Search Results (256)

Among cardiovascular diseases, myocardial infarction (MI) has become one of the leading causes of mortality worldwide, and the prevalence is anticipated to rise considerably in the coming years. Within non-surgical procedures, chemical drugs, including diuretics, vasodilators, calcium channel blockers, ꞵ blockers, angiotensin converting enzyme inhibitors, are now a well-established option to treat MI progression. However, these drugs are not developed to mitigate oxidative stress directly, which has been recently proven to contribute to MI advancement. Naturally occurring antioxidant compounds possess promising cardioprotective properties and have the potential to be used both as lead compounds for finding novel drugs and complementary therapy to manage MI. While some of them, namely quercetin, puerarin, α-lipoic acid, and curcumin, have already made their way up to clinical trials, numerous compounds have not been sufficiently investigated clinically. To develop and formulate natural antioxidant compounds as drugs against MI, it is crucial to comprehend their underlying mechanisms of cardio-protective activities and structure–activity relationships (SARs). This comprehensive review sheds light on the contribution of oxidative stress in the pathogenesis and progression of Myocardial Infarction, and highlights the cardio-protective roles of 51 natural antioxidant compounds along with their mechanistic insights and SAR. Full article

Background: Real-world kidney and metabolic responses to semaglutide in type 2 diabetes (T2D) and chronic kidney disease (CKD) remain poorly characterised, particularly in Middle East and North Africa (MENA) region. Methods: We conducted a retrospective, single-centre, paired-cohort study at a secondary care hospital in UAE. Adults with T2D and predominantly mild CKD newly initiated on subcutaneous semaglutide were included. Single-arm design without comparator; findings describe biomarker trajectories and cannot establish causality. Primary outcomes were within-participant six-month changes in serum creatinine, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (uACR). Results: A total of 324 patients were analysed (mean age 55.3 ± 12.4 years; 66.0% female; BMI 36.1 ± 6.9 kg/m²; median HbA1c 8.3% [IQR 7.2–10.0]; eGFR 87.0 ± 25.8 mL/min/1.73 m²; KDIGO G1–G2 in 82.7%; A2 92.6%, A3 4.6%). At six months, BMI fell by 2.0 kg/m² and HbA1c by a median 2.0%; 52.0% achieved ≥5% BMI reduction and 87.2% achieved ≥0.5% absolute HbA1c reduction. Serum creatinine decreased by 3.6 µmol/L and eGFR rose by 3.7 mL/min/1.73 m²; given concurrent weight loss, these changes likely reflect reduced creatinine generation rather than true filtration improvement. A ≥30% eGFR decline occurred in only 0.9%. Geometric mean uACR fell by 19.8%; among participants with baseline uACR ≥ 30 mg/mmol, 66.7% achieved ≥30% uACR reduction. KDIGO G-category improved in 17.3% and was stable in 76.8%; the A-category remained stable in 95.7%. Conclusions: In adults with T2D, mild CKD, and substantial obesity, semaglutide was associated with clinically meaningful improvements in weight, glycaemia, and albuminuria over six months, supporting it as part of a layered cardio-renal protective strategy in routine care. Full article

Background: Stroke remains a leading cause of death and long-term disability worldwide. Sleep disturbances are increasingly recognized as potential factors influencing recovery after stroke. Therefore, in this study we examined the associations of sleep disturbances and metabolic markers with post-stroke outcomes. Methods: We conducted a retrospective study of adult patients with stroke-related presentations. The primary analysis included 270 patients with follow-up mRS data. Extracted variables included demographics, vascular risk factors, stroke subtype, imaging findings, sleep features, and selected laboratory markers. Functional outcome was classified as favorable, mRS 0–2, or unfavorable, mRS 3–6. Recurrent stroke burden was analyzed as 0–1 versus ≥2 documented events. Associations and predictive performance were assessed using group comparisons, LASSO logistic regression, and random forest models with repeated 10-fold cross-validation. Results: Among 270 stroke patients, 214 (79.3%) had favorable outcomes and 56 (20.7%) had unfavorable outcomes. Sleep disturbances were common, especially nocturnal awakenings (59.6%), increased sleep apnea risk (44.4%), circadian rhythm disturbances (28.9%), and insomnia (23.7%). Unfavorable outcomes were linked to older age, cardio-aortic embolism, large vessel/cortical stroke, abnormal vascular imaging, insomnia, and lower HDL. In LASSO analysis, age, steno-occlusive/atherosclerotic imaging, cardio-aortic embolism, and insomnia predicted unfavorable outcome, while HDL was protective. For recurrent stroke, small artery occlusion and hypertension with diabetes were retained. In predictive modeling, the best random forest model showed good discrimination AUC values of 0.791 ± 0.0126. Conclusions: Poorer stroke outcomes were associated with vascular factors, insomnia, and low HDL; recurrent events were mainly associated with small artery occlusion. Full article

