Search Results (7,511)

Recent advances in single-cell RNA sequencing (scRNA-seq) have substantially deepened our understanding of adult hippocampal neurogenesis (AHN), enabling the detection of neural stem cells, progenitors, and immature neurons in postmortem human brain tissue and revealing how these populations are altered in neurological disease. Additionally, scRNA-seq enables the identification of disease-specific cell subtypes and distinct gene expression signatures associated with neurological disorders, many of which are linked to alterations in AHN and cognitive function. Such cellular- and molecular-level insights into neurological disease mechanisms provide a strong foundation for the development of targeted therapeutic strategies. Indeed, scRNA-seq has also emerged as a powerful tool in drug discovery and development across multiple disease areas, including cancer, cardiovascular disorders, and neurological conditions. In this review, we offer a comprehensive and integrative perspective on the cellular and molecular landscape of human hippocampal neurogenesis, the pathological mechanisms underlying neurological disorders, and their implications for therapeutic development. Full article

Hypertension (HTN) remains a leading modifiable risk factor for cardiovascular disease, and non-pharmacological strategies combining exercise training with plant-derived bioactive supplementation are increasingly recognized as promising adjuncts for blood pressure (BP) management. This evidence-based review synthesizes findings from 31 clinical studies investigating selected plant-based supplements with the strongest available clinical evidence, namely beetroot juice (BRJ), green tea (GT), curcumin (CN), resveratrol (RSV), and garlic, administered alone or in combination with different exercise modalities across acute, short-term, and long-term interventions. Collectively, the evidence indicates that BRJ exerts the most consistent BP-lowering effects, particularly during aerobic training performed at ~50% heart rate reserve (HRR), or ~60% peak oxygen consumption (VO_2peak) in individuals with early-stage vascular dysfunction. CN and garlic also enhance exercise-induced BP reductions, especially in older or metabolically compromised populations. GT shows variable outcomes depending on caffeine content, exercise modality, and participant health status, while RSV provides modest vascular support, often contingent on concurrent training. Mechanistically, these botanicals and exercise converge on key vascular-regulatory pathways, including enhanced nitric oxide (NO) bioavailability, reduced oxidative stress and inflammation, attenuated renin–angiotensin–aldosterone system (RAAS) and sympathetic activity, and improved mitochondrial function through Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signaling. Together, these integrated mechanisms improve endothelial function, lower vascular resistance, and ultimately reduce BP. From a translational standpoint, combining exercise with targeted plant-based supplementation offers a safe, accessible, and physiologically synergistic strategy for BP control in clinical populations. Future research should define optimal dosing, timing relative to exercise, and population-specific efficacy to inform precision-based, integrative interventions for HTN management. Full article

Background and Objectives: Diabetes mellitus (DM) has been consistently linked to severe coronavirus disease 2019 (COVID-19) and adverse outcomes; however, the extent to which DM independently predicts mortality and cardiovascular complications in real-world hospitalized cohorts remains debated, particularly in Eastern Europe. This study aimed to evaluate the impact of DM on cardiovascular complications and in-hospital outcomes among adults hospitalized with SARS-CoV-2 infection. Materials and Methods: We conducted a single-center retrospective observational cohort study including consecutive adult patients hospitalized with laboratory-confirmed SARS-CoV-2 infection between March 2020 and December 2024 at the “Victor Babeș” Clinical Hospital of Infectious Diseases and Pneumophthisiology, Timișoara, Romania. DM status (type 1, type 2, or newly diagnosed diabetes) was defined using structured dataset fields. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included ICU admission, length of stay, pulmonary embolism (PE) on CT pulmonary angiography (CTPA), and a composite of in-hospital cardiovascular/thromboembolic complications. Multivariable logistic regression models adjusted for clinically relevant covariates (age, sex, BMI, vaccination status, hypertension, ischemic heart disease, atrial fibrillation, prior ischemic stroke, and admission creatinine). Results: A total of 395 patients were included; 98 (24.8%) had DM. Diabetic patients exhibited a high cardiometabolic burden (arterial hypertension: 83.7% vs. 77.4%, p = 0.242) and higher admission renal markers (urea: 55.6 [41.0–79.1] vs. 48.6 [39.2–68.0] mg/dL, p = 0.047; creatinine: 1.04 [0.76–1.52] vs. 0.88 [0.59–1.33] mg/dL, p = 0.008). In-hospital mortality was numerically higher in DM (9.2% vs. 6.7%, p = 0.560), as was ICU admission (7.1% vs. 4.7%, p = 0.503), without statistical significance. PE on CTPA occurred in 13.3% of DM vs. 11.4% of non-DM patients (p = 0.763). In univariable analysis, DM was not significantly associated with mortality (OR 1.40, 95% CI 0.62–3.19; p = 0.422) or ICU admission (OR 1.55, 95% CI 0.61–3.97; p = 0.356). After multivariable adjustment, DM remained not independently associated with mortality (adjusted OR 1.09, 95% CI 0.42–2.83; p = 0.854) or ICU admission (adjusted OR 1.19, 95% CI 0.42–3.36; p = 0.747). Conclusions: In this real-world Eastern European cohort of hospitalized adults with SARS-CoV-2 infection, diabetes mellitus was common and associated with significantly worse renal function at admission, but it was not statistically associated with in-hospital mortality or ICU admission after multivariable adjustment; however, the limited number of events and low events-per-variable raise concerns about model stability and potential false-negative findings. These findings support a risk-marker model in which adverse COVID-19 outcomes in diabetic patients are driven primarily by clustered vulnerability and organ dysfunction rather than diabetes status alone. Full article

