Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a leading causes of premature death, yet treatment options remain limited. In this study, we developed the easily accessible engineered exosomes for treatment of DMD-associated cardiomyopathy and explored the underlying mechanisms in DmdΔ4 mice, a model harboring hot spot mutation in the dystrophin gene.

DmdΔ4 mice and their cardiomyopathy phenotype were confirmed by Sanger sequencing, pathological staining, flow cytometry, immunoblotting, single-cell sequencing and echocardiographic analysis. Engineered exosomes, exosomes- cardiac homing peptide (Exo-CHP), were synthesised and characterised by click chemistry and miRNA sequence, separately. The targeted ability and the therapeutic effects of Exo-CHP were studied in vitro and in vivo. Primary cardiomyocytes were used to study the underlying mechanism of Exo-CHP.

DmdΔ4 mice showed an obvious cardiomyopathy-associated phenotype. Exo-CHP can target myocardium and mitigate pathological progression of cardiomyopathy in DmdΔ4 mice. The therapeutic effects of intravenously delivered Exo-CHP significantly reduced myocardial inflammation, fibrosis and improved the mice's cardiac function. The rescue effects were mediated through the regulation of gene expression at the transcriptomic level, prevention of dystrophin protein complex degradation, and inhibition of intracellular calcium influx and calpain protease activity. The miR-21 knockdown Exo-CHP can counteract the protective effects of Exo-CHP on the calcium content and membrane integrity of primary DmdΔ4-derived cardiomyocytes.

Our study demonstrated the feasibility, efficacy and the possible mechanism of mesenchymal stromal cell-derived engineered exosomes, positioning them as a potential cell-free intervention for DMD-associated cardiomyopathy.

Cardiac arrhythmias remain a leading cause of cardiovascular morbidity and mortality worldwide. Although conventional antiarrhythmic drugs are effective, their use is constrained by proarrhythmic risks and extracardiac toxicity. Wenxin Keli (WXKL), a traditional Chinese medicine (TCM) formula, has demonstrated antiarrhythmic properties in preclinical and clinical studies with a reportedly favorable safety profile. This article provides a critical synthesis of WXKL's pharmacological mechanisms, including ion channel modulation (INa, ICaL, Ito), calcium handling, and calcium/calmodulin-dependent protein kinase II signaling, with explicit appraisal of translational limitations. Clinical trial evidence and meta-analyses for atrial fibrillation (AF), premature ventricular contractions, and other indications were systematically evaluated, with detailed discussion of effect sizes, heterogeneity, and methodological quality. Key challenges unique to WXKL as a TCM-derived product-formulation variability, quality control limitations, and regulatory approval pathways-are analyzed in depth. A prioritized research agenda is proposed to address evidence gaps. *These authors contributed equally to this work and share first authorship.

Hypertension remains the leading global contributor to cardiovascular mortality. Although renal denervation (RDN) has demonstrated efficacy, the central neurobiological mechanisms sustaining its sympathoinhibitory effects remain unclear. We investigated whether RDN modulates the ATP and P2X7R (P2X7 receptor)/PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) signaling axis in the hypothalamic paraventricular nucleus to attenuate neuroinflammation and blood pressure.

Eight-week-old male spontaneously hypertensive rats were randomly assigned to either sham surgery or RDN (combined physical/chemical ablation; n=8 per group). Systolic blood pressure was longitudinally monitored using tail-cuff plethysmography. Cardiac target-organ injury was assessed using hematoxylin-eosin and Masson's trichrome staining. ATP levels, P2X7R expression, and PI3K/Akt phosphorylation in the paraventricular nucleus were quantified by ELISA, Western blotting, and immunofluorescence. A selective P2X7R antagonist (HY-50697/A-740003) was used for pharmacological validation.

RDN significantly reduced systolic blood pressure in spontaneously hypertensive rats (from 210.3 to 143.2 mm Hg, P<0.0001) and markedly ameliorated left ventricular hypertrophy and myocardial fibrosis. Mechanistically, RDN substantially decreased ATP concentrations in the paraventricular nucleus (from 406.81 to 292.98 nmol/L, P<0.0001), downregulated P2X7R protein expression, and suppressed pathological activation of the PI3K/Akt signaling pathway, accompanied by reduced proinflammatory cytokine production. Pharmacological inhibition of P2X7R functionally phenocopied the antihypertensive and central anti-inflammatory effects induced by RDN.

RDN was associated with reduced blood pressure and attenuation of central ATP-related neuroinflammatory signaling, beyond peripheral sympathetic disruption. The ATP/P2X7R/PI3K/Akt axis may represent a candidate pathway linking renal signaling to central sympathetic regulation, warranting further investigation as a potential mechanistic target in resistant hypertension.

