Search Results (5,060)

Background/Objectives: Sugar-sweetened beverage (SSB) consumption has been linked to obesity, metabolic diseases, and rising healthcare costs. This study aimed to assess the impact of a 20% excise tax on SSBs in Brazil on obesity/overweight prevalence, seven musculoskeletal and cardiovascular diseases, and related healthcare costs, with their associated impacts on health inequalities. Methods: Using 2017/2018 Brazilian Household Budget Survey data for baseline consumption and own- and cross-price elasticities for taxed beverages, we estimated changes in caloric consumption for the entire population and for lower- and upper-income quartiles. The PRIMEtime dynamic individual-level simulation model projected body weight changes, lifetime Quality-Adjusted Life-Years (QALYs), healthcare costs (discounted at 5%), and disease cases (20-year horizon). Results: A 20% excise SSB tax was projected to reduce obesity prevalence by 1.7 percentage points in men and 1.5 percentage points in women, from baseline rates of 19.8% and 23.6%, respectively. Lifetime gains were estimated at 17,878 QALYs per million men and 12,181 per million women, alongside healthcare cost savings of Int$520 million. Impacts varied by income, with smaller health gains in the lowest quartile and higher among the wealthiest. Over 20 years, the tax could avert 1784 cases of type 2 diabetes mellitus/100,000 adults (52% in men) and 1070 cases of ischemic heart disease/100,000 adults (80% in men). Conclusions: A 20% excise SSB tax in Brazil could yield large health and cost benefits. With the recent approval of the Selective Tax under Complementary Law 214/2025, Brazil has a timely opportunity to translate these projected benefits into effective public health policy. Full article

Chronic kidney disease (CKD) and kidney failure significantly reduce patients’ quality of life and markedly increase cardiovascular risk and overall mortality. Disturbed metabolism of tryptophan (Trp) through kynurenine (KYN) pathways was implicated as an important factor in kidney damage and its complications. However, the expression of genes coding crucial enzymes of KYN pathway was not examined so far. The goal of the present study was to analyze the expression of Ido (indoleamine-2,3-dioxygenase), Kat1 (kynurenine aminotransferase 1), Kat2 (kynurenine aminotransferase 2), and Kmo (kynurenine-3-monooxygenase) genes in patients undergoing kidney failure with kidney replacement therapy (KFRT) treatment with either hemodiafiltration (HDF) or hemodialysis (HD) in relation to selected clinical and dialysis parameters. Our data imply that Ido, Kat1, and Kmo gene expression does not differ between KFRT patients with analyzed comorbidities, vascular access types, or diuresis occurrence. However, Ido and Kmo gene expression correlated with pre-dialysis concentration or reduction ratio (RR) of selected metabolites. Interestingly, patients treated with HDF manifested lower Kmo gene expression in comparison with patients treated by HD. Our study suggests that epigenetic factors do not exert noticeable impact on the KYN pathway enzymes expression in patients with KFRT. The advantageous effect of HDF vs. HD towards the KYN pathway genes expression has potential therapeutic implications, as it may reflect superiority of the former method in KFRT patients. Full article

Cardiometabolic diseases, including hypertension, type 2 diabetes, dyslipidemia, and obesity, along with their cardiovascular complications, remain leading causes of morbidity and mortality worldwide, imposing significant public health, economic, and societal burdens. Conventional pharmacological therapies often show limited efficacy and increased adverse effects because they do not account for the body’s intrinsic circadian rhythms, which regulate organ function, drug absorption, and metabolism. Chronopharmacology, which aligns treatment timing with these biological rhythms, offers a strategy to enhance therapeutic outcomes. This review presents a comprehensive analysis of chronopharmacology principles applied to cardiometabolic disease management, integrating molecular, physiological, and clinical perspectives. It examines how core clock genes and tissue-specific circadian patterns influence drug action and absorption and summarizes evidence-based time-optimized interventions for hypertension, diabetes, dyslipidemia, obesity, and multimorbid patients. Furthermore, the review highlights emerging innovations, including artificial intelligence-guided dosing, circadian-biomarker-informed therapy selection, and wearable digital devices for real-time monitoring of biological rhythms. By synthesizing mechanistic and clinical insights, circadian-aligned treatment strategies are shown to improve drug efficacy, reduce adverse effects, and support the development of precision, rhythm-based therapeutics, offering a practical framework for personalized cardiometabolic disease care. Full article