Background: Cardiorenometabolic syndrome (CRMS) reflects the interaction between heart failure (HF), chronic kidney disease, and metabolic disorders. Its prognostic impact during the acute phase of HF remains poorly defined. The primary objective of this study was to assess whether severe CRMS (sCRMS: estimated glomerular filtration rate <45 mL/min/1.73 m² associated with type 2 diabetes mellitus and/or obesity) predicts worse clinical outcomes. Methods: This was a retrospective observational study of a prospective cohort including 2228 patients admitted for acute HF between 2015 and 2025. Clinical characteristics and outcomes (mortality, HF readmission, and the composite endpoint) were compared between patients with and without sCRMS. Results: sCRMS was present in 486 patients (21.8%) who were older, had worse functional class, and a higher burden of cardiovascular comorbidities. They presented more frequently with systemic congestion and less often with de novo HF. During follow-up, sCRMS was associated with higher mortality (29.4% vs. 18.4%), HF readmissions (56.2% vs. 33.5%), and the composite endpoint (85.6% vs. 51.9%) (all p < 0.001). In multivariable analysis, sCRMS remained an independent predictor of mortality (HR 1.25), readmissions (HR 1.24), and overall morbidity and mortality (HR 1.20). Conclusions: In patients hospitalized for acute HF, sCRMS consistently identified a clinically vulnerable phenotype with an unfavorable prognosis. These findings support the value of sCRMS as a simple and reproducible prognostic marker and highlight the need for integrated cardiorenometabolic strategies during post-discharge follow-up. Full article

Mitochondria are central regulators of cardiac homeostasis, integrating energy production, redox balance, calcium handling, and innate immune signaling. In cardiovascular disease (CVD), mitochondrial dysfunction acts as a unifying mechanism connecting oxidative stress, metabolic inflexibility, inflammation, and structural remodeling. Disturbances in mitochondrial quality control—encompassing fusion–fission dynamics, PINK1/Parkin- and receptor-mediated mitophagy, biogenesis, and proteostasis—compromise mitochondrial integrity and amplify cardiomyocyte injury. Excess reactive oxygen species, mitochondrial DNA release, and calcium overload further activate cGAS–STING, NLRP3 inflammasomes, and mPTP-driven cell death pathways, perpetuating maladaptive remodeling. Therapeutic strategies targeting mitochondrial dysfunction have rapidly expanded, ranging from mitochondria-targeted antioxidants (such as MitoQ and SS-31), nutraceuticals, metabolic modulators (SGLT2 inhibitors, metformin), and mitophagy or biogenesis activators to innovative approaches including mtDNA editing, nanocarrier-based delivery, and mitochondrial transplantation. These interventions aim to restore organelle structure, improve bioenergetics, and reestablish balanced quality control networks. This review integrates recent mechanistic insights with emerging translational evidence, outlining how mitochondria function as bioenergetic and inflammatory hubs in CVD. By synthesizing established and next-generation therapeutic strategies, it highlights the potential of precision mitochondrial medicine to reshape the future management of cardiovascular disease. Full article

