Thoracic aortic dissection (TAD) is a life-threatening aortic disease without effective medical treatment. Disruption of vascular smooth muscle cell (VSMC) homeostasis plays a vital role in triggering TAD. ELA (ELABELA) is a novel endogenous ligand for APJ (angiotensin receptor AT1-related receptor protein). However, the effects of ELA on TAD formation and development remain elusive.

Four-week-old C57BL/6J male mice were treated with β-aminopropionitrile monofumarate or β-aminopropionitrile monofumarate combined with Ang II (angiotensin II) to induce TAD models, and the aortic rupture occurred mainly in the descending thoracic region. ELA or saline was infused via osmotic minipumps into mice for 4 weeks. Transcriptomic studies and VSMC-derived conditioned medium were used to investigate the downstream molecular mechanisms of ELA.

ELA infusion mitigated TAD development and prevented aortic media degradation in mice, which was reversed by APJ antagonist ML221. Exogenous ELA prevented the disruption of VSMC homeostasis under PDGF (platelet-derived growth factor) stimulation in VSMCs. Based on transcriptomic studies, we showed that ELA significantly inhibits NLRP3 (NLR family pyrin domain-containing 3)/IL (interleukin)-1β pathway activation and modulates NET (neutrophil extracellular trap) formation in vivo and in vitro. In human neutrophils, ELA significantly inhibited NETs' formation, which is prevented by reactive oxidative species supplementation. Using VSMC-derived conditioned medium, we showed that NLRP3/IL-1β-related NETs' formation connects cellular signaling from VSMCs to neutrophils, leading to disruption of VSMC homeostasis. Notably, ELA was downregulated in both plasma and aortic tissues of human TAD, and lower plasma ELA levels were associated with an increased risk of TAD.

We provide evidence that ELA prevents TAD progression and aortic medial degeneration, primarily by maintaining VSMC homeostasis, which may be linked to the inhibition of NETosis in neutrophils and NLRP3/IL-1β-related cellular signaling between VSMCs and neutrophils. ELA shows promise as a target for pharmacological therapy and diagnostic TAD management.

In recent years, the global prevalence of overweight and obesity has exhibited a sustained upward trajectory. As an independent entity within the spectrum of chronic diseases, obesity serves as a significant pathogenic factor for multiple chronic conditions and ranks as the sixth leading risk factor for mortality and disability nationwide. It poses a severe threat to public health while imposing a considerable socioeconomic burden. The etiology of obesity is multifactorial; however, primary diagnostic modalities and therapeutic approaches remain relatively undiversified, and long-term weight maintenance remains challenging. Similar to other chronic diseases, obesity management demands a long-term multimodal strategy. This strategy must incorporate individualized treatment goals and balance the benefits and risks of different interventions to formulate personalized management plans. These plans aim to reduce body weight through multifaceted interventions, alleviate obesity-related comorbidities, enhance quality of life, and optimize overall health outcomes.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Research indicates that inflammatory responses and oxidative stress mediated by reactive oxygen species (ROS) are hallmark pathological mechanisms of CVD. Traditional anti-inflammatory drugs, though widely used, have limitations such as lack of targeting, low systemic delivery efficiency, and significant side effects. Nanozymes are a class of nanomaterials with enzyme-like activity, and their breakthrough applications offer new directions for the prevention and treatment of CVD. In the treatment of cardiovascular diseases, nanozymes demonstrate unique advantages: they can achieve local targeted delivery and ROS scavenging, and can also regulate the inflammatory microenvironment through multi-mechanism interventions. However, despite their promising applications, nanozymes still face challenges such as optimizing catalytic selectivity, improving biological targeting efficiency, and verifying long-term safety. This article will review the mechanisms of action of nanozymes in inflammation regulation and summarize their applications in cardiovascular diseases.

Hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloids (PAs) is a life-threatening liver injury for which standardized chronic models are lacking. This study aimed to establish a clinically relevant chronic PA-HSOS murine model and to identify potential therapeutic targets.

A 28-day model was developed using key alkaloids from Gynura segetum (seneciphylline, senecionine, and N-oxide derivatives), mirroring human exposure. Disease characteristics were evaluated via hematological profiling, CT imaging, histopathology, and transcriptomics. A hepatocyte-liver sinusoidal endothelial cell (LSEC) co-culture system was used to validate molecular mechanisms. TM5441, a Serpine1 inhibitor, was evaluated for therapeutic efficacy.