BACKGROUND Congenital absence of the right coronary artery (RCA) is a rare anomaly often identified incidentally. We report a case of transient left ventricular systolic dysfunction followed by recovery of ejection fraction and new-onset mitral chordal rupture, which became the primary driver of pronounced N-terminal pro-B-type natriuretic peptide (NT-proBNP) elevation. The coexistence of 2 distinct pathologies complicated causal attribution; we discuss proposed mechanisms while recognizing their limitations. CASE REPORT A 58-year-old woman presented with exertional chest pain. At initial admission, she exhibited sinus tachycardia, elevated NT-proBNP (910 pg/mL), and reduced left ventricular ejection fraction (LVEF; 43% [M-mode]) with hypokinesis of the anterior wall and anteroseptum. Symptoms improved with anti-ischemic therapy. Three weeks later, LVEF recovered to 56% (biplane Simpson method), but NT-proBNP increased to 2440 pg/mL. Echocardiography revealed rupture of a small chord of the anterior mitral leaflet with mild-to-moderate regurgitation and elevated filling pressures (E/e'=13.8). Coronary angiography demonstrated congenital absence of the RCA ostium, with an enlarged left circumflex artery supplying the RCA territory and no evidence of atherosclerotic stenosis. Retrospective quantitative mitral regurgitation indices from archived images were examined. Management was conservative; symptoms resolved and NT-proBNP levels decreased during follow-up. CONCLUSIONS In patients with rare coronary anomalies, newly acquired common valvular disease may dominate the clinical presentation. Transient systolic dysfunction and subsequent chordal rupture occurred in our patient; a direct causal relationship remains speculative. Multimodality imaging is essential to accurately attribute hemodynamic changes and guide therapy. Long-term surveillance of coronary anatomy and valve function is recommended.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for a substantial proportion of global deaths. Increasing evidence indicates that cardiovascular susceptibility is shaped during fetal development, where the intrauterine environment plays a critical role. Maternal-fetal crosstalk, mediated largely through placental function, coordinates the transfer of metabolic, endocrine, and immune signals that are essential for normal cardiac and vascular development. Disruptions in maternal physiology-including metabolic disorders, hypertensive conditions, inflammation, and environmental stress-can perturb this communication network and alter the intrauterine milieu. These changes induce persistent modifications in cardiomyocyte growth, endothelial function, and key regulatory pathways, thereby contributing to long-term cardiovascular risk. Emerging studies highlight that cardiovascular programming is governed by interconnected mechanisms involving epigenetic regulation, mitochondrial function, immune signaling, and intercellular communication. This review synthesizes current evidence on how maternal-fetal crosstalk shapes cardiovascular development beyond genetic determinants and provides an integrated framework linking early-life exposures to lifelong cardiovascular health.

Ferroptosis is a regulated form of cell death in which disturbed iron metabolism, accumulation of peroxidized membrane lipids, and insufficient glutathione peroxidase 4 (GPX4) activity converge to injure vascular cells. In atherosclerosis, its effects are highly dependent on cellular context rather than being uniform across the vessel wall. In macrophages, ferroptotic injury strengthens inflammatory signaling and contributes to necrotic-core growth; in vascular smooth muscle cells, it impairs mitochondrial fitness, contractile phenotype maintenance, and extracellular matrix support, thereby weakening the fibrous cap; and in endothelial cells, it disrupts redox homeostasis and barrier function, facilitating lipid entry and early lesion formation. This review synthesizes recent advances in the molecular regulation of ferroptosis in atherosclerosis and emphasizes how its functional consequences differ among plaque-resident cell types. We also discuss natural products and traditional Chinese medicine-derived compounds as promising modulators of ferroptosis-related pathways, owing to their multi-target actions and potential suitability for chronic vascular intervention. By connecting mechanistic evidence with therapeutic implications, we propose that cell-type-aware regulation of ferroptosis, rather than indiscriminate suppression, may offer a rational strategy for plaque stabilization and cardiovascular risk reduction. Significance: Ferroptosis is increasingly recognized as an important contributor to atherosclerosis, but its vascular effects vary substantially among endothelial cells, macrophages, and vascular smooth muscle cells. This review analyzes how cell-specific differences in iron handling, lipid peroxidation, and antioxidant defenses shape plaque initiation, inflammatory progression, and fibrous-cap stability. We further summarize evidence that natural compounds can modulate these ferroptosis-related networks and restore redox and cellular homeostasis. By linking vascular cell heterogeneity with natural product-based intervention strategies, this review provides a mechanistic and translational framework for more precise targeting of ferroptosis in atherosclerosis.

Financial strain is associated with suicide risk; however, no research has examined financial stressors in the year preceding suicide using national credit data.