Objective: The study aims to evaluate the diagnostic and prognostic efficacy of gut-derived trimethylamine N-oxide (TMAO) as a molecular biomarker for heart failure (HF) in comparison to the N-terminal pro-B-type natriuretic peptide. Background: The clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is frequently affected by non-cardiac physiological variables, including adiposity, advanced age, and renal clearance rates. Consequently, there is a compelling need for additional biomarkers. This analysis investigates TMAO as a critical mediator within the gut–heart axis, reflecting systemic inflammation and myocardial fibrosis secondary to intestinal dysbiosis. Methods: A comprehensive literature search was conducted using PubMed. Keywords such as “trimethylamine N-oxide”, “heart failure”, “heart failure with preserved ejection fraction” and “N-terminal pro-B-type natriuretic peptide” were used. The inclusion criteria comprised original research and literature reviews describing the pathophysiological mechanisms and clinical utility of TMAO in the context of HF diagnosis and prognosis. Results: The analyzed literature suggests that TMAO functions as an independent predictor of major adverse cardiovascular events, correlating with all-cause mortality and rehospitalization risk across all HF phenotypes. Furthermore, data indicate that using TMAO alongside NT-proBNP measurements may predict patient risk more accurately, particularly in patients where natriuretic peptide interpretation is traditionally obscured by comorbidities such as diabetes mellitus and chronic kidney disease. Conclusions: Although NT-proBNP remains the gold standard for acute diagnosis, TMAO provides significant value for long-term clinical management. By serving as a metabolic–inflammatory indicator, TMAO complements standard diagnostic panels, offering deeper insights into the prognostic trajectory and the underlying intestinal barrier integrity of patients with HF. Full article

Background/Objectives: The widespread adoption of high-fat diets has contributed to a rising incidence of metabolic disorders and associated cardiovascular diseases. This trend exacerbates myocardial ischemia–reperfusion (I/R) injury following interventional or thrombolytic therapy for acute myocardial infarction, leading to higher mortality and heart failure in affected individuals with metabolic dysregulation, for whom effective interventions are limited. Nuciferine, which possesses anti-inflammatory, antioxidant, and metabolic regulatory properties, has shown potential in improving post-I/R cardiac function, yet its mechanism remains unclear. Methods: This study utilized an ex vivo mouse heart model perfused with high-glucose/high-fatty acid solutions to establish a metabolic stress condition mimicking key aspects of the diabetic milieu and to evaluate the underlying mechanisms of nuciferine. Complementarily, a model of lipotoxicity combined with hypoxia/reoxygenation (H/R) injury was established in human cardiomyocyte cells (AC16). Results: Nuciferine significantly improved post-I/R functional recovery and attenuated succinate accumulation, an effect comparable to the succinate dehydrogenase (SDH) inhibitor dimethyl malonate (DMM). Mechanistically, nuciferine bound to an SDH subunit, inhibiting its activity and subsequent reactive oxygen species (ROS) production via mitochondrial reverse electron transport (RET). It also activated Sirt1-dependent pathways, mitigating apoptosis and mitochondrial dysfunction in AC16 cardiomyocytes. The Sirtuin 1 (Sirt1) inhibitor selisistat (EX527) abolished nuciferine’s protection, while DMM mirrored its efficacy, underscoring nuciferine’s dual role in inhibiting SDH-mediated RET and activating Sirt1 in alleviating I/R injury under metabolic stress conditions. Conclusions: These findings suggest that nuciferine confers cardioprotection by simultaneously attenuating RET-related oxidative stress and activating Sirt1. Full article

