress in DCM and supports the therapeutic potential of ferulic acid in managing diabetic heart injury.

PMID:40551014 | DOI:10.1007/s00216-025-05969-y

BMJ Open. 2025 Jun 23;15(6):e096433. doi: 10.1136/bmjopen-2024-096433.

ABSTRACT

INTRODUCTION: Total hip arthroplasty (THA) is an effective treatment for severe osteoarthritis. However, THA has a high surgical risk for patients with concomitant diseases and is associated with several serious complications, such as myocardial infarction, acute kidney injury and cognitive dysfunction. This study will explore the potential protective effects of remote ischaemic preconditioning (RIPC) in cemented THA patients.

METHODS AND ANALYSIS: The PRINCIPAL study is designed as a randomised, controlled, parallel-group, blinded trial to assess the impact of RIPC in cemented THA patients. The study will compare two patient groups-one group will have the RIPC procedure, and the second will have the sham procedure. The primary outcome is the peak troponin T concentration during the three postoperative days. Secondary outcomes include markers of arterial stiffness (augmentation index (AIx), carotid-femoral pulse wave velocity, central blood pressures), neural (neuron-specific enolase, S100B) and renal injury biomarkers (estimated glomerular filtration rate, creatinine, cystatin C), markers of systemic inflammation (hypoxia-inducible factor 1-alpha, interleukin (IL)-6, IL-1β, tumour necrosis factor-alpha, IL-10) and oxidative stress (total peroxide concentration, total antioxidant capacity), as well as clinical outcome measures such as major adverse cardiovascular events and all-cause mortality.

ETHICS AND DISSEMINATION: The ethical board of the University of Tartu has granted approval for the study (no. 384T-26). The results of this study will be disseminated in international peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT06323018.

PMID:40550717 | PMC:PMC12186052 | DOI:10.1136/bmjopen-2024-096433

Circulation. 2025 Jun 24;151(25):e1093-e1094. doi: 10.1161/CIRCULATIONAHA.125.074590. Epub 2025 Jun 23.

NO ABSTRACT

PMID:40549847 | DOI:10.1161/CIRCULATIONAHA.125.074590

Circulation. 2025 Jun 24;151(25):e1091-e1092. doi: 10.1161/CIRCULATIONAHA.124.072438. Epub 2025 Jun 23.

NO ABSTRACT

PMID:40549843 | DOI:10.1161/CIRCULATIONAHA.124.072438

World J Diabetes. 2025 Jun 15;16(6):103685. doi: 10.4239/wjd.v16.i6.103685.

ABSTRACT

BACKGROUND: Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.

AIM: To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.

METHODS: High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice. Mice were divided into different groups including control, model, and treatment with various doses of erianin (10, 20, and 40 mg/kg) as well as ML-385 + erianin group.

RESULTS: Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) pathway. Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls. Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function (left ventricular ejection fraction, left ventricular fractional shortening) and mitigated ventricular remodeling (left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole; P < 0.05 vs model group). No significant differences were observed between the ML-385 + erianin and placebo-treated groups. Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation, structural disorganization, inflammatory cell infiltration, and cytolytic damage. Furthermore, it significantly reduced the serum levels of cardiac troponin I, creatine kinase, and its MB isoenzyme. However, the ML-385 + erianin co-treatment failed to alleviate myocardial injury. Metabolic profiling revealed erianin-mediated improvements in glycemic regulation (glycated hemoglobin: P < 0.001), plasma insulin homeostasis, and lipid metabolism (total cholesterol, triglycerides, low-density lipoprotein cholesterol reduction, and high-density lipoprotein cholesterol restoration; P < 0.05 vs model group). Proinflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group, whereas no significant differences were detected between the model and ML-385 + erianin groups. Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups, with the most pronounced effects in the erianin-H group (P < 0.05). Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups. These protective effects were abolished in the ML-385 + erianin co-treatment group, which showed no statistical differences from the model group.

CONCLUSION: Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.

PMID:40548264 | PMC:PMC12179885 | DOI:10.4239/wjd.v16.i6.103685