Heart failure (HF) is a heterogeneous condition with a prevalence of about 1-3% in the population worldwide (percentage expected to rise), related to a significant clinical and economic burden. However, despite medical advancements in HF management, difficulties in facing this condition still persist, as the etiology and phenotype largely differ between patients. Thus, the identification of further key biomarkers remains attractive. One area of interest in recent years has focused on the role of lipids in HF pathophysiology and its clinical manifestations. In this context, ceramides, complex bioactive lipids with activity in key pathways related to stress response, cellular growth, proliferation, differentiation, apoptosis, oxidative stress, inflammation, and energy production, may be important in the HF scenario, primarily for the development and application of new therapeutic strategies targeting ceramide species. Accordingly, this review aims to discuss the role of ceramides in HF pathophysiology and clinical progression in view of available evidence, focusing on the possibility of therapeutic tools for improving cardiac function and outcomes in HF by modulating ceramide signaling and metabolism.

Cardiovascular diseases (CVDs) remain the primary cause of human morbidity and mortality in the world. Inflammation, oxidative stress, and vascular remodeling are the key factors that make CVDs worse. The nuclear factor κB (NF-κB) signaling pathway is a major regulator in the progression of CVDs. NF-κB activates wrongly, induces the secretion of pro-inflammatory cytokines (including TNF-α, IL-6, and IL-1β), and enhances reactive oxygen species (ROS) generation. These accelerate endothelial dysfunction, myocardial damage, and atherosclerotic plaque development. Natural products are structurally diverse, multi-targeted, and low toxicity. They offer a promising way to prevent and treat cardiovascular disease by modulating the NF-κB signaling pathway. This review summarizes the recent studies about using natural products (including flavonoids, terpenoids, alkaloids, polyphenols, and polysaccharides) to treat CVDs through the NF-κB pathway, with a critical analysis of evidence strength according to CVDs indication (atherosclerosis, myocardial ischemia/reperfusion injury, pulmonary arterial hypertension, etc.) and study type (in vitro, in vivo animal, and human clinical research). We detail their molecular mechanisms, such as inhibiting the nuclear translocation of NF-κB p65, downregulating IκB phosphorylation, blocking upstream signaling (e.g., TLR4/MyD88, PI3K/Akt, MAPK), and affecting with other pathways (e.g., Nrf2/HO-1, SIRT1) to reduce inflammation and oxidative stress together. We also detail the effects of these natural products in various CVDs models, including atherosclerosis, hypertension, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, and pulmonary arterial hypertension, highlighting the characteristics of their treatments. Finally, we discuss the challenges of bringing natural products into the clinic and share some ideas to solve difficulties, with an in-depth critical analysis of the translational bottlenecks (poor bioavailability, unclear structure-activity relationships, incomplete mechanistic elucidation, and lack of large-scale clinical trials) and their underlying causes across different natural product classes. In summary, this review offers new perspectives on developing natural product-based therapies targeting the NF-κB signaling pathway for CVDs. It offers useful references for both preclinical studies and clinical applications.

Ginkgetin (GK) is a naturally occurring biflavonoid predominantly isolated from Ginkgo biloba and has attracted increasing attention because of its broad pharmacological activities. Structurally, GK belongs to the 3'-8″-linked biflavone subclass, which distinguishes it from other biflavonoids like amentoflavone (the parent compound of this subclass) and its monomeric counterparts such as apigenin. This unique C-C linked dimeric architecture confers distinct molecular planarity and lipophilicity, contributing to its enhanced membrane permeability and multitarget engagement capabilities. GK has been shown to exert pleiotropic biological effects in preclinical studies, including anti-inflammatory, antioxidant, antifibrotic, anticancer, neuroprotective, cardioprotective, metabolic regulatory and antibacterial activities. Mechanistically, preclinical evidence indicates that GK functions as a multitarget modulator of key signaling pathways involved in oxidative stress, inflammation, cell death and tissue remodeling, such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1), nuclear factor kappa-B(NF-κB), Janus kinase/signal transducer and activator of transcription(JAK/STAT), mitogen-activated protein kinases(MAPKs), AMP-activated protein kinase/mechanistic target of rapamycin(AMPK/mTOR), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) and cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING). Notably, GK has been observed to display context-dependent regulation of cell fate decisions, including apoptosis, autophagy and ferroptosis, thereby enabling the selective elimination of pathological cells while preserving normal tissue function. Preclinical studies further demonstrate that GK exhibits therapeutic potential across diverse disease systems, including cancer, metabolic disorders, cardiovascular diseases, neurological disorders and musculoskeletal diseases. In addition, emerging evidence highlights its antibacterial and antivirulence properties through the inhibition of biofilm formation and quorum sensing. It is crucial to note, however, that this promising profile is predominantly derived from preclinical studies, and clinical evidence in humans remains to be established. Despite these promising findings, the clinical translation of GK remains limited by challenges related to pharmacokinetics, bioavailability and druggability. This review systematically summarizes the chemical characteristics, pharmacological activities and molecular mechanisms of GK, with an emphasis on its multitarget actions and therapeutic potential across disease systems, and discusses current limitations and future perspectives to facilitate the rational development of GK-based interventions.