Sympathetic nervous system (SNS) imbalance is a common pathological basis for cardiovascular diseases, non-alcoholic fatty liver disease, and diabetes. This review focuses on these diseases, analyzing two core mechanisms: excessive sympathetic excitation induced by endoplasmic reticulum stress (ERS) or autophagy dysfunction in key central nuclei (e.g., hypothalamus, rostral ventrolateral medulla); and ERS/autophagy abnormalities in peripheral target organs caused by chronic SNS overactivation. Existing studies confirm that chronic SNS overactivation promotes peripheral metabolic overload via sustained catecholamine release, inducing persistent ERS and disrupting the protective unfolded protein response (UPR)–autophagy network, ultimately leading to cell apoptosis, inflammation, and fibrosis. Notably, central ERS or autophagy dysfunction further perturbs autonomic homeostasis, exacerbating sympathetic overexcitation. This review systematically elaborates on SNS overactivation as a critical bridge mediating UPR–autophagy network dysregulation in central and peripheral tissues, and explores therapeutic prospects of targeting key nodes (e.g., chemical chaperones, specific UPR modulators, nanomedicine), providing a theoretical basis for basic research and clinical translation. Full article

Arterial stiffness encompasses the global structural and functional modifications that induce progressively increased vascular rigidity, whether associated with pathological cardiovascular or metabolic alterations or not. This narrative review highlights the comparative effects of physical exercise practices, current drug treatments, and approaches based on the use of medicinal plants on arterial stiffness, due to metabolic and/or blood pressure disorders. This review would provide up-to-date information for further experimental and clinical studies concerning the prevention/therapy of high glucose levels and vascular remodelling. Indeed, it is known that physical activities can reduce high blood glucose and blood pressure, allowing the prevention of arterial stiffness. Concerning conventional drugs, some are used to treat arterial stiffness, but their effectiveness is generally limited to treating components of the disease. Eighteen medicinal plant species, belonging to fourteen different botanical families, have potential activities against arterial stiffness in preclinical and/or clinical studies. Several plant extracts reduced the parameters implicated in vascular stiffness, such as the Pulse Wave Velocity, the Augmentation Index, and the Cardio–Ankle Vascular Index. Some plant extracts reduced arterial stiffness by primarily lowering glycemia and/or blood pressure in animal models, which has also been confirmed in humans. By reducing arterial stiffness, plant extracts or derived bioactive compounds not only improved vascular relaxation by enhancing Nitric Oxide production and/or antioxidant defences, but also inhibited inflammation-induced aortic remodelling and promoted elastin neo-synthesis. Polyphenols have often been identified as the main effective compounds involved in these beneficial effects. However, only a few studies explained the mechanisms associated. Full article

The gut microbiota is one of the key elements responsible for maintaining the body’s homeostasis. Its diverse composition affects, among others, the digestive and immune systems and also the circulatory system. Imbalances within the microbial community, referred to as dysbiosis, may lead to increased intestinal barrier permeability, chronic inflammation, and abnormal immune responses, which can be associated with the development of numerous diseases. Gut dysbiosis results in disturbances in the production of short-chain fatty acids, which exert anti-inflammatory effects, regulate blood pressure, and inhibit cardiac fibrosis. At the same time, it promotes the increased synthesis of trimethylamine N-oxide, a metabolite linked to inflammation, endothelial dysfunction, a higher risk of thrombosis, and the occurrence of arrhythmias. Additionally, small intestinal bacterial overgrowth (SIBO) may increase inflammation and contribute to metabolic and cardiovascular diseases (CVDs). The gut microbiota also influences the immune system through the production of neurotransmitters and modulation of T-cell activity, which may play a role in the development of autoimmune diseases. Reduced microbial diversity and an increased abundance of pathogenic bacteria are observed in individuals with hypertension and CVD, underscoring the importance of the microbiota as both a preventive and therapeutic factor. These findings highlight the crucial role of the gut microbiota in maintaining cardiovascular health and emphasize the need for further research into its modulation in the treatment of chronic diseases. Full article

