Search Results (1,921)

We compared oxidative markers and their links to inflammation in diabetic nephropathy and hemodialysis to identify independent determinants. We studied 180 adults, 90 patients with type 2 diabetes and diabetic nephropathy and 90 patients on hemodialysis. We measured serum advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS) by enzyme-linked immunosorbent assay (ELISA). Partial correlations were adjusted for age, sex, and albumin with false discovery rate (FDR) control. Principal component analysis (PCA) summarized inflammatory indices and linear models tested predictors of AOPP and TBARS. Oxidative damage was higher in hemodialysis, with AOPP median 25.80 versus 5.06 and TBARS 8.49 versus 1.89, p less than 0.0001. C reactive protein (CRP) and mean corpuscular volume-to-lymphocyte ratio (MCVL) were higher in patients ongoing hemodialysis; systemic immune-inflammation index (SII) was higher in diabetic nephropathy. PCA yielded a dominant inflammation axis in both cohorts, 74.73 percent in hemodialysis and 85.20 percent in diabetic nephropathy. In regression, creatinine (β = 2.47, p = 0.026) predicted AOPP in hemodialysis. Dialysis vintage inversely predicted TBARS, beta minus 0.2305, p = 0.0209. In diabetic nephropathy, the PCA inflammation score predicted AOPP, β = 1.134, p = 0.0003. Protein oxidation tracked systemic inflammation in diabetic nephropathy, but not in hemodialysis. AOPP outperformed TBARS as an inflammatory partner and a practical monitoring candidate in diabetic kidney disease. Prospective studies should test for prognostic value and therapy sensitivity. Full article

Furosemide appears to contribute to the accumulation of protein-bound uremic toxins (PBUTs) and to induce adverse drug reactions. We investigated the extent to which the association between the furosemide dose and serum PBUT concentrations mediates the relationship between the furosemide dose and the symptom burden in patients with chronic kidney disease (CKD). This cross-sectional analysis included patients with CKD stages 2 to 5 from the CKD-REIN cohort and with data on the baseline serum concentrations of the free fractions of indoxyl sulphate (IS), kynurenine (KYN), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA), as measured by liquid chromatography–tandem mass spectrometry. The symptom burden was also assessed with a modified (8-item) symptom subscale from the Kidney Disease Quality of Life-36 (e.g., muscle soreness, cramps, itchy skin, dry skin, dizziness, appetite, numbness, and nausea). We used beta regressions to model the association between the furosemide dose and the symptom burden and used structural equation models to quantify the mediating effect of PBUT on this association. Among the 2053 included patients (males: 66%, median age: 68; mean estimated glomerular filtration rate: 35 mL/min/1.73 m²), those prescribed high-dose furosemide (>120 mg/day) had higher symptom burden than those not prescribed furosemide (i.e., a 5.67-point lower symptom score, 95%CI 1.41–9.93). The sum of PBUTs explained 3.78% (95%CI 0.10–18.01%) of this association. Similar results were observed for IS, KYN, and IAA, considered separately, but not for PCS, whose estimated mediation effect was nearly null. Although high-dose furosemide was associated with a greater symptom burden in patients with CKD, mediation by PBUT accumulation appeared to be minimal. Full article