Background/Objectives: Percutaneous coronary intervention (PCI) effectively restores coronary flow in acute myocardial infarction (AMI), but myocardial ischemia-reperfusion injury (MIRI) remains a major prognostic determinant. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown cardiovascular protective effects, yet its association with MIRI is unclear. This study aimed to investigate the relationship between serum MOTS-c levels and MIRI in AMI patients. Methods: Seventy-two AMI patients undergoing PCI were enrolled and divided into MIRI (n = 34) and non-MIRI (n = 38) groups. Clinical data and MOTS-c levels in peripheral serum and intracoronary blood were compared. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed to identify MIRI predictors. Results: The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade and adverse event incidence (all p < 0.05). Postoperative peripheral serum MOTS-c levels were significantly lower in the MIRI group than in the non-MIRI group (p < 0.05), while preoperative peripheral and intracoronary MOTS-c levels showed no significant differences between groups. Multivariate logistic regression identified postoperative peripheral MOTS-c levels (OR = 0.986, 95%CI: 0.976-0.996) and preoperative TIMI grade ≥ 1 (OR = 0.036, 95%CI: 0.004-0.309) as independent protective factors for MIRI, whereas serum creatinine was identified as an independent risk factor. ROC analysis demonstrated that postoperative peripheral MOTS-c levels predicted MIRI with an area under the curve of 0.648. Conclusions: Postoperative peripheral serum MOTS-c levels represent an independent protective factor against MIRI in patients with acute myocardial infarction and suggest a potential predictive value for MIRI, although its clinical utility as a standalone predictor requires further validation through dynamic monitoring and larger-scale studies. This finding may offer a potential novel biomarker and therapeutic direction for MIRI.

Background/Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits beyond glycemic control, yet the specific biological pathways potentially linking SGLT2 inhibitor exposure to cardiovascular outcomes after acute myocardial infarction (AMI) remain incompletely characterized. Two biologically plausible pathways, serum uric acid (SUA) reduction and renal functional preservation, have been proposed, but not directly compared in a unified analytical framework. This study aimed to explore whether associations between SGLT2 inhibitor exposure and recurrent post-AMI outcomes may be more strongly linked to SUA reduction and to renal functional changes, using a hypothesis-generating causal mediation analysis. Methods: This retrospective observational cohort study included 142 consecutive patients hospitalized for AMI who underwent percutaneous coronary intervention (PCI) during the index hospitalization, reflecting standard-of-care management for AMI in this tertiary center. Patients were categorized by SGLT2 inhibitor exposure (n = 57) vs. controls (n = 85). Both diabetic (47.2%) and non-diabetic (52.8%) patients were included. The primary endpoint was change in SUA (ΔUA); the secondary endpoint was myocardial infarction (MI) recurrence. Causal mediation analysis with nonparametric bootstrap simulation tested both mechanistic pathways. Results: SGLT2 inhibitor therapy was associated with significant SUA reduction (ΔUA = -0.99 mg/dL vs. +0.56 mg/dL in controls; p < 0.001), consistent across diabetic and non-diabetic subgroups and independent of AMI recurrence. Each 1 mg/dL decrease in SUA was associated with lower odds of recurrent MI in the initial model (β = -0.25; p = 0.041). However, after incorporation of renal functional change, the uric acid-mediated pathway lost significance (ACME p = 0.462), whereas the renal-mediated pathway remained significant (ACME p = 0.038). Serum creatinine change emerged as the strongest independent predictor of MI recurrence (β = 2.22; p = 0.015). Conclusions: The findings are more consistent with a renal-mediated pathway than with an independent uric acid-mediated pathway in explaining the observed associations between SGLT2 inhibitor exposure and recurrent post-AMI outcomes. These hypothesis-generating results from a retrospective design warrant prospective validation.

The ratio of high-sensitivity C-reactive protein (hs-CRP) to Serum albumin (SA) (hs-CRP/SA) is emerging as a new potential biomarker capable of stratifying cardiovascular risk in patients with chronic HF (CHF), particularly the risk of major adverse cardiovascular events (MACEs). Objectives: The aim of this study was to evaluate the long-term prognostic value of the hs-CRP/SA ratio on the risk of MACEs in a population of outpatients with CHF. Methods: In this retrospective observational study, 500 patients were enrolled and were stratified into two groups based on the median value of the hs-CRP/SA ratio: 249 patients with hs-CRP/SA < 1.19 and 251 patients with hs-CRP/SA ≥ 1.19. Results: During median follow-up of 5.2 years, 3.6 MACEs/100 patients/year were detected; patients with hs-CRP/SA ≥ 1.19 had a MACE incidence of 5.9 events per 100 patient-years, compared with 1.2 events per 100 patient-years in those with hs-CRP/AS < 1.19 (p < 0.001). Multivariate analysis confirmed that hs-CRP/SA ≥ 1.19 was associated with an approximately 6.5-fold increased risk of new MACEs (HR 6.513, 95% CI 3.928-10.797; p < 0.001). Conclusions: The hs-CRP/SA ratio is confirmed as a powerful prognostic marker in patients with CHF, associated with a significantly increased risk of MACEs.