The model faithfully recapitulated human HSOS, characterized by elevated liver enzymes (ALT, 1.6-fold, p <0.001; AST, 5.7-fold, p <0.0001, n = 6), coagulation dysfunction (prothrombin time, 1.5-fold, p <0.001; activated partial thromboplastin time, 1.1-fold, p <0.05; D-dimer, 8.4-fold, p <0.0001, n = 6), increased liver weight (1.2-fold, p <0.0001, n = 6), reduced VE-cadherin expression (0.28-fold, p <0.001, n = 6), and sinusoidal fibrosis. RNA sequencing identified Serpine1 as the most significantly upregulated gene (|log₂fold-change| ≥2, p <0.05) associated with p53 signaling. Serum Serpine1 was elevated in patients (5.0-fold, p <0.01, n = 16,) and mice (3.7-fold, p <0.001, n = 6) with PA-HSOS. Co-culture confirmed that Serpine1-driven p53 activation (1.8-fold, p <0.01, n = 3) promoted endothelial senescence. TM5441 reduced Serpine1-p53 activity (0.5-fold, p <0.001, n = 6), improved liver function (ALT and AST reduced 30-40%, p <0.001, n = 6), normalized coagulation, restored LSEC integrity (VE-cadherin, 3.2-fold, p <0.001, n = 6), and attenuated inflammation and fibrosis.

This first chronic PA-HSOS murine model closely mirrors human disease and identifies Serpine1 as a critical therapeutic target. Targeting the Serpine1-p53 axis with TM5441 represents a promising strategy to mitigate endothelial injury in PA-HSOS.

This study establishes a chronic PA-HSOS (pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome) model that more accurately replicates human disease progression, thereby overcoming the limitations of previous acute models for mechanistic and therapeutic research. The researchers identify Serpine1 as a key regulatory target that could lead to new therapies for PA-HSOS by reducing endothelial senescence and inflammation. These findings provide clinicians and researchers with improved tools for studying drug-induced liver injury and a pathway for translating discoveries into clinical trials. The therapeutic compound TM5441 shows promise for reversing liver dysfunction and vascular damage, while the model itself may aid in the development of better diagnostic criteria and prevention strategies.

Not applicable.

Vagus nerve stimulation (VNS) is currently approved for conditions such as drug-resistant epilepsy and stroke with promising results. In addition, it is also being investigated for many other conditions. The goal of this study is to review the scope of VNS clinical trials.

We conducted a retrospective review of active and completed clinical trials using ClinicalTrials.gov, with "Vagus Nerve Stimulation" as the search term. The number of studies taking place over time was assessed using Pearson correlation coefficient.

An examination of ClinicalTrials.gov revealed 440 clinical trials, with 346 meeting our inclusion criteria. The number of VNS clinical trials increased annually from 2000 to 2024, demonstrating exponential growth after 2015 (P < 0.001, R² = 0.924). Of these, 42.5% were completed, with published results being available for 9.8% of the completed trials. Completed trials were predominantly from the United States, spanning various conditions including a wide variety of disorders such as cardiovascular diseases (n = 38), chronic pain disorders (n = 31), gastrointestinal disorders (n = 24), autoimmune disorders (n = 23), neurodegenerative diseases (n = 19), COVID-19 (n = 13) and diabetes (n = 11). Among the included trials, 86% were non-invasive with 91% of trials with results reporting improvements in symptoms.

This increasing number of trials assessing a wide breadth of clinical disorders suggests the promising future of VNS as from the currently approved treatments. Physicians should familiarize themselves with these results and potentially upcoming indications for VNS.

Atherosclerotic cardiovascular and cerebrovascular diseases are still the main cause of global incidence rate and mortality. The LDL-C/HDL-C ratio (LHR) has been identified as a potential biomarker for cardiovascular risk. However, the relationship between it and the long-term risk of carotid plaques is not yet clear, especially in low-income populations in China.

