Search Results (12,578)

In the original randomised Dietary Intervention to Stop Coronary Atherosclerosis (DISCO-CT) trial, a 12-month Dietary Approaches to Stop Hypertension (DASH) project led by dietitians improved cardiovascular and metabolic risk factors and reduced platelet chemokine levels in patients with coronary artery disease (CAD). It is unclear whether these benefits are sustained. Objective: To determine whether the metabolic, inflammatory, and clinical benefits achieved during the DISCO-CT trial are sustained six years after the structured intervention ended. Methods: Ninety-seven adults with non-obstructive CAD confirmed in coronary computed tomography angiography were randomly assigned to receive optimal medical therapy (control group, n = 41) or the same therapy combined with intensive DASH counselling (DASH group, n = 43). After 301 ± 22 weeks, 84 individuals (87%) who had given consent underwent reassessment of body composition, meal frequency assessment, and biochemical testing (lipids, hs-CRP, CXCL4, RANTES and homocysteine). Major adverse cardiovascular events (MACE) were assessed. Results: During the intervention, the DASH group lost an average of 3.6 ± 4.2 kg and reduced their total body fat by an average of 4.2 ± 4.8 kg, compared to an average loss of 1.1 ± 2.9 kg and a reduction in total body fat of 0.3 ± 4.1 kg in the control group (both p < 0.01). Six years later, most of the lost body weight and fat tissue had been regained, and there was a sharp increase in visceral fat area in both groups (p < 0.0001). CXCL4 decreased by 4.3 ± 3.0 ng/mL during the intervention and remained lower than baseline values; in contrast, in the control group, it initially increased and then decreased (p < 0.001 between groups). LDL cholesterol and hs-CRP levels returned to baseline in both groups but remained below baseline in the DASH group. There was one case of MACE in the DASH group, compared with four cases (including one fatal myocardial infarction) in the control group (p = 0.575). Overall adherence to the DASH project increased by 26 points during counselling and then decreased by only four points, remaining higher than in the control group. Conclusions: A one-year DASH project supported by a physician and dietitian resulted in long-term suppression of the proatherogenic chemokine CXCL4 and fewer MACE over six years, despite a decline in adherence and loss of most anthropometric and lipid benefits. It appears that sustained systemic reinforcement of behaviours is necessary to maintain the benefits of lifestyle intervention in CAD. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article

Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice. Full article

Medium-chain fatty acid triglycerides (MCTs) possess antibacterial, antiviral, nutritional, and other biological activities and have demonstrated significant application potential in humans and terrestrial animals. In recent years, with the development of the green aquaculture industry, MCTs have been gradually applied to aquaculture animals, which can enhance growth performance, improve flesh quality, regulate lipid metabolism, boost immune activity, and modulate the intestinal flora, thereby improving the production efficiency of aquaculture. This paper elaborates in detail on the biological activities of MCTs and their applications in aquatic animals, providing a theoretical and practical basis for the application of MCTs in aquaculture. Full article

Blood flow restriction training (BFRT) offers notable advantages, including simplicity and time efficiency. However, no meta-analysis has yet comprehensively evaluated its effects on glucose and lipid metabolism in overweight or obese adults. This meta-analysis examines the potential efficacy of BFRT in improving glycemic and lipid control in overweight/obese adults. The literature was searched in six databases, with the search period up to 31 March 2025. A total of eight randomized controlled trials involving 267 participants were identified. Data were analyzed using Stata 18.0 and RevMan 5.4 with random effects models. Outcomes included fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles, and risk of bias and publication bias (Egger’s test) were assessed. BFRT significantly reduced FBG (Hedges’ g = −1.13, 95% CI: −1.65 to −0.62, p < 0.01; I² = 66.34%) and HOMA-IR (Hedges’ g = −0.98, 95% CI: −1.35 to −0.61, p < 0.01; I² = 17.33%) compared with the controls. However, no significant changes were observed in lipid profiles. Our analysis demonstrates that BFRT exhibits the favorable effect of improving glucose metabolism in overweight/obese adults; however, current evidence does not support significant advantages of BFRT for lipid metabolism improvement. Full article

The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article

Seed oil represents a key trait in soybeans, which holds substantial economic significance, contributing to roughly 60% of global oilseed production. This research employed genome-wide association mapping to identify genetic loci associated with oil content in soybean seeds. A panel comprising 341 soybean accessions, primarily sourced from Northeast China, was assessed for seed oil content at Heilongjiang Province in three replications over two growing seasons (2021 and 2023) and underwent genotyping via whole-genome resequencing, resulting in 1,048,576 high-quality SNP markers. Phenotypic analysis indicated notable variation in oil content, ranging from 11.00% to 21.77%, with an average increase of 1.73% to 2.28% across all growing regions between 2021 and 2023. A genome-wide association study (GWAS) analysis revealed 119 significant single-nucleotide polymorphism (SNP) loci associated with oil content, with a prominent cluster of 77 SNPs located on chromosome 8. Candidate gene analysis identified four key genes potentially implicated in oil content regulation, selected based on proximity to significant SNPs (≤10 kb) and functional annotation related to lipid metabolism and signal transduction. Notably, Glyma.08G123500, encoding a receptor-like kinase involved in signal transduction, contained multiple significant SNPs with PROVEAN scores ranging from deleterious (−1.633) to neutral (0.933), indicating complex functional impacts on protein function. Additional candidate genes include Glyma.08G110000 (hydroxycinnamoyl-CoA transferase), Glyma.08G117400 (PPR repeat protein), and Glyma.08G117600 (WD40 repeat protein), each showing distinct expression patterns and functional roles. Some SNP clusters were associated with increased oil content, while others correlated with decreased oil content, indicating complex genetic regulation of this trait. The findings provide molecular markers with potential for marker-assisted selection (MAS) in breeding programs aimed at increasing soybean oil content and enhancing our understanding of the genetic architecture governing this critical agricultural trait. Full article

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article

Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article

Flavonoids constitute a broad class of naturally occurring chemical compounds classified as polyphenols, widely present in various plants, fruits, and vegetables. They share a common flavone backbone, composed of two aromatic rings (A and B) connected by a three-carbon bridge forming a heterocyclic ring (C). One representative flavonoid is chrysin, a compound found in honey, propolis, and passionflower (Passiflora spp.). Chrysin exhibits a range of biological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and anxiolytic effects. Its biological activity is primarily attributed to the presence of hydroxyl groups, which facilitate the neutralization of free radicals and the modulation of intracellular signaling pathways. Cellular uptake of chrysin and other flavonoids occurs mainly through passive diffusion; however, certain forms may be transported via specific membrane-associated carrier proteins. Despite its therapeutic potential, chrysin’s bioavailability is significantly limited due to poor aqueous solubility and rapid metabolism in the gastrointestinal tract and liver, which reduces its systemic efficacy. Ongoing research aims to enhance chrysin’s bioavailability through the development of delivery systems such as lipid-based carriers and nanoparticles. Full article

Numerous studies have demonstrated the positive effects of formulated feeds on gonadal and hepatopancreatic development of Eriocheir sinensis. However, there are limited studies on the effects of formulated feeds on the immune homeostasis and metabolism of muscle tissue in E. sinensis during the fattening period. Therefore, this study used metabolomic and lipidomic to systematically analyze the effects of formulated diets on muscle metabolism in female E. sinensis. The results indicate that the formulated feeds improved immune performance by inhibiting inflammatory responses, apoptosis and autophagy. In addition, the feed promoted amino acid metabolism and protein synthesis while decreasing muscle fatty acid metabolism. Metabolomic analysis reveal that pyrimidine metabolism is involved in the regulation of muscle physiological health in fattening female crabs. Lipidomic analysis revealed that the formulated feeds play a role in muscle immune homeostasis, amino acid and fatty acid metabolism by regulating the level of ceramide (Cer (d18:1/22:0)) in sphingolipid metabolism. Through subnetwork analysis, the functional interactions of sphingolipid metabolism with the pathways of sphingolipid signaling, apoptosis regulation, inflammatory response and lipid dynamic homeostasis were identified, which further defined the important role of sphingolipid metabolism in the regulation of muscle physiological health and metabolic homeostasis was further identified. In summary, the formulated feeds effectively promote immune homeostasis and metabolism in the muscle of female E. sinensis during the fattening period. These findings provide a solid theoretical foundation for feed formulation optimization and application in fattening practices. Full article

Background/Objectives: Neuromedin U (NMU) is a highly conserved gene encoding a neuropeptide involved in the regulation of feeding behavior and energy homeostasis. We aimed to analyze the association between NMU genetic and epigenetic variations and cardio-metabolic parameters in an Italian population to identify the role of these variants in cardio-metabolic risk. Methods: A total of 4028 subjects were randomly selected from the Moli-sani study cohort. NMU haplotypes were estimated using seven SNPs located in the gene body and in the promoter region; DNA methylation levels in the promoter region, previously associated with lipid-related variables in the same population, were also used. Results: Among the haplotypes inferred, the haplotype carrying the highest number of minor variants (frequency 16.6%), when compared with the most frequent haplotype, was positively associated with insulin levels, HOMA-IR, and diastolic blood pressure, and negatively with HDL-cholesterol. The multivariable analysis that considered methylation levels along with their interactions with SNPs showed that increased methylation levels in two close CpG sites were associated with higher levels of lipid-related variables. Conclusions: This study supports a role for NMU as a regulator of human metabolism. This finding suggests that NMU could be a potential target for preventive interventions against coronary and cerebrovascular diseases, and that NMU genetic and epigenetic variability may serve as a biomarker for cardio-metabolic risk. Full article

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article