The close physiological relationship between the left atrium (LA) and left ventricle (LV) suggests that an index assessing both the cardiac chambers simultaneously could provide useful information about disease severity. Consequently, investigators have proposed the atrioventricular coupling index (LACi) and demonstrated its utility in predicting the likelihood of atrial fibrillation, heart failure, and other cardiovascular events in humans. No studies have been reported in veterinary medicine. Therefore, we measured the LACi in healthy dogs and dogs affected by myxomatous mitral valve disease (MMVD). Two hundred and thirty-three dogs (105 healthy dogs and 128 dogs with MMVD) were retrospectively included in the study. The LACi (LA volume/LV volume × 100) at LV end-diastole (LACi-ED) and LV end-systole (LACi-ES) of each dog was measured using a monoplane Simpson’s Method of Discs from the left apical four-chamber view. In healthy dogs, LACi-ED and LACi-ES showed no relationship with bodyweight, heart rate and age (R² < 0.03, for all variables). In MMVD dogs, LACi-ED and LACi-ES differed between ACVIM stages (p < 0.001 and p < 0.02, for all stages). The LACi-ED and LACi-ES had similar accuracy in identifying MMVD dogs with congestive heart failure (area under the curve of 0.920 and 0.906, respectively). Our data suggest that the LACi can be useful in assessing left atrioventricular function in dogs with MMVD but the diagnostic accuracy in identifying dogs with congestive heart failure was not superior to the left atrial-to-aortic ratio. Prospective studies are needed to evaluate the predictive value of this new echocardiographic index in dogs affected by MMVD. Full article

Functional foods have attracted increasing scientific and commercial interest due to their potential roles in health promotion and the prevention of non-communicable diseases such as diabetes and cardiovascular diseases. In this review, we will critically examine the current evidence on functional foods by focusing on their classification, bioactive components, biological mechanisms, consumer acceptance and regulatory frameworks. Bioactive compounds, such as polyphenols, dietary fibre and probiotics, from both plant- and animal-origin functional foods, have also been examined in this review. Despite substantial experimental and epidemiological evidence, the translation of functional foods into consistent health benefits remains challenged by variability in bioavailability, food matrix effects, processing conditions and interindividual differences in genetics and gut microbiota. Key mechanistic determinants of bioefficacy, including intestinal transport processes, molecular structure, stereochemistry, and food–drug interactions, are discussed. Consumers’ perception and purchasing behaviour are examined, identifying the influence of product format, socio-demographic characteristics, information sources, health motivation and price sensitivity. Our review also compares the regulatory approaches in the United States, European Union, Japan and China, highlighting the heterogeneity in definitions and health claim substantiation requirements. Finally, emerging opportunities such as metabolic profiling technologies and personalised nutrition are highlighted as future directions to support evidence-based, effective and equitable functional food development. Full article

Cardiovascular disease and diabetes mellitus have now reached pandemic proportions, and their association has become very common. Some patients with coronary artery disease and diabetes remain symptomatic, with chest pain present despite the implementation of evidence-based medical treatment and maximal therapy. A hypothesis increasingly confirmed in clinical practice is that epicardial or microvascular spasm, or both, are frequently responsible for the lack of symptom control or for the occurrence of major adverse cardiovascular events. Our review provides the most up-to-date and in-depth analysis of the available literature to provide solid knowledge about coronary spasm in diabetes patients. We have deepened the substrate of coronary spasm in relation to the multiple and complex structural and functional abnormalities produced by chronic hyperglycemia, with the ultimate goal of allowing optimization of treatment and improving patient outcomes. Full article