Telemedicine, driven by the Internet of Things (IoT) and wireless connectivity, is essential for managing cardiovascular diseases, where hypertension remains the primary risk factor. In preclinical research, rabbits are superior biological models compared to rodents due to their human-like lipid metabolism. However, continuous blood pressure monitoring in this species remains challenging. The gold-standard technique (direct carotid catheterization) requires terminal procedures, and indirect methods (Doppler, oscillometric) show limited agreement with direct measurements. Furthermore, commercially available implantable telemetry platforms, while enabling real-time monitoring in freely moving animals, require costly surgical implantation, specialized proprietary hardware, and post-operative recovery periods that may confound early hemodynamic data. To address these limitations, this study presents a low-cost, customizable, and minimally invasive monitoring system utilizing a pressure transducer in the central auricular artery. The device integrates an ESP32 microcontroller with IoT technology for digital signal processing and seamless wireless data transmission to the ThingSpeak cloud platform. Unlike implantable telemetry, the proposed approach avoids surgical implantation and its associated costs and recovery time, while still enabling continuous, real-time hemodynamic tracking throughout the experimental period. A pilot evaluation against the BIOPAC MP100 reference (carotid artery) demonstrated relative errors of 1.60% for mean arterial pressure, 8.58% for systolic blood pressure, and 2.43% for diastolic blood pressure. By reducing invasiveness and enhancing remote data accessibility, this system provides a promising framework for the preclinical evaluation of antihypertensive agents and cardiovascular mechanisms, bridging the gap between edge computing and remote clinical diagnostics.

Cirrhosis is no longer viewed solely as an isolated hepatic disorder but rather as a complex multisystemic disease that affects cardiovascular, renal, pulmonary, metabolic, and immune systems. One of its most clinically relevant but under-recognized consequences is cardiac dysfunction, manifesting as cirrhotic cardiomyopathy, portopulmonary hypertension, right ventricular (RV) failure, and impaired myocardial strain. Oxidative stress (OS) has recently emerged as a fundamental mechanistic link between hepatic fibrogenesis and myocardial remodeling, acting through mitochondrial injury, NADPH oxidase activation, nitric oxide dysregulation, iron-mediated ferroptosis, and inflammatory cytokines. These alterations lead to diastolic dysfunction, autonomic imbalance, myocardial fibrosis, electrophysiological abnormalities (including QTc prolongation), and impaired RV-pulmonary artery coupling. Redox biomarkers such as malondialdehyde (MDA), NOX2-derived peptides, GSH/GSSG ratio, sST2, NT-proBNP, and 8-isoprostanes hold promise in detecting early subclinical cardiac involvement in cirrhosis. Novel antioxidant therapies, including mitochondrial-targeted molecules, NOX inhibitors, and ferroptosis blockers, may improve myocardial remodeling and hemodynamic stability. This review explores the central role of redox imbalance in the cardiohepatic syndrome and its potential utility in diagnosis, monitoring, and therapy.

Constrictive pericarditis (CP) is a diagnostic challenge due to its nonspecific and insidious presentation.

A 38-year-old man presented with bilateral lower limb edema and exertional dyspnea.

Cardiac magnetic resonance imaging demonstrated pericardial thickening, late gadolinium enhancement, and interventricular septal bounce. Tuberculous CP was considered based on imaging findings, positive interferon-gamma release assay, therapeutic response, and epidemiologic background.

The patient was treated with anti-tuberculosis therapy without surgical pericardiectomy.

Follow-up imaging showed near-complete resolution of pericardial thickening and effusion, with sustained clinical improvement.

This case highlights the value of cardiac magnetic resonance imaging in the early diagnosis of inflammatory CP and supports the role of medical therapy in selected patients.

Epilepsy, ischemic stroke, and depression, as common neurological diseases, pose a serious threat to human health. Although vagus nerve stimulation (VNS) has been applied in the treatment of these diseases, its exact mechanism of action remains unclear. This study aims to deeply analyze the relationships between the core target genes of VNS and epilepsy, ischemic stroke, and depression by integrating network pharmacology, bioinformatics, and Mendelian randomization. The results showed that, compared with the control group, 159 differentially expressed genes were identified in the VNS-treated group. These genes were involved in biological processes such as "protein-RNA complex organization" and are enriched in metabolism-related pathways such as the "AMPK signaling pathway." There were 73, 54, and 108 overlapping genes between VNS-related genes and genes related to epilepsy, ischemic stroke, and depression, respectively. Through network analysis and Mendelian randomization analysis, several core genes that may play a protective role in the corresponding diseases were identified, such as CPT1A, SUCLG1, IMMT, IVD, and PSMA2. This study has revealed the potential molecular mechanisms possibly involved in VNS treatment of these neurological diseases. The findings offer crucial clues for further in-depth study of VNS treatment mechanisms, and may boost the development of more precise and effective treatment strategies.