To assess financial stressors in the 12 months preceding suicide in a national sample of veterans by linking financial, mortality, and health care records.

This case-control study of 5000 veterans who died by suicide (January 1, 2015 to December 31, 2017) used mortality data from the US Department of Veterans Affairs (VA) and the US Department of Defense. Cases were matched to 12 500 living controls on age, sex, VA health care use, and suicide index date. Analyses were conducted in December 2025.

Financial stressors in the prior 12 months were identified in TransUnion credit records provided by FinThrive.

The primary outcome was death by suicide. Differences between cases and controls were analyzed using multivariable conditional logistic regression, adjusting for demographics and, among VA users, marital status and diagnoses of depression, posttraumatic stress disorder, and substance use disorder.

Among 17 439 veterans included in this study, the mean (SD) age was 52.9 (15.7) years, and 94.6% were male. Suicide was associated with having (vs not having) delinquent mortgage payments (odds ratio [OR], 1.4; 95% CI, 1.2-1.7), repossessions (OR, 1.9; 95% CI, 1.3-2.7), and credit card payments 30 or more days past due (OR, 1.7; 95% CI, 1.6-1.9). Lower credit score categories were associated with increasing odds of suicide. Veterans with 3 or more financial stressors had higher odds of suicide (OR, 2.4; 95% CI, 1.9-3.0) compared with those who had none. Among individuals with available data, credit score declines of 51 to 100 points (OR, 1.3; 95% CI, 1.1-1.5) and greater than 100 points (OR, 2.8; 95% CI, 2.3-3.5) over 1 year, relative to no change in score, were associated with increased odds of suicide. Cumulative financial stressors and declining credit scores had the highest ORs for suicide when adjusting for demographics and, among VA users, marital status and prior psychiatric diagnoses. ORs were lower among VA users than among non-VA users.

In this case-control study, suicide was associated with financial stressors in the prior 12 months. Incorporating financial stressors into clinical evaluations and safety planning may aid in identifying patients at risk for suicide. Policymakers and researchers could consider strategies to detect and mitigate financial stressors as part of comprehensive suicide prevention efforts.

Sexual and gender minoritized adolescents (SGMA) are at higher risk for self-injurious thoughts and behaviors (STB), such as suicide and nonsuicidal self-injury, compared to their heterosexual and cisgender peers. This study explored treatment experiences, barriers, and facilitators to treatment for SGMA at risk for STB. Participants were 18 SGMA, aged 13-19 years (M = 16.8; SD = 1.89); 61% were transgender or nonbinary; 61% plurisexual; and 78% White, non-Hispanic/Latine. Participants completed a semistructured interview, including questions about their experiences seeking mental health treatment for STB. Several themes emerged for negative treatment experiences (e.g., overemphasis on identity, invalidation), positive treatment experiences (e.g., affirmative work), barriers to treatment (e.g., shame, structural barriers), facilitators to treatment (e.g., family support), and recommendations to mental health professionals. The findings of this study provide insights into the varied STB treatment experiences of SGMA at risk for STB. These results underscore the importance of SGM-affirmative clinical practice and have significant implications for research and clinical interventions for SGMA. Additionally, our findings provide useful recommendations from SGMA to help guide mental health professionals in developing SGM-affirmative interventions. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Health care staff work in high-stress environments that increase risk for mental health challenges; however, racial/ethnic minority staff may be less likely to access care. Understanding mental health service utilization patterns and barriers among diverse health care staff is essential for developing culturally responsive interventions. An anonymous cross-sectional survey was distributed to health care staff at a large urban hospital (September to October 2022). The survey assessed demographics, occupational stressors, mental health symptoms, service utilization, and perceived barriers to care. Descriptive and bivariate analyses examined differences by race/ethnicity, and multinomial logistic regression identified correlates of perceived need and service utilization. Of 4,998 invited staff, survey responses were available for 1,119 (22.4%) participants, and 811 were included in regression analyses. Participants identified as White (28.2%), Asian (24.2%), Hispanic (24.8%), and Black (22.8%); most were women (84%) and ages 20-39 (52.3%). Asian, Black, and Hispanic staff were more likely to report no perceived need for mental health services compared with White staff. Service utilization was highest among White participants (26.4%) and lowest among Asian participants (14.9%). Across all racial and ethnic groups, the most frequently endorsed barriers were related to behavioral intention to seek services, knowledge, and inconvenient timing. Racial and ethnic minority health care staff reported lower mental health service utilization despite similar workplace stressors. The lower perceived need among minority staff suggests that access-focused interventions alone may be insufficient. Efforts to improve equity should address both access barriers and factors influencing perceived need. (PsycInfo Database Record (c) 2026 APA, all rights reserved).