Background/Objectives: Composite endpoints are commonly used in chronic kidney disease (CKD) trials to enhance statistical efficiency but may not reflect clinically meaningful outcomes. We assessed agreement between composite endpoints and key components using the bias attributable to composite outcome (BACO) index and explored determinants of variability. Methods: We performed a meta-epidemiological analysis of randomized controlled trials evaluating sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists in CKD. BACO was defined as the ratio of the log-hazard ratio for the composite endpoint to that of the reference outcome (kidney failure or cardiovascular death), with variance estimated using the delta method. Determinants were analyzed using inverse-variance weighted mixed-effects meta-regression. Results: Eight trials comprising 38 composite endpoints were included. Higher reference-event rates were associated with higher BACO values overall (β: 0.06, 95% CI: 0.02; 0.10) and in kidney failure-referenced analyses (β: 0.07, 95% CI: 0.02; 0.12). Stronger composite treatment effects correlated with higher BACO (β: −1.07, 95% CI: −1.84; −0.30). The number of components and follow-up duration showed no significant association. In cardiovascular death-referenced models, BACO was associated with trial size (β: 0.12 per 1000 participants), mean age (β: −0.04 per 10 years), and female proportion (β: 0.09 per 10% increase). Conclusions: Agreement between composite endpoints and clinically relevant outcomes is driven by the relative frequency and treatment responsiveness of component events rather than endpoint complexity. Composite endpoints in which clinically important outcomes are infrequent may not reliably reflect treatment effects, underscoring need for clinically aligned endpoint strategies. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, and residual inflammatory risk persists despite optimal lipid and glucose control. Emerging evidence indicates that metabolic reprogramming within immune cells constitutes a central driver of cardiovascular immune injury. In this review, we propose a unifying framework in which glyco-lipotoxicity acts as a primary metabolic trigger, inducing mitochondrial dysfunction, oxidative stress, and activation of the NLRP3 inflammasome and cGAS–STING pathways. Hyperglycaemia and dyslipidaemia reshape intracellular metabolic circuits, enhancing glycolysis and disrupting oxidative phosphorylation, thereby promoting sustained pro-inflammatory phenotypes. Crucially, metabolic intermediates function as cofactors for epigenetic remodelling. This establishes trained immunity in both circulating innate immune cells and haematopoietic stem/progenitor cells, which serves as the cellular basis for persistent metabolic memory. This persistent immunometabolic imprint amplifies sterile inflammation and accelerates vascular and myocardial remodelling. Furthermore, these processes are systemically propagated through cross-organ communication networks, including the heart–adipose, gut–heart, and cardio-hematopoietic axes, forming a multidimensional inflammatory amplification loop. We also summarise emerging therapeutic strategies targeting the metabolic–epigenetic axis, aiming to reverse maladaptive trained immunity and mitigate residual CVD risk. By integrating immunometabolism, epigenetic regulation, and organ crosstalk, this review highlights metabolic reprogramming as a pivotal mechanistic nexus and potential precision target for cardiovascular protection. Full article

The prevalence of diabetes and heart failure rises sharply with age, and their coexistence amplifies cardiovascular and renal risk. Elderly patients display unique clinical and biological profiles characterised by frailty, multimorbidity, and pharmacodynamic variability that challenge conventional treatment strategies. Sodium–glucose co-transporter-2 inhibitors (SGLT2i) have emerged as a cornerstone of cardio–renal–metabolic protection, with the most consistent cardiovascular benefit being the reduction in heart failure hospitalisation, whereas effects on cardiovascular death and major adverse cardiovascular events vary according to baseline cardiovascular risk, heart failure phenotype, diabetic status, and trial design. However, real-world use among the elderly remains limited due to concerns about tolerability, polypharmacy, and cost. This review analyses the pharmacological rationale and evidence base for SGLT2i therapy in older adults, highlighting mechanisms beyond glucose control, quantitative data from pivotal trials, and practical issues for geriatric implementation. Full article