This prospective cohort study included adults aged ≥45 years without carotid plaque at baseline from low-income rural areas of Tianjin, China. Baseline characteristics were collected in 2014, and follow-up data were obtained in 2019. The primary outcome was the development of new carotid plaques, assessed using carotid ultrasound. The relationship between the LDL-C/HDL-C ratio (LHR) and new carotid plaques was analyzed using multifactorial logistic regression, with the presence or absence of new-onset plaques as the dependent variable. Additionally, we utilized restricted cubic spline (RCS) regression to visually present the potential nonlinear relationship between LHR and the risk of carotid plaque.

Over the six-year follow-up period, 606 participants (38.3%) developed new carotid plaques. Higher LHR was significantly associated with an increased risk of new carotid plaques, with each unit increase in LHR corresponding to a 35.9% higher risk (OR = 1.359, 95% CI: 1.180-1.566, p < 0.001). The RCS curve indicated a non-linear positive association between LHR and the likelihood of carotid plaques (p for non-linearity = 0.019), with an optimal cut-off at 1.257. Logistic regression analysis confirmed that LHR > 1.257 was linked to increased odds of carotid plaques in both unadjusted (OR: 1.80, p < 0.001) and adjusted models (OR: 1.835, p < 0.001), with LHR ≤ 1.257 serving as the reference. In subgroup analysis, all subgroups consistently demonstrated a significant association between increased LHR (all OR > 1).

The research results indicate that there is a non-linear positive correlation between LHR and the long-term risk of carotid plaques in middle-aged and elderly populations, suggesting that LHR may be an effective indicator for screening carotid plaques in grassroots middle-aged and elderly populations.

Congenital heart disease (CHD) is the most common birth defect, and its pathogenesis is closely related to the abnormal establishment of the left-right (LR) body axis, which highly depends on the ciliary function of the left-right organizer (LRO). This review systematically expounds the molecular pathways by which ciliary structural and functional abnormalities cause cardiac malformations by integrating multi-species model evidence. We believe that defects in multiple conserved genes (including CFAP45, ZIC3, FOXJ1, NEK3, APLNR, and microRNAs) disrupt ciliary assembly, motility, or signaling capacity, leading to the disappearance of the leftward nodal flow or mechanical sensing failure within the LRO. This further interrupts the left-specific calcium ion flicker and the activation of the Nodal-Pitx2 signaling cascade, ultimately resulting in failed cardiac looping and structural defects (such as ventricular septal defect and transposition of the great arteries). This review integrates transcriptional regulation, protein stability, miRNA-mediated fine regulation, and the planar cell polarity (PCP) pathway into a unified "cilia-LRO-heart" network and explores the molecular mechanisms of cilia in valve diseases and cardiac fibrosis. This not only deepens the understanding of the fundamental biological processes of heart development but also provides new molecular targets and theoretical frameworks for the genetic diagnosis and counseling of related congenital heart diseases.

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C), associated with SARS-CoV-2 infection share overlapping clinical and laboratory features, making differential diagnosis particularly challenging during the COVID-19 pandemic. Accurate distinction is essential due to differences in pathophysiology, management strategies, and cardiovascular outcomes. We report the case of a 7-year-old boy presenting with prolonged fever, mucocutaneous manifestations, arthritis, and elevated inflammatory markers following SARS-CoV-2 exposure. The clinical course demonstrated features compatible with both incomplete Kawasaki disease and MIS-C. Laboratory findings and cardiac biomarkers showed a mixed profile, while echocardiography and coronary imaging revealed the development of coronary artery aneurysms. Notably, a complex congenital coronary artery anomaly was incidentally identified during coronary evaluation. Although such anomalies are not considered independent risk factors for coronary aneurysm formation, their presence may complicate the interpretation of coronary findings in the setting of systemic inflammation. The patient showed a rapid and sustained clinical response to systemic glucocorticoid therapy without intravenous immunoglobulin administration; however, coronary artery aneurysms subsequently developed. This case highlights the diagnostic and therapeutic challenges at the interface of KD and MIS-C and underscores the importance of an integrated, individualized approach that incorporates clinical evolution, laboratory data, and detailed coronary assessment.

Myocarditis is a non-ischaemic myocardial injury caused by infectious agents, immune-mediated diseases, cardiotoxic drugs, and vaccines. Treatment options are largely supportive, with emphasis on close monitoring, exclusion of other diseases explaining symptoms, adherence to heart failure treatment recommendations, and consideration of etiology-directed interventions, if applicable, such as antiviral or immunosuppressive agents, steroids, discontinuation of antineoplastic therapy, and strategies to increase left ventricular (LV) ejection fraction (LVEF). In this context, cell-based therapies (CBTs) have emerged as a new therapeutic strategy and were believed to fill this gap. However, results were inconsistent across studies, which necessitates the need for rigorous systematic reviews to analyze available evidence comprehensively.

The review protocol was registered on the PROSPERO website, and the study was conducted in accordance with PRISMA regulations. Searches were conducted in Embase, CINAHL Plus via EBSCO host, Web of Science, Scopus, and PubMed. A total of 60 original papers published between 2004 and 2022 in 48 peer-reviewed journals were included in the meta-analysis to determine the efficacy of CBTs on the LV fractional shortening (LVFS), LVEF, capillary density (CD), inflammatory cell infiltration rate (ICIR), and fibrotic area (FA). The risk of bias (RoB) and study quality were assessed using the SYRCLE RoB tool and CAMARADES checklist, respectively. As the preliminary assessment indicated substantial heterogeneity among the included studies, a random-effects model was applied to pool effect sizes. Subgroup analyses were performed to explore potential sources of heterogeneity across studies. Publication bias was assessed by visual inspection of funnel plots for asymmetry and statistically evaluated using Egger's regression test.

In total, the adapted and optimized search strategy retrieved 14,503 records from five databases. The majority of studies exhibited an unclear or high risk of bias in several domains, particularly selection bias and performance bias. Quality assessment revealed that only four studies (6.7%) were classified as high quality and four (6.7%) as low quality, while the remaining 52 studies (86.7%) were rated as moderate quality, with scores ranging from 4 to 6. CBTs improved LVFS (%) by 7.17 [95 % CI: 5.67, 8.66], LVEF (%) by 9.00 [95 % CI: 7.03, 10.97], CD (capillaries/mm²) by 300.50 [95 % CI: 45.01, 555.99] and decreased ICIR (cells/mm²) and FA (%) by -178.99 [95 % CI: -225.91, -132.08] and -6.04 [95 % CI: -6.83, -5.25], respectively. However, significant heterogeneity between studies was maintained at I² = 84-99%.

Despite significant heterogeneity and moderate publication bias, the results were very encouraging, as reflected in the consistent effect directions across all studies in terms of cardiac function and histology. Overall, our results demonstrated the need for well-designed studies with adequate animal sample sizes, a standardized approach to reporting, and mechanistic investigations that directly link structural remodeling to functional recovery. Addressing these issues will be critical steps for conducting large-scale clinical trials.

This study aimed to assess the potential mediating role of metabolic syndrome (MetS) between depression and cardiovascular disease (CVD).

This population-based prospective cohort study analyzed data collected between March 2006 and December 2010 from 353,610 participants aged 37 to 73 years from the UK Biobank. Depression was assessed using self-reported questionnaires and linked hospital-based clinical depression diagnosis. MetS was defined as the presence of 3 or more of unhealthy waist circumference, dyslipidemia, hypertension, hyperglycemia and hypertriglyceridemia. Incident CVD was identified through linked hospital and death records. Counterfactual-based mediation analysis was conducted to estimate the mediating effect.

After an average follow-up of 15 years, 38424 CVD events occurred in 353,610 participants (55% women; mean age at baseline, 56 years). Study findings indicated a significant direct association between depression and CVD (HR = 1.310; 95% CI, 1.277-1.342). A significant indirect association was also observed between depression and CVD (HR = 1.035; 95% CI, 1.031-1.037), indicating that 12.9% of the association of depression with CVD was mediated by MetS. Among the components of MetS, unhealthy waist circumference showed the largest estimated mediated proportion (PM = 10.2%; NIE HR = 1.027). MetS accounted for a higher proportion of the association between depression and CVD in males (PM = 14.2%; NIE HR = 1.026), than females (PM = 11.2%; NIE HR = 1.034). Blood pressure mediated the association only in participants aged ≥55 years (PM = -2.2%).

MetS partially mediates the association between depression and CVD during midlife. Unhealthy waist circumference may be the most important potential target for preventive interventions.