Background: The number of patients with chronic coronary syndromes (CCS) is growing, influenced by factors such as increasing life expectancy and prevalence of risk factors. Thus, cardiovascular (CV) disease remains the leading cause of mortality and morbidity worldwide. The main objective of the study was to identify factors associated with long-term survival in patients with chronic coronary syndrome, with a focus on kidney function described by eGFR and albuminuria (assessed by uACR). Methods: The study comprised a total of 257 patients from Bialystok (Poland), aged ≤ 80 years, who 6–18 months earlier were hospitalized for acute coronary syndrome or elective myocardial revascularization. During the 80-month follow-up, 40 (15.6%) patients died, while there was no information about three (1.2%) patients. Patients with preserved eGFR and without albuminuria were characterized by the longest survival, with deterioration of prognosis in groups of progressive kidney dysfunction as defined by KDIGO based on eGFR and uACR. The primary endpoint was death from any cause. Results: Those who survived the 80-month follow-up period were younger (p < 0.001), had a lower waist circumference (p = 0.028), higher diastolic blood pressure (p = 0.026), lower NTproBNP (p < 0.001) and hsCRP (p = 0.001) concentrations, reduced eGFR (p = 0.004) and increased ACR (p = 0.023) were strongly associated with mortality. In logistic regression analysis with stepwise elimination of variables, the strongest factors affecting survival were hemoglobin concentration, left ventricle ejection fraction (LVEF) and hsCRP. Conclusions: Measurement of albuminuria, in addition to eGFR, allows patients to be correctly classified into CV risk categories and facilitates appropriate treatment of patients with CCS. Higher diastolic blood pressure (but still within normal range) was found in patients who later survived 6 years. Measurements of hsCRP, hemoglobin concentration and LVEF help to identify CCS patients at the highest risk of mortality in long-term follow-up. Full article

Background: Atherosclerotic cardiovascular disease (ASCVD) frequently coexists with type 2 diabetes (T2D), amplifying morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RA) confer significant cardiovascular benefits and are recommended for patients with T2D and established ASCVD. However, real-world use may not reflect a complication-driven therapeutic approach. Methods: This retrospective study included adults with T2D and established ASCVD (prior myocardial infarction, ischemic stroke, transient ischemic attack, or symptomatic peripheral arterial disease) consecutively admitted to the internal medicine and cardiology departments of a tertiary hospital over a 60-day period. Pre-admission medication use, comorbidities, and laboratory parameters were recorded. Factors associated with GLP-1 RA use were assessed using logistic regression before and after 1:1 propensity score (PS) matching. Results: Among 202 eligible patients, 49 (24.3%) were treated with a GLP-1RA. GLP-1RA users were younger (71.9 vs. 77.8 years, p < 0.001), had lower hypertension prevalence (61.2% vs. 78.4%, p = 0.02), and were more frequently on insulin (69.4% vs. 25.5%, p < 0.001) and sodium-glucose cotransporter 2 inhibitors (55.1% vs. 28.1%, p = 0.001). After PS matching (48 pairs), demographic and comorbidity differences were attenuated, although insulin remained strongly associated with GLP-1RA therapy (Odds Ratio 11.85, p < 0.001). Neither cardiovascular disease burden—captured through the presence of multiple cardiovascular comorbidities—nor renal function were independently associated with GLP-1RA use after adjustment. Conclusions: In patients with T2D and established ASCVD, GLP-1RA use was more strongly associated with the intensity of glucose-lowering therapy—particularly insulin use—than with cardiovascular or renal risk profiles. These findings should be interpreted with caution given the retrospective observational design and the limited availability of glycated hemoglobin, anthropometry and diabetes duration data. However, they suggest that, in real-world clinical practice, GLP-1RA prescribing may remain predominantly glucose-centric rather than complication-driven, underscoring the need for improved implementation of contemporary diabetes guidelines. Full article

Obesity is a complex metabolic disorder characterized by excessive accumulation of adipose tissue, resulting from an imbalance between energy intake and expenditure. It is associated with an increased risk of chronic diseases such as type 2 diabetes, cardiovascular disease, and cancer. Kefiran is a water-soluble exopolysaccharide produced by lactic acid bacteria, Lactobacillus kefiranofaciens, in kefir grains, composed primarily of glucose and galactose. It has garnered scientific interest due to its antioxidant, anti-inflammatory, and antimicrobial properties. Rice Kefiran (RK) is a functional food made with culturing L. kefiranofaciens in a medium containing rice. It is standardized to contain at least 5 mg/g of kefiran. This study investigated the anti-obesity effect of RK on a high-fat diet (HFD)-induced obese mouse model. HFD-fed mice exhibited marked increases in body weight gain (10.3 g vs. 2.0 g in controls) and adipose tissue mass (2.4 g vs. 0.4 g in controls). RK administration significantly attenuated weight gain to 8.3 g and 6.0 g at doses of 10 and 50 mg/kg, respectively, and reduced adipose tissue mass to 2.2 g (RK10) and 1.7 g (RK50). Oral glucose tolerance testing revealed impaired glucose clearance in HFD-fed mice, with blood glucose levels of 403.5 mg/dL at 15 min and 314.6 mg/dL at 120 min, compared with 348.8 mg/dL and 232.2 mg/dL in controls. RK treatment improved glucose tolerance, particularly at 50 mg/kg, reducing glucose levels to 359.0 mg/dL at 15 min and 263.8 mg/dL at 120 min. Biochemical analyses demonstrated that RK significantly reduced serum total cholesterol (213.6 mg/dL in HFD vs. 178.0 and 184.0 mg/dL in RK10 and RK50), triglycerides (379.0 mg/dL in HFD vs. 228.8 and 234.6 mg/dL), and non-esterified fatty acids (0.89 mEq/mL in HFD vs. 0.54 and 0.35 mEq/mL), while phospholipid levels remained unchanged. Furthermore, RK increased serum nicotinamide phosphoribosyltransferase (NAMPT) levels from 15.8 ng/mL in HFD-fed mice to 30.0 and 50.0 ng/mL in the RK10 and RK50 groups, respectively, and restored hepatic NAD⁺/NADH ratios toward control levels (1.78 µmol/L in HFD vs. 1.90 µmol/L and 2.07 µmol/L in RK10 and RK50). Gene expression analysis showed that RK increased Nampt mRNA expression and decreased the mRNA expression of adipogenic and lipogenic genes, including Srebp-1c, Acc-1, and Fas. These findings suggest that RK may ameliorate obesity-related metabolic disturbances and its associated metabolic dysfunctions by modulating lipid metabolism, glucose tolerance, and NAD⁺ biosynthesis pathways. Full article

Vascular inflammation and endothelial dysfunction are key drivers in the development of cardiovascular and neurovascular diseases. Mitochondrial dysfunction and oxidative stress further amplify inflammatory cascades, emphasising the need for targeted strategies that restore endothelial homeostasis at the subcellular level. Hydrogen sulphide (H₂S) donors, such as AP39, offer cytoprotective benefits but are limited by short half-life and rapid release of the active compound, H₂S. We developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating AP39 (PLGA-AP39) to achieve sustained, mitochondria-targeted H₂S delivery. Nanoparticles were characterised by size, polydispersity, zeta potential, encapsulation efficiency, and in vitro release kinetics. Human umbilical vein endothelial cells (HUVEC) were exposed to TNF-α to induce inflammation, followed by treatment with free AP39 or PLGA-AP39. Anti-inflammatory effects were assessed by measuring IL-6, IL-8, and TGF-β levels. Mitochondrial function was evaluated using a Seahorse XFe24 Analyser, membrane potential assays, and mitochondrial ROS detection. Moreover, we investigated vascular function by analysing capillary-like tube formation and wound closure in response to treatments. PLGA-AP39 nanoparticles displayed a uniform size (~227 nm), low PDI, and high encapsulation efficiency (>78%). Sustained AP39 release was observed over seven days. Treatment with PLGA-AP39 significantly restored TNF-α-induced endothelial dysfunction and reduced TNF-α-induced release of IL-6, IL-8, and TGF-β compared to untreated controls. Seahorse analysis revealed restoration of maximal respiration and increased spare respiratory capacity. Encapsulated AP39 also preserved mitochondrial membrane potential and reduced mitochondrial ROS production, demonstrating enhanced protection against inflammation-induced metabolic dysfunction. This work establishes a novel nanoparticle-based strategy for prolonged, mitochondria-specific H₂S delivery to counteract vascular inflammation and enhance endothelial bioenergetics. The results from this work are pioneering in the generation of a novel delivery method for H₂S donors employing PLGA and represent a promising therapeutic avenue for treating chronic vascular inflammatory disorders. Full article

Background: Heart failure (HF) has a complex pathogenesis involving oxidative stress, inflammation, and energy metabolism disorders, and requires multi-target agents. Berberis kaschgarica Rupr. (BKR) is used in Uyghur folk medicine to improve cardiovascular health, but its cardioprotective mechanisms against HF remain unclear. Methods: UPLC-MS/MS was used to identify BKRE components; DPPH/ABTS assays evaluated antioxidant activity. The MTC of BKRE was determined in zebrafish, and its effects on ISO-induced HF zebrafish were assessed via cardiac function, apoptosis, oxidative stress, and inflammation indicators. Network pharmacology, molecular docking, transcriptomics, and qRT-PCR clarified targets and pathways. Results: BKRE contained 14 bioactive flavonoids/alkaloids with favorable drug-likeness, showing concentration-dependent DPPH and ABTS scavenging. In HF zebrafish, BKRE (5/10/20 μg/mL) dose-dependently improved cardiac function, inhibited apoptosis, reduced ROS and TNF-α/IL-6, restored GSH/T-SOD, activated the AMPK-PPARα-PGC-1α pathway by binding ALOX5/NQO1, etc. Conclusions: BKRE exerts multi-mechanistic cardioprotective effects, validating BKR’s ethnopharmacological value and highlighting it as a promising HF agent/functional food. Full article

Cardiovascular diseases and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing sharply worldwide and share overlapping pathophysiological pathways, including oxidative stress, inflammation, hyperglycemia, obesity, dyslipidemia, and hypertension. Dark chocolate, rich in cocoa flavanols such as epicatechin and catechin, exhibits antioxidant and anti-inflammatory effects. Based on these properties, this narrative review uniquely integrates evidence on chocolate’s effects on both cardiovascular and hepatic health, exploring shared mechanisms and clinical implications. Evidence from clinical studies suggests that chocolate modulates nitric oxide bioavailability and NADPH oxidase activity. Clinical findings demonstrate improvements in flow-mediated dilation, decreased NT-proBNP, reduced intestinal permeability and endotoxemia, improved lipid profile (increased HDL-c and reduced total cholesterol, LDL-c, and triglycerides), increased plasma polyphenols, improved platelet function, and attenuated hepatocyte apoptosis. These findings suggest a potential role for cocoa flavanol-rich dark chocolate in cardiometabolic health; however, the evidence remains preliminary and is limited by heterogeneous study designs, small sample sizes, and short intervention durations. Despite these limitations, current evidence supports the inclusion of moderate dark chocolate consumption as a possible adjunct strategy to mitigate cardiometabolic and hepatic metabolic risks. Further large-scale, long-term trials are needed to confirm these beneficial effects and to standardize the dosage and formulation of cocoa flavanols. Full article

Degenerative diseases are characterized by the gradual loss of cellular integrity, tissue function, and regenerative capacity. Cardiovascular diseases, neurodegenerative disorders, and musculoskeletal deterioration are considered major categories of degenerative diseases, and vitamin D deficiency has been linked with an increased risk of these conditions. Vitamin D has the potential to modulate neurogenerative process by influencing the progression of neuronal survival, neurogenesis, and synaptic plasticity through both genomic and non-genomic mechanisms mediated by vitamin D receptors, which are widely distributed across brain regions and cell types. Additionally, vitamin D regulates brain immunometabolism by modulating microglial and astrocytic inflammatory responses and oxidative stress. Vitamin D has long been recognized as essential for bone health. Beyond its classical role, vitamin D contributes to the maintenance of bone–muscle homeostasis, enhances mitochondrial biogenesis and ATP production while reducing oxidative stress, and facilitates bidirectional bone–muscle crosstalk through myokines and osteokines to coordinate bone remodeling and muscle regeneration. However, despite these mechanistic insights, the beneficial effects of vitamin D on these diseases—such as reduced risk or mitigation of progression—remains inconclusive. This review explores the relationships between vitamin D and cardiovascular, neurodegenerative, and musculoskeletal diseases, with a focus on the underlying immunological and metabolic mechanisms of actions. Full article