Search Results (1,543)

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is associated with significant renal complications, affecting disease progression and patient outcomes. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have emerged as a key therapeutic strategy, offering cardiovascular and renal benefits in these patients. However, interindividual variability in response to dapagliflozin underscores the role of pharmacogenetics in optimizing treatment efficacy. This study investigates the influence of genetic polymorphisms on renal outcomes in HFrEF patients treated with dapagliflozin, focusing on variations in genes such as SLC5A2, UMOD, KCNJ11, and ACE. Methods: This prospective, observational cohort study was conducted at the National Heart Institute, Cairo, Egypt, enrolling 200 patients with HFrEF. Genotyping of selected single nucleotide polymorphisms (SNPs) was performed using TaqMan™ assays. Renal function, including estimated glomerular filtration rate (eGFR), Kidney Injury Molecule-1 (KIM-1), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels, was assessed at baseline and after six months of dapagliflozin therapy. Results: Significant associations were found between genetic variants and renal outcomes. Patients with AA genotype of rs3813008 (SLC5A2) exhibited the greatest improvement in eGFR (+7.2 mL ± 6.5, p = 0.004) and reductions in KIM-1 (−0.13 pg/mL ± 0.49, p < 0.0001) and NGAL (−6.1 pg/mL ± 15.4, p < 0.0001). Similarly, rs12917707 (UMOD) TT genotypes showed improved renal function. However, rs5219 (KCNJ11) showed no significant impact on renal outcomes. Conclusions: Pharmacogenetic variations influenced renal response to dapagliflozin in HFrEF patients, particularly in SLC5A2 and UMOD genes. These findings highlighted the potential of personalized medicine in optimizing therapy for HFrEF patients with renal complications. Full article

Background/Objectives: Recent Japanese guidelines recommend using the average sodium-to-potassium (Na/K) ratio from casual urine samples to assess hypertension and cardiovascular risk, suggesting cutoffs of 2 (optimal) and 4 (feasible). We aimed to evaluate the proportion of Korean individuals who would be classified as having elevated Na/K ratios using these cutoffs, based on random urine Na/K measurements obtained from the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset. Methods: We analyzed 50,440 participants from the KNHANES 2016–2023 with available random urine Na and K results. Annual urinary Na/K ratios were calculated, and the prevalence of ratios ≥2 and ≥4 was assessed by age and sex using sampling weights. Results: The weighted median Na/K ratios were consistently lower than the weighted means, indicating skewed distributions. From 2016 to 2023, the weighted median and mean values increased from 2.3 and 2.7 to 2.8 and 3.3, respectively. The prevalence of a Na/K ratio ≥2 increased from 60.5% to 72.0%, and that of a ratio ≥4 increased from 16.9% to 28.3%. A U-shaped trend in Na/K ≥4 prevalence was observed by age, highest among those <20 and ≥70 years. Males had a higher prevalence than females in all age groups except 20–29. Conclusions: A growing proportion of Koreans exceeded Na/K cutoffs of 2 and 4 over time. Age- and sex-specific variation suggests tailored interpretation may be necessary when applying these thresholds in population health monitoring. Full article

Oxidative stress directly or indirectly contributes to the development and progression of various diseases; therefore, regulating oxidative stress is a promising strategy for preventing or treating these conditions. The unique substances in soybeans, soy isoflavones, notably genistein, which have a strong antioxidant capacity, are considered to regulate various signaling pathways, alleviate oxidative stress, and improve gut microbiota imbalance as well as mitochondrial dysfunction. In this literature review, we summarize the latest research on genistein, providing evidence of its development and application as a potential drug for preventing and treating five selected diseases (Parkinson’s disease, Alzheimer’s disease, diabetes mellitus, cardiovascular disease, and cancers). The literature was searched using keywords that include tripartite combinations of genistein and oxidative stress, along with each of the five selected diseases, from PubMed, Science Direct, and Google Scholar between 2014 and 2024. According to current in vitro, in vivo, and clinical trials, we comprehensively discuss the therapeutic dose used to target various disease entities to achieve optimal efficacy and meet safety requirements. Moreover, considering the poor water solubility and limited bioavailability of genistein, strategies for improving its therapeutic efficacy, such as combining it with exercise, existing medications, and advanced technologies, as well as applying nanotechnology, were assessed. Therefore, this review aims to provide robust evidence for the development and application of genistein as a potential therapeutic agent or functional food for preventing and treating these diseases. Full article