Background: Cancer cachexia is a serious condition during the last stages of the disease, which is characterized by the loss of muscle and fat mass in patients with cancer. There are no effective treatments for cancer cachexia, and new treatment interventions are urgently needed. We have previously demonstrated that 5 mg/kg/day bisoprolol and 1.7 µg/kg/day ARA 284, a small non-erythropoietic tissue protective peptide, separately have positive effects in a rat model of cancer cachexia. Methods: We investigated the compound effects of both bisoprolol and ARA 284 by targeting multiple pathways in the Yoshida hepatoma rat model of cancer cachexia. Rats were randomly allocated to one of the following treatment groups: bisoprolol (5 mg/kg/day), ARA 284 (1.7 µg/kg/day), a 25% combination (1.25 mg/kg/day bisoprolol + 0.425 µg/kg/day ARA 284), a 75% combination (3.75 mg/kg/day bisoprolol + 1.275 µg/kg/day ARA 284), or placebo. Results: The combination of 3.75 mg/kg/day bisoprolol and 1.275 µg/kg/day ARA 284 showed the strongest overall effects compared with the respective effective monotherapies, respectively, or placebo across multiple endpoints, including body weight, lean mass, food intake, spontaneous activity, and cardiac function in a rat model of cancer cachexia (p < 0.01, respectively). Furthermore, this combination therapy had the strongest effects on survival against the placebo (hazard ratio 0.08, 95% confidence interval 0.04 to 0.17, p < 0.001). Conclusions: Our findings show that the combination of bisoprolol and ARA 284 is beneficial in a hepatoma cachexia model and may provide greater overall effects than either monotherapy alone. Full article

Background/Objectives: Cardiovascular diseases (CVDs) and cancer remain major global health challenges and are among the leading causes of mortality worldwide, including in Kuwait. Medicinal plants are important sources of bioactive compounds with therapeutic potential. This study aimed to identify the phytochemical constituents of Curcuma longa L. root extract and evaluate their potential cardioprotective and anticancer activities using integrated computational approaches. Methods: Phytochemical profiling of Curcuma longa root extract was performed using gas chromatography–mass spectrometry (GC–MS). The identified compounds were evaluated through molecular docking against selected cardiovascular- and cancer-related targets, including HMG-CoA reductase, phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 6 (CDK6), and HER2 kinase receptors. Protein–ligand interactions were analyzed to determine binding stability. Biological activity prediction and pharmacokinetic properties were assessed using PASS prediction and SwissADME tools, while density functional theory (DFT) calculations were conducted to investigate electronic and quantum chemical characteristics associated with ligand reactivity. Results: GC–MS analysis identified seventeen phytochemical constituents with retention times ranging from 7.57 to 32.70 min. The major compounds detected were 2-oxo-cyclooctaneacetic acid (30.88%), curlone (20.99%), and tumerone (13.85%). Molecular docking revealed favorable binding affinities for α-curcumene, caryophyllene, bergamotene, cyclohexene derivatives, tumerone, curlone, and (6R,7R)-bisabolone against the selected targets, with interaction profiles comparable to reference drugs. PASS and SwissADME analyses indicated promising biological activities, acceptable drug-likeness, and favorable pharmacokinetic properties. DFT analysis demonstrated that curlone and tumerone possessed stable electronic configurations and favorable reactivity profiles. Conclusions: The findings suggest that bioactive compounds from Curcuma longa may serve as promising lead candidates for the development of cardioprotective and anticancer agents. However, further experimental validation through in vitro and in vivo studies is required to confirm these computational predictions. Full article

Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K/Akt, MAPK, NF-κB, and Nrf2. The interplay between these pathways underpins DHM’s efficacy across disease models. Furthermore, we highlight structure–activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions. Full article

The obesity–metabolic syndrome–diabetes continuum is driven by interconnected mechanisms including insulin resistance, dysfunctional adiposity, chronic inflammation and progressive cardio–renal–metabolic injury. This triggered a need for therapies that extend beyond glucose lowering alone. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as disease-modifying drugs include weight loss, cardiovascular risk reduction, glycemic control and renal protection. However, treatment burden, adherence issues and access restrictions may limit the long-term effects of injectable formulations. One significant translational development that aims to close this gap is oral GLP-1-based treatments. In this review, we examine the mechanistic rationale, formulation science and clinical development of oral GLP-1 RAs. Oral semaglutide is presented as the first validated proof of concept for systemic peptide delivery by the gastrointestinal route. The biological barriers to oral peptide absorption, including enzymatic degradation, low epithelial permeability, pharmacokinetic variability and epithelial safety constraints, are critically discussed. Enabling technologies such as SNAC-based gastric absorption, nanocarriers, mucoadhesive systems and stability-optimization platforms are evaluated. Evidence from the PIONEER program and related studies demonstrating meaningful glycemic and weight-loss efficacy, acceptable safety and clinical utility in patients with type 2 diabetes and chronic kidney disease is further synthesized. Beyond first-generation oral peptide platforms, we discuss the emerging landscape of non-peptide oral GLP-1 RAs, dual and triple incretin agonists, precision dosing strategies and model-informed drug development. Oral GLP-1-based therapeutics are shifting from a formulation breakthrough to a broader translational strategy for disease modification across the obesity–metabolic syndrome–diabetes continuum. Long-term renal outcomes, access and implementation barriers remain important priorities for future research. Full article

Coffee is a very popular psychoactive beverage with a complex composition. Besides its stimulant effect due to caffeine, it contains several bioactive compounds with antioxidant properties and potent metabolic activity. Its clinical efficacy is fundamentally determined by the bioavailability and metabolic fate of its constituents. The bioactive components of coffee, such as polyphenols, melanoidins, phytosterols, biogenic amines, and carotenoids, have notable antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to present the main bioactive components of coffee, their biological effects, mechanisms of action, and the influence of preparation methods and individual variability on metabolic outcomes in common chronic diseases. The data are synthesized from clinical, prospective, and interventional studies to examine how processing variables and biological metabolism influence the health-promoting potential of coffee antioxidants. Brewing methods like hot filtration optimize the extraction of these antioxidants. Individual clinical outcomes are further modulated by genetic polymorphisms and gut microbiota variability, which influence the activation of the cellular Nrf2 antioxidant defense pathway. Full article

Landmark epidemiological studies and clinical trials, such as the Seven Countries Study, the Lyon Diet Heart Study, the PREDIMED Study and the CORDIOPREV Study, have shown significant reductions in cardiovascular events in those following the Mediterranean diet (MD). The aim of the present work is to summarize the most robust available evidence and the major biological pathways underlying the protective effects of the MD, with particular emphasis on the role of PAF inhibitors. Mechanistically, MD functions through a complex synergy of antioxidant, anti-inflammatory, and antithrombotic effects that collectively improve lipid profiles, enhance endothelial function, optimize postprandial metabolism and cell membrane signaling, making it a functional model for human longevity. The PAF-Implicated Atherosclerosis Theory has emerged as a key unifying framework, proposing that Platelet-Activating Factor (PAF)—a highly potent lipid inflammatory mediator—plays a central role in the initiation and progression of atherosclerosis. Oxidized LDL promotes the production of PAF and PAF-like lipids, leading to endothelial dysfunction, vascular inflammation, and atherosclerotic plaque formation. Traditional Mediterranean foods are rich in natural PAF inhibitors, particularly the polar lipid fractions of extra virgin olive oil, as well as wine, fish, vegetables, onions, and garlic. Animal studies demonstrate that these compounds can reduce or even regress atherosclerotic lesions, independently of serum cholesterol levels. Human dietary interventions have further shown that MD-based meals and functional foods enriched with PAF inhibitors reduce PAF activity and improve thrombosis-related biomarkers. This mechanistic framework helps explain phenomena such as the “French Paradox” and the cardio-protective effects associated with fish consumption. Moreover, the extraction of PAF inhibitors from Mediterranean food by-products, such as olive pomace, offers promising ecological and economic advantages. Collectively, targeting PAF and increasing dietary intake of PAF inhibitors represent promising strategies for the prevention and management of atherosclerosis and other inflammatory diseases, supporting the view that PAF may function as a major, modifiable risk factor in these conditions. Full article

Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer glucose-lowering, cardio-protective and reno-protective properties. Mortality rates constitute a central endpoint for understanding the overall clinical value of SGLT2 inhibitors. This systematic review and meta-analysis aims to compare mortality outcomes associated with SGLT2 inhibitors across different populations. A systematic search was performed in four databases—PubMed, Scopus, Web of Science (WOS) and Cochrane CENTRAL—in March 2025. We strictly included randomized controlled trials (RCTs) that compared patients who received SGLT2is to control patients regarding mortality outcomes. All-cause mortality up to one year, all-cause mortality more than one year, cardiovascular mortality, renal mortality and in-hospital mortality were the extracted outcomes. Finally, RevMan (5.4) was adopted for meta-analysis, and OpenMeta analyst software was adopted for meta-regression. Fifty clinical trials met the eligibility criteria of the current systematic review and meta-analysis. SGLT2 inhibitors significantly reduced all-cause mortality in studies with follow-up of up to one year (RR = 0.89, 95% CI [0.80–0.99], p = 0.03). This early survival benefit was primarily driven by the subgroup of patients treated during acute cardiac decompensation (RR = 0.76, 95% CI [0.60–0.97], p = 0.03). Furthermore, long-term follow-up beyond one year showed a significant reduction in all-cause mortality (RR = 0.89, 95% CI [0.85–0.94], p < 0.0001), particularly among patients with chronic heart failure, chronic kidney disease (CKD), and diabetes mellitus (DM) with established cardiovascular disease (CVD) (following sensitivity analyses). Cardiovascular mortality was also significantly reduced overall (RR = 0.88, 95% CI [0.84–0.94], p < 0.0001), with the greatest benefit observed in chronic heart failure and CKD subgroups. SGLT2 inhibitors as a class provide a consistent and significant reduction in all-cause mortality across both short-term (up to one year) and long-term follow-up. The early survival benefit is particularly evident when initiated during acute cardiac decompensation, while the long-term benefit extends to chronic heart failure, CKD, and high-risk DM. Future well-designed trials are needed to address the impact of less-explored SGLT2 inhibitors and understudied populations. Full article

Atrial fibrillation (AF) frequently coexists with chronic kidney disease (CKD), and their combination confers a disproportionate risk of both thromboembolic and bleeding events. Conventional anticoagulation strategies rely primarily on creatinine clearance-based dosing, which reflects pharmacokinetic safety but does not fully capture the biological processes underlying thrombohemorrhagic instability. This narrative review synthesizes recent mechanistic and translational evidence regarding the bidirectional cardio–renal axis in AF and CKD, focusing on systemic inflammation, endothelial dysfunction, platelet dysregulation, and altered coagulation. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science (2018–2026) was performed, complemented by manual review of key references and guidelines. The evidence indicates that inflammatory cytokine activation, oxidative stress, glycocalyx degradation, von Willebrand factor dysregulation, uremic platelet dysfunction, and enhanced thrombin generation converge to create a disrupted vascular interface in which stroke and bleeding arise from shared pathophysiological mechanisms. Renal trajectory and selected circulating biomarkers further highlight the dynamic and heterogeneous nature of risk in advanced CKD. These findings support reframing anticoagulation decision-making in AF with CKD from a static filtration-based model toward a biology-informed approach that integrates renal dynamics, endothelial and platelet phenotype, and clinical context to better align thromboembolic protection with hemorrhagic safety. Full article

As populations around the world continue to age, promoting healthy ageing has become a key public health priority. Nutrition plays a vital role in maintaining physical and cognitive function later in life, and omega-3 polyunsaturated fatty acids (PUFA) are essential components of cell membranes and are known for their anti-inflammatory and cardio-protective effects. Chronic inflammation and oxidative stress are major contributors to age-related decline, and omega-3s help mitigate these processes by modulating immune responses and improving endothelial function. This systematic review aims to examine the potential of omega-3 fatty acids to reduce inflammatory markers and improve overall health. Moreover, it aims to present the most effective dietary interventions in dairy cows that increase PUFA content in milk. PubMed, Web of Science, Scopus, and the Cochrane Library databases were searched for relevant articles published up to November 2025. Evidence suggests that older adults who consume higher levels of PUFA tend to have better cardiovascular health, preserved cognitive function, and a lower risk of age-related diseases such as Alzheimer’s and arthritis, and reduce the risk of frailty and disability in later years. Dietary manipulation to enhance PUFA in bovine milk represents a promising strategy for improving human nutrition while potentially benefiting cow health. Full article