Inflammation contributes to the pathogenesis of ischaemic stroke both as a long-term causal factor and through the inflammatory cascade in acute stroke. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory molecule, while interleukin-1 receptor antagonist (IL-1Ra) acts as its antagonist. Free fatty acids (FFAs) play a role in atherosclerosis formation and serve as substrates for inflammatory molecules. This study aimed to determine the potential interplay between FFAs, IL-1β, and IL-1Ra in stroke patients. A prospective analysis was conducted on 73 ischaemic stroke patients. All participants had their FFA, IL-1β, and IL-1Ra levels assessed. Significant correlations between IL-1β and certain FFAs were detected: C15:0 pentadecanoic acid (rho = 0.488), C15:1 cis-10 pentadecanoic acid (rho = 0.473), C17:1 cis-10 heptadecanoic acid (rho = 0.411), C18:0 stearic acid (rho = 0.302), C24:0 lignoceric acid (rho = −0.280), C24:1 nervonic acid (rho = −0.276), C18:2n6t linoleic acid (rho = −0.272), C17:0 heptadecanoic acid (rho = 0.241), and C13:0 tridecanoic acid (rho = 0.238). After multivariate analysis C15:0 pentadecanoic acid remained statistically significant. The strongest correlation was found between IL-1Ra and fatty acids: C15:1 cis-10-pentadecanoid acid (rho = −0.357), C18:2n6t linoleic acid (rho 0.341) and C24:1 nervonic acid (rho 0.302), but after multivariate analysis significantly correlated remained: C22:1n9 13 erucic acid (rho = 0.299), C18:3n6 gamma-linoleic acid (rho = 0.277), with close to significant correlation with C22:4n6 docosatetraenoate (rho = −0.241, p = 0.055). Certain FFAs may play a role in enhancing both pro- and anti-inflammatory responses in the early subacute phase of stroke, where inflammatory and resolving processes are ongoing. Fatty acids such as C15:0 pentadecanoic acid, C15:1 cis-10 pentadecanoic acid and C22:4n6 docosatetraenoate might be involved in pro-inflammatory responses, while C22:1n9 13 erucic acid and C18:3n6 gamma-linoleic acid in the anti-inflammatory pathways with the overlay of IL-1β and IL-1Ra. Full article

Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to generate cross-reactive antibodies, which can be especially beneficial against viruses with ever-mutating variants. Moreover, the microparticulate oral dissolving film-based vaccine approach is a non-invasive vaccine delivery platform. Methods: The vaccine design incorporated whole inactivated Delta and Omicron variants of the virus, administered at prime and booster doses, respectively, effectively encapsulated in a Poly(lactic-co-glycolic) acid (PLGA) polymer matrix, and adjuvanted with Alum to enhance immune activation. Following vaccination, serum, mucosal, and tissue samples were analyzed to evaluate humoral and cellular immune responses against the model antigen, as well as other variants such as Alpha and Beta variants, to understand the cross-reactive response. Result: In vitro evaluations confirmed the vaccine’s safety and its ability to stimulate immune responses. On administering microparticulate oral dissolving films to mice, whole inactivated delta and omicron variant-specific antibodies were observed in serum samples along with neutralizing titers in terminal week. The formulated vaccine showed significant secretory IgA antibody levels in mucosal samples. Moreover, CD4⁺ and CD8a cellular responses were observed in tissue samples of spleen and lymph nodes, along with antibodies (IgG, IgA, and IgM) detected in lung supernatant samples. Humoral and cellular cross-reactive antibodies were observed in the samples. Conclusions: This approach offers a promising platform for developing next-generation vaccines capable of inducing broad immunity. Full article

A highly active Co/Beta catalyst was prepared via ion-exchange method, in which sodium cations in the beta zeolite framework were replaced by cobalt ions using an aqueous cobalt nitrate solution. Based on XRD, SEM, TEM, XPS, and nitrogen adsorption–desorption analyses, it was confirmed that cobalt species successfully took the place of sodium ions in beta zeolite, while the cobalt species diffused with a uniform dispersion. Strong electronic coupling between cobalt species and zeolite framework oxygen stabilizes Co²⁺ sites in the material. The catalysts perform high efficiency in dye Acid Orange II (AO7) degradation reactions, which gives more than 99.5% removal efficiency at room temperature and initial pH within 10 min under low catalyst dosage. The advantages of the Co/Beta catalyst are reasonably attributed to its maximized metal−zeolite synergistic efficiency. Full article