Non-pharmacological interventions, such as physical activity and exercise, are essential in managing type 1 diabetes mellitus by improving glycemic control, cardiovascular health and autonomic function. Given the chronic nature and long-term complications associated with type 1 diabetes, strategies beyond pharmacotherapy are essential. This review examines the effects of exercise on heart rate variability, a key indicator of autonomic nervous system activity. A systematic search was conducted in March 2024 across PubMed, Embase, Cochrane and CINAHL databases. Studies evaluating the retrospective or prospective impact of exercise or physical activity on heart rate variability parameters were included. Utilizing best evidence synthesis, the methodological quality of the included studies was evaluated. Seven studies met the inclusion criteria, all of which were rated as methodologically weak. Moderate evidence suggests that exercise may enhance heart rate variability, particularly by increasing parasympathetic activity and improving sympathovagal balance. However, evidence remains limited regarding the optimal type, frequency and intensity of exercise. Exercise appears to support autonomic function in individuals with type 1 diabetes mellitus. Nonetheless, further high-quality research is needed to determine the most effective exercise modalities and to inform evidence-based clinical guidelines. Full article

Background: Methylene blue (MB), a versatile redox agent, is emerging as a promising therapeutic in diseases associated with mitochondrial dysfunction. Its ability to optimize the electron transport chain increases ATP synthesis (30–40%) and reduces oxidative stress, protecting cellular components such as mitochondrial DNA. The protective role of this compound has been described in several neurodegenerative disease such as Alzheimer’s and Parkinson’s diseases. However, its role in cardiovascular disease has been poorly explored. Methods: In this study, we explored the impact of MB on murine (HL1) and human (AC16) cardiomyocyte redox signaling and cellular survival using RT-Qpcr analysis and immunochemistry assays. Results: Our results revealed that MB increased functional mitochondria, reversed H₂O₂-induced oxidative damage, and modulated antioxidant gene expression. Furthermore, it regulated the microRNA16–UPR signaling axis, reducing CHOP expression and promoting cell survival. Conclusions: These findings underscore its potential in cardioprotective therapy; however, its putative use as a drug requires in vivo validation in preclinical animal models. Full article

Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article

Background: Metabolic syndrome (MS) is a major public health concern linked to an elevated risk of type 2 diabetes and cardiovascular disease. Simple, reliable screening tools are needed for early identification, especially in working populations. Objective: To compare the diagnostic accuracy of body mass index (BMI), waist-to-height ratio (WtHR), triglyceride–glucose index (TyG), and waist–triglyceride index (WTI) for detecting MS based on NCEP ATP III and IDF criteria in a large cohort of Spanish workers. Methods: This cross-sectional study analyzed data from 386,924 Spanish workers. MS was diagnosed using NCEP ATP III and IDF definitions. The four indexes were evaluated by sex using a receiver operating characteristic (ROC) curve analysis. Area under the curve (AUC), optimal cut-off points, and Youden’s index were calculated. Results: TyG and WTI had the highest AUC values in men (0.911 and 0.901, respectively) for NCEP ATP III-defined MS, while WtHR and WTI achieved the best performance in women (0.955 and 0.953, respectively). WtHR outperformed BMI in all subgroups. Optimal cut-off values were identified according to sex and the definition of MS: TyG (8.95 men, 8.51 women), WtHR (0.54 men, 0.51 women), and WTI (170.6 men, 96.5 women), supporting their practical implementation in occupational health programs. All indexes showed significant discriminatory capacity (p < 0.001). Conclusions: TyG, WtHR, and WTI are more effective than BMI in detecting MS among Spanish workers, with sex-specific patterns. Their ease of use and diagnostic strength support their adoption in occupational health programs for early cardiometabolic risk detection. Full article

Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article

Vitexin and isovitexin are dietary flavonoids widely distributed in food and medicinal plants. They have attracted increasing attention owing to their diverse pharmacological activities and favorable safety profiles. These compounds exhibit therapeutic potential across multiple biological systems, including the immune, nervous, respiratory, cardiovascular, and endocrine systems, through antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms. Although previous reviews have addressed the pharmacological effects of vitexin and isovitexin, most are limited in scope—either focusing solely on vitexin or restricted to specific disease models such as cancer or diabetes. Moreover, some studies are outdated and do not reflect the recent advances in synthetic modification, green extraction technologies, and systems pharmacology. This review aims to provide a comprehensive evaluation of the pharmacological properties, pharmacokinetics, and clinical relevance of vitexin and isovitexin, highlighting their potential in disease prevention and treatment. A literature search was conducted using Web of Science, PubMed, and Google Scholar, with keywords including “vitexin”, “isovitexin”, “disease”, and “mechanism”. Here, we summarize the current research on the pharmacological effects of vitexin and isovitexin in metabolic disorders, inflammatory diseases, cancer, and neurodegenerative conditions, focusing on their molecular mechanisms and therapeutic targets. Furthermore, we discussed their toxicity, bioavailability, pharmacokinetics, and clinical research findings. Vitexin and isovitexin hold promise as therapeutic agents or adjuncts for multiple diseases with potential applications in modern medicine and healthcare. However, their pharmacological mechanisms, clinical efficacy, and potential synergistic effects with other therapeutic agents remain unclear. Further systematic research is needed to clarify molecular targets and optimize their therapeutic applications. Full article

Background: Venous thromboembolism (VTE) is conventionally treated with anticoagulant therapy. In contrast, the core treatment for peripheral artery disease (PAD) is antiplatelet therapy. VTE and PAD share common risk factors and may occur in the same patient. Nonetheless, there is little evidence of the best antithrombotic regimen to use when the two conditions coexist, especially in terms of the extended prevention of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and VTE recurrences. Methods: We conducted an online survey of members of the Italian Society of Angiology and Vascular Medicine (SIAPAV) to explore current prescribing habits for extended antithrombotic therapy in patients with PAD and unprovoked VTE. The survey included four clinical scenarios with variations in age, gender, bleeding risk, index VTE event, and severity of PAD. In all cases, patients had received anticoagulation for 6 months, and the key question was how to continue treatment beyond 6 months from the index VTE event. Results: A total of 174 clinicians participated to the survey. The most common choice was combining antiplatelet therapy with a direct oral anticoagulant (DOAC) at a low dose. Full-dose DOAC alone or antiplatelet therapy alone were less frequently chosen. Older age and high bleeding risk increased the preference for antiplatelet therapy alone. Conclusions: This survey highlights the marked variability in antithrombotic prescribing patterns among specialists in vascular medicine for patients with unprovoked VTE and concomitant PAD, reflecting the lack of evidence on optimal management in this specific setting. More research is needed to define the safest and most effective treatment strategies for patients with concurrent PAD and VTE. Full article

Menopause is characterized by a decline in estrogen levels, leading to symptoms such as vasomotor instability, osteoporosis, and increased cardiovascular and cognitive risk. Hormone replacement therapy (HRT) remains the gold standard for managing menopausal symptoms; however, concerns regarding its long-term safety, including elevated risks of cancer and cardiovascular events, have prompted interest in alternative therapies. Phytoestrogens, particularly the isoflavones daidzein and genistein, are plant-derived compounds structurally similar to 17β-estradiol (E2) and capable of binding estrogen receptors. Found abundantly in soybeans and red clover, these compounds exhibit selective estrogen receptor modulator (SERM)-like activity, favoring ERβ over ERα, which underlies their tissue-specific effects. In vitro, in silico, and in vivo studies demonstrate their ability to modulate estrogenic pathways, inhibit oxidative stress, and influence reproductive and neurological function. Clinical trials show that daidzein and genistein, especially in equol-producing individuals, can reduce vasomotor symptoms such as hot flashes and night sweats. While results across studies vary, consistent findings support their safety and modest efficacy, particularly for women unable or unwilling to use HRT. Pharmacokinetic studies reveal moderate bioavailability and interindividual variability due to gut microbiota metabolism. At dietary levels, these compounds are generally safe, although high-dose supplementation is discouraged in individuals with hormone-sensitive cancers. Emerging evidence suggests lifelong consumption of soy-based foods may reduce cancer risk. In conclusion, daidzein and genistein represent promising, well-tolerated natural alternatives to conventional HRT, offering symptom relief and additional health benefits. Further research is warranted to optimize dosing, improve clinical outcomes, and clarify long-term safety in diverse populations, particularly with genetic variations in isoflavone metabolism. Full article

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article

Background and Objectives: The perioperative use of beta-blockers remains controversial due to conflicting evidence of their risks and benefits. The aim of this study was to evaluate the association between chronic beta-blocker (bb) therapy and perioperative cardiac events in non-cardiac surgeries using 24 h continuous Holter monitoring. Materials and Methods: A prospective observational study was conducted on patients undergoing elective or emergency non-cardiac surgery at a Romanian tertiary care hospital. The patients were divided into two groups: G1 (not receiving Bb) and G2 (on chronic Bb). The incidences of perioperative cardiac events, such as severe bradycardia (<40 b/min), new-onset atrial fibrillation (AF), extrasystolic arrhythmia (Ex), and sustained ventricular tachycardia (sVT) and arterial hypotension, were compared between the two groups using clinical, electrocardiography (ECG), and Holter ECG data. Beta-blocker indications, complications, and outcomes were analyzed using chi-squared tests and logistic regression. Results: A total of 100 consecutive patients (63% men, mean age of 53.7 years) were enrolled in the study. G2 included 30% (n = 30) of patients on chronic beta-blocker therapy. The indications included atrial fibrillation (46.7%, n = 14), arterial hypertension (36.7%, n = 11), extrasystolic arrhythmias (10%, n = 3), and chronic coronary syndrome (6.6%, n = 2). Beta-blocker use was significantly associated with severe bradycardia (n = 6; p < 0.001) in G2, whereas one patient in G1 had bradycardia, and 15 and 1 patients had hypotension (p < 0.001) in G1 and G2, respectively. The bradycardia and arterial hypotension cases were promptly treated and did not influence the patients’ prognoses. The 14 patients with AF in G2 had a 15-fold higher odds of requiring beta-blockers (p < 0.001, odds ratio (OR) = 15.145). No significant associations were found between beta-blocker use and the surgery duration (p = 0.155) or sustained ventricular tachycardia (p = 0.857). Ten patients developed paroxysmal postoperative atrial fibrillation (AF), which was related to longer surgery durations (165 (150–180) vs. 120 (90–150) minutes; p = 0.002) and postoperative anemia [hemoglobin (Hg): 10.4 (9.37–12.6) vs. 12.1 (11–13.2) g/dL; p = 0.041]. Conclusions: Patients under chronic beta-blocker therapy undergoing non-cardiac surgery have a higher risk of perioperative bradycardia and hypotension. Continuous Holter monitoring proved effective in detecting transient arrhythmic events, emphasizing the need for careful perioperative surveillance of these patients, especially the elderly, in order to prevent cardiovascular complications These findings emphasize the necessity of tailored perioperative beta-blocker strategies and support further large-scale investigations to optimize risk stratification and management protocols. Full article

Aging is a multifaceted biological process characterized by a progressive decline in cellular function and physiological resilience, increasing the risk of multiple chronic conditions. Chronic lung diseases frequently manifest within the aging population and are closely intertwined with systemic dysfunctions across cardiovascular, musculoskeletal, and neurological systems. In this review, we explore the biological mechanisms linking aging, multiple chronic conditions patterns, and chronic lung disease, with a particular focus on inflammaging and cellular aging. We also highlight shared pathological pathways such as oxidative stress, mitochondrial dysfunction, and the dysregulation of repair processes that underlie both natural aging and the accelerated aging seen in chronic lung disease. Additionally, we discuss the systemic impact of multiple chronic conditions on patient outcomes, including increased frailty, diminished physical capacity, cognitive impairment, and elevated mortality risk. This review advocates for a comprehensive, patient-centered approach that combines early detection, personalized pharmacological therapies targeting inflammatory and senescent pathways, and non-pharmacological interventions such as pulmonary rehabilitation, exercise, and dietary optimization. Emerging therapeutics, including senolytics and anti-inflammatory agents, present promising avenues for mitigating age-related lung decline and managing multiple chronic conditions. Full article

This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of Science databases, covering studies from 1981 to 2025. It was revealed that over 94% of records in Scopus and Web of Science are duplicated in PubMed, so the latter was used for the search in our study. After duplicate removal and independent screening, 89 from 1123 retrieved studies were selected for the search. The analysis revealed a broad spectrum of diclofenac’s non-traditional pharmacological activities, including neuroprotective, antiamyloid, anticancer, antiviral, immunomodulatory, antibacterial, antifungal, anticonvulsant, radioprotective, and antioxidant properties, primarily identified through preclinical In vitro and In vivo studies. These effects are mediated through diverse molecular pathways beyond cyclooxygenase inhibition, such as modulation of neurotransmitter release, apoptosis, and cellular proliferation. Diclofenac showed potential for repositioning in oncology, neurodegenerative disorders, infectious diseases, and immune-mediated conditions. Its hepatotoxicity and cardiovascular risks necessitate strategies like advanced drug formulations, dose optimization, and personalized medicine to enhance safety. Large-scale randomized clinical trials are essential to validate these findings and ensure safe therapeutic expansion. Full article