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency, accumulation of globotriaosylceramide (Gb3), and progressive multiorgan involvement. Increasing evidence indicates that oxidative stress plays a central role in disease pathogenesis. This review aims to synthesize current knowledge on the molecular mechanisms underlying oxidative stress, the relevance of oxidative damage biomarkers, and potential therapeutic implications. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using terms related to Fabry disease, Gb3 metabolism, mitochondrial and endothelial dysfunction, inflammatory signaling, and oxidative stress markers. Clinical, experimental, and translational studies were included. Available data demonstrate that Gb3 accumulation disrupts mitochondrial function and activates NADPH oxidase, NF-κB, and MAPK signaling pathways, resulting in excessive production of reactive oxygen species. These processes contribute to cellular injury, particularly within the cardiovascular, renal, and nervous systems. Biomarkers such as malondialdehyde, 8-hydroxy-2′-deoxyguanosine, glutathione redox status, and antioxidant enzyme activities appear useful for assessing oxidative burden and monitoring therapeutic responses. Overall, current evidence underscores the pivotal role of oxidative stress in the progression of Fabry disease and highlights the need for further research into targeted antioxidant and disease-modifying therapeutic strategies. Full article

The triad association among type 2 diabetes mellitus (T2DM), metabolic associated fatty liver disease (MAFLD), and incretin secretion dysfunction, including GLP-1 (glucagon-like peptide-1) secretion dysfunction, maintains a critical cardiovascular risk and liver-related mortality. The aim of this study is to establish interactions between the GLP-1 plasma levels and metabolic syndrome clusters and adipokines profile (leptin, adiponectin, resistin) and proinflammatory cytokines (TNFα, IL-6, IL1β, IL-17) in diabetic subjects with or without MAFLD. The data revealed that insulin resistance (HOMA-IR) is present in all groups. MAFLD is more common in men than in women. The average FLI score in group IV was ≥70, confirming the diagnosis of MAFLD. The disorder of GLP-1 secretion is more pronounced in women than in men. HOMA-IR is negatively associated with plasma GLP-1 depletion in the MAFLD, T2DM, and MAFLD + T2DM groups. Adiponectin levels are decreased in all groups, as for GLP-1. In contrast, leptin, resistin, TNFα, IL-6, IL-1β, and IL-17 levels show an inverse correlation with GLP-1. GLP-1 accurately reflects metabolic and inflammatory status in subjects with MAFLD, T2DM, and diabetes—steatosis. The applied multivariate linear regression model confirms a highly significant association between MAFLD and GLP-1. It appears that plasma GLP-1 can be considered as biomarker in MAFLD and T2DM related to sex-gender disparities. Longitudinal studies are required to confirm these data. Full article

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological properties. Marine-derived toxins and venoms, including tetrodotoxin, ω-conotoxins, anthopleurins, palytoxin, brevetoxin, aplysiatoxin, and asterosaponins, exert cardioprotective effects through diverse mechanisms such as modulation of ion channels, inhibition of sympathetic overactivity, antioxidative actions, and enhancement of myocardial contractility. These properties make them potential candidates for addressing various CVD manifestations, including arrhythmia, hypertension, ischemia–reperfusion injury, and heart failure. However, despite their therapeutic promise, the clinical application of these marine compounds remains limited due to poor tissue selectivity, narrow therapeutic indices, proinflammatory activity, and limited metabolic stability. Structural modifications, advanced drug delivery platforms, and in vivo validation studies are crucial for overcoming these challenges. This review highlights the pharmacological actions, molecular targets, and cardiovascular relevance of selected marine toxins and venoms while also addressing key translational barriers. Advances in biotechnology and peptide engineering are enabling the safer and more targeted use of these compounds. Collectively, marine-derived toxins and venoms represent a largely untapped but highly promising frontier in cardiovascular drug discovery. Strategic research focused on elucidating mechanisms, optimizing delivery, and translating clinical applications will be critical to unlocking their full therapeutic potential. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are associated with multiple factors, including oxidative stress, mediated endothelial dysfunction, vascular inflammation, and atherothrombosis. Although traditional antioxidant supplementation (such as vitamins C, E, and β-carotene) has shown promising results in rigorous animal model studies, it has consistently failed to demonstrate clinical benefit in most human trials. Consequently, there is a substantial unmet need for novel paradigms involving mechanistically and biologically relevant pharmaceutical-grade antioxidant therapies (“next-generation antioxidants”). Rapid advancements in redox biology, nanotechnology, genetic modulation of redox processes, and metabolic regulation have enabled the development of new antioxidant therapeutics, including mitochondrial-targeted agents, NADPH oxidase (NOX) inhibitors, selenoprotein and Nrf2 activators, engineered nanoparticles, catalytic antioxidants, and RNA-based and gene-editing strategies. These interventions have the potential to modulate specific oxidative pathways that contribute to CVD pathogenesis. This review provides a comprehensive assessment of current oxidative stress–modulating modalities and their potential to inform personalized cardiovascular prevention and treatment strategies. Full article

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

Diet plays a central role in shaping the composition and metabolic activity of the oral microbiota, thereby influencing both oral and systemic health. Disturbances in this delicate host–microbe balance, triggered by dietary factors, smoking, poor oral hygiene, or antibiotic use, can lead to microbial dysbiosis and increase the risk of oral diseases such as periodontitis, as well as chronic systemic disorders including diabetes, cardiovascular disease, Alzheimer’s disease, and certain cancers. Among dietary contaminants, exposure to toxic heavy metals such as cadmium (Cd), lead (Pb), mercury (Hg), nickel (Ni), and arsenic (As) represents an underrecognized modifier of the oral microbial ecosystem. Even at low concentrations, these elements can disrupt microbial diversity, promote inflammation, and impair metabolic homeostasis. Saliva has recently emerged as a promising, non-invasive biofluid for monitoring nutritional status and early metabolic alterations induced by diet and environmental exposures. Salivary biomarkers, including metabolites, trace elements, and microbial signatures, offer potential for assessing the combined effects of diet, microbiota, and toxicant exposure. This review synthesizes current evidence on how diet influences the oral microbiota and modulates susceptibility to heavy metal toxicity. It also examines the potential of salivary biomarkers as integrative indicators of nutritional status and metabolic health, highlights methodological challenges limiting their validation, and outlines future research directions for developing saliva-based tools in personalized nutrition and precision health. Full article

Kidney aging is receiving growing attention in middle- to high-income societies due to increasing longevity in general population. Chronic Kidney Disease (CKD) has been widely accepted as a major non-communicable human disease affecting over 10% of the adult population in industrialized countries. CKD is mainly caused by metabolic and cardiovascular disorders such as diabetes mellitus and hypertension, disproportionally affecting older people, whereas natural kidney aging is driven by age-dependent systemic and renal low-grade inflammation. Interleukin-6 (IL-6) is the key cytokine mediating age-related inflammation. At the same time, IL-6 has been implicated in the pathophysiology of cardiovascular and renal disorders as a major pro-inflammatory cytokine. Thereby, IL-6 is placed at the intersection between natural and pathophysiological kidney aging, and the latter accelerates systemic aging and substantially limits life quality and expectancy. Growing clinical availability of IL-6 inhibitors for treatment of autoimmune and autoinflammatory disorders demands clarification of potential renal consequences as well. Available data suggests that IL-6 inhibition may be renoprotective in some kidney disorders, but the setting of kidney aging has received only minor attention. The present review focuses on the known effects of IL-6 associated with natural or pathophysiological renal aging. Full article