Purpose: The aim of this review is to provide an overview of the effects of commonly used dietary supplements on soccer performance and to bridge the gap between scientific evidence and their practical application by practitioners working with elite soccer players. Methods: Relevant literature involving dietary supplement use in soccer players was identified through searches of PubMed, EMBASE, Scopus, and Web of Science. Additionally, insights were gathered from a cross-sectional online questionnaire completed by practitioners (nutritionists, physicians, sport scientists, strength and conditioning coaches, and heads of performance) working with first-division men’s teams across five European leagues. Eligible respondents were over 18 years old with >2 years of experience in elite sport. The 20-question survey, designed on Qualtrics and pilot-tested for content validity, covered practitioner background, beliefs about supplementation, and real-world practices. The study was approved by the Ethical Independent Committee in Genoa, Italy (Ref. 2020/12). Results: Among performance-enhancing supplements, caffeine has been shown to improve endurance, sprint performance, power, and cognitive function, while creatine consistently enhances short-duration, high-intensity efforts. Beta-alanine and sodium bicarbonate help reduce the buildup of acidity in muscles during repeated high-intensity exercise, supporting repeated sprint performance. For hydration and endurance support, dietary nitrates improve blood flow and oxygen delivery to muscles, and glycerol enhances fluid retention in hot environments and during compressed match schedules, where players compete in multiple matches within a short recovery window. Regarding recovery aids, protein and tart cherry supplementation have been shown to accelerate recovery, reduce muscle damage, and support training adaptations. Field insights revealed that creatine and caffeine were widely adopted by practitioners (>90%), with protein powders also commonly recommended (>80%). In contrast, beta-alanine, tart cherry, and dietary nitrates were only partially integrated into daily practice (30%, 32%, and 48.5%, respectively), while sodium bicarbonate (24%) and glycerol (10.5%) were used by a minority. Conclusions: Although scientific evidence provides a strong foundation for the efficacy of dietary supplements, their translation into elite soccer practice is shaped by a range of practical factors, including cultural resistance, taste preferences, gastrointestinal side effects, established team routines, and individual player preferences. These findings highlight the importance of targeted education for players and staff, individualized supplementation plans, and close collaboration between nutritionists, coaches, and medical teams. However, our survey did not directly assess reasons for non-implementation. In addition to practical barriers reported by practitioners, unfamiliarity with current evidence likely contributes to this evidence–practice gap. Full article

Mercury exposure has been linked to male infertility. Given that mercury chloride (HgCl₂) may promote an oxido-inflammatory milieu associated with pathophysiological derangements, it is hypothesised that Thymoquinone (TQ), an antioxidant and anti-inflammatory agent, may mitigate the gradual harmful effects of mercury exposure on rat testes, epididymis, and hypothalamus, as these organs are vital to reproductive function. To test this hypothesis, 40 rats (strain: Wistar; sex: male) were randomly assigned to five cohorts of eight rats each. After a 7-day acclimation, treatments were dispensed for 28 consecutive days accordingly: Cohort I: distilled water only, as control; Cohort II: HgCl₂ only (20 µg/mL); Cohort III: TQ only (2.5 mg/kg); Cohort IV: HgCl₂ + TQ (20 µg/mL + 2.5 mg/kg); and Cohort V: HgCl₂ + TQ (20 µg/mL + 5 mg/kg). Co-treatment with TQ preserved the body and organ weight of the HgCl₂ exposed animals. However, TQ did not reduce HgCl₂-induced dysfunction in sperm function and morphology. The serum follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone were increased significantly (p < 0.05) by TQ co-treatment, while decreasing the prolactin level. TQ administration also increased (p < 0.05) testicular enzymes, including alkaline phosphatase (ALP), lactate dehydrogenase (LDH), acid phosphatase (ACP), and glucose-6-phosphate dehydrogenase (G6PD) activities, which HgCl₂ decreased. TQ administration increased (p < 0.05) HgCl₂-induced decreases in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), glutathione-s-transferase (GST), and total sulfhydryl group (TSH) levels in the testes, epididymis, and hypothalamus of experimental rats. Further, TQ reduced HgCl₂-mediated increases in RONS-reactive oxygen and nitrogen species; LPO–lipid peroxidation; PC–protein carbonyl formation; and XO–xanthine oxidase activity. Furthermore, levels of inflammatory biomarkers, including tumour necrosis factor alpha (TNF-α), nitric oxide (NO), interleukin-1 beta (IL-1β), and myeloperoxidase (MPO), were decreased (p < 0.05) in the co-treated groups, with a higher dose of TQ (5.0 mg/kg) showing a more pronounced protective effect. Additionally, TQ co-administration increased Bax and decreased Bcl-2 and p53 protein levels (p < 0.05), thereby protecting the rats’ testes, epididymis, and hypothalamus from HgCl₂-induced apoptosis. Molecular docking simulation analysis revealed TQ interaction dynamics with PPAR-α and PPAR-δ to suppress NF-kB-mediated pro-inflammatory sequela as well as activate Nrf-2-mediated antioxidant defence system. These predicted biological effects of TQ resonate with the findings from the in vivo studies. Therefore, supplementation with TQ may help reduce chemical-induced toxicities, including HgCl₂‘s reproductive toxicity. Full article

Electroencephalography (EEG) electrodes require low impedance, high biocompatibility, and long-term performance. Conventional Ag/AgCl wet electrodes achieve low impedance but suffer from dehydration and skin irritation, whereas dry electrodes often induce discomfort or exhibit high impedance. To address these limitations, this study engineered a hydrogel-based electrode by incorporating PEDOT:PSS and the nonionic surfactant Triton X-100 into an acrylic acid hydrogel matrix. The flexible acrylic acid backbone, conductive PEDOT:PSS domains, and the nanofibrillar network promoted by Triton X-100 simultaneously enhanced mechanical compliance and electrical stability. In addition, the structural rearrangement of PEDOT:PSS was verified through morphological analyses. The fabricated electrode exhibited a modulus comparable to human soft tissue, demonstrated strong interfacial adhesion in shear tests, and significantly reduced skin–electrode contact impedance. Furthermore, EEG measurements showed that the hydrogel electrode achieved alpha- and beta-band signal power comparable to commercial Ag/AgCl electrodes. These findings establish the PEDOT:PSS–Triton X-100 hydrogel electrode as a promising candidate to replace conventional wet and dry electrodes for reliable EEG applications. Full article

Background/Objectives: In this proof-of-concept study, the objective was to evaluate the phenotypic CarbaLux combination rapid test in terms of guiding the therapy of infections caused by multidrug-resistant Gram-negative bacteria with carbapenemase inhibitors and carbapenems, and to compare its results and practicability with standard diagnostic methods. Methods: In the classical CarbaLux test, a fluorescent carbapenem serves as a UV–visible diagnostic surrogate for clinically used carbapenem antibiotics. When exposed to extracted carbapenemases from bacterial colony growth on agar plates, fluorescence rapidly disappears, showing whether monotherapy with carbapenems is possible or must be rejected. It was expected that a specific inhibitor that protects imipenem or meropenem from enzymatic deactivation during antibacterial therapy would perform the same in vitro with fluorescent carbapenem and preserve its fluorescence. The new additional CarbaLux combination test is used if the classic test is positive for carbapenemases: a classic test tube pre-dosed with fluorescent carbapenem is spiked with cloxacillin; with recently launched carbapenemase inhibitors, e.g., avibactam, relebactam, zidebactam, nacubactam, or vaborbactam; or with picolinic acid. Fourteen Enterobacterales and six Acinetobacter baumannii isolates were analyzed. Results: At fixed concentrations, the new inhibitors protected fluorescent carbapenem from bacterial KPC-mediated inactivation and partially from AmpC beta-lactamase-mediated inactivation. In addition, avibactam also effectively inhibited OXA-48-like enzymes. Cloxacillin selectively inhibited AmpC beta-lactamases extracted from Enterobacter complex species. Non-therapeutic picolinic acid was specific for metallo-beta-lactamases and thus identified infections by pathogens that cannot be treated with carbapenems alone or in combination. Conclusions: Inhibitor/fluorescent carbapenem mixtures corresponding to therapeutic inhibitor/carbapenem combinations allow us to visualize the efficacy of carbapenemase inhibitors. The in vitro results are consistent with clinical experience regarding combination therapy. Enzymatic assays provide a rapid yes/no answer for carbapenem mono- or combination therapy and offer several advantages over current carbapenemase testing methods. In contrast to PCR and lateral flow tests, which only target a selection of carbapenemases, enzymatic assays work by employing a reproducible phenotypic mechanism. They are simpler, broader in scope, and more cost-effective; they can also detect antimicrobial heteroresistance or AmpC beta-lactamase hyperproduction, which is normally undetected when performing automated antibiotic susceptibility testing. The new tests are suitable for clinical diagnosis, public health purposes, and infection control. Full article

Preterm prelabor rupture of membranes (PPROM) is a leading cause of preterm birth and significant neonatal morbidity. The vaginal microbiome is implicated in its pathogenesis, but its detailed characteristics and functional consequences remain to be fully elucidated. This study aimed to provide a comprehensive, multi-faceted analysis of the vaginal microbiome and its functional potential in pregnant women with PPROM compared to healthy term controls. We collected vaginal fluid samples from eight PPROM and seven healthy control (HC) pregnant women. The vaginal microbiome was analyzed using 16S rRNA gene sequencing. We assessed community composition and state types (CSTs), alpha and beta diversity, co-occurrence networks, and predicted functional pathways using PICRUSt2. A molecular bacterial vaginosis (molBV) score was also calculated to determine the clinical relevance of the dysbiosis. The PPROM microbiome was characterized by a significant depletion of Lactobacillus crispatus–dominated communities (CST I) and a shift towards L. iners–dominated (CST III) or polymicrobial (CST IV) communities, which was consistent with a BV-positive molBV score. Alpha diversity was significantly higher in the PPROM group, and beta diversity analysis confirmed a distinct microbial structure between the two groups. Co-occurrence network analysis revealed a collapse of the protective, Lactobacillus-centered network in the PPROM group, which was replaced by a densely interconnected network of anaerobic bacteria with Gardnerella vaginalis as a key hub. Functionally, the PPROM microbiome was enriched for amino acid biosynthesis pathways, in contrast to the HC group, which was enriched for nucleotide and peptidoglycan biosynthesis. PPROM appears to be linked with a complex vaginal dysbiosis that encompasses significant alterations in microbial composition, diversity, interactions, and functional potential. These findings highlight the vaginal microbiome as a critical factor in the pathogenesis of PPROM and suggest its potential for risk stratification and as a therapeutic target to improve pregnancy outcomes. Full article

This research reports ruminal and fecal microbiota composition of lactating dairy cows enrolled in a study aimed at investigating the effects of a fermentation extract derived from Bacillus licheniformis (BLFE), monensin (Rumensin^®; R), and their interactions on feed efficiency (FE, FE = milk yield/DMI). In a completely randomized design, 48 Holstein cows at 108 ± 35 days in milk were matched for parity and assigned to monensin (0 or 17.6 g/kg of DM) and BLFE (0 or 166 mg/kg of DM) in a 2 × 2 factorial arrangement. Treatments were fed daily for 63 d, including a 21 d adaptation period followed by a 42 d measurement period (P2). On d 38 and d 39 of P2, rumen-fluid (RF) and fecal samples were collected. DNA from RF and feces was sequenced using 16S rRNA gene-amplicon sequencing on an Illumina MiSeq platform. Fecal and RF volatile fatty acid (VFA) concentrations were analyzed, and propionate/acetate (P: A) was determined. The BLFE increased milk yield (3.3 kg/d) and FE (1.20 to 1.28), when fed alone rather than with monensin, while monensin increased energy-corrected milk yield (2.5 kg/d, p < 0.05), regardless of the BLFE in the diet. The BLFE tended to increase ruminal Firmicutes/Bacteroidetes (F: B) when fed alone, while alpha and beta diversities remained unmodified. The BLFE increased the abundances of Bifidobacterium (p = 0.02) and Erysipelotrichaceae_UCG-002 (p = 0.01) in RF, whereas monensin increased and decreased the abundances of Oscillospirales_ge (p = 0.02) and an unclassified Clostridia genus (p = 0.03), respectively. The monensin-suppressed Clostridia were negatively associated with ruminal P: A (r = −0.66; p < 0.01) and feed efficiency (r = −0.30; p = 0.04). The BLFE and monensin interactively affected several fecal genera (p < 0.05), but they had negligible or weak correlations with fecal P: A and FE. Overall, the results showed the ability of dietary supplementations of monensin and BLFE to increase milk production performance and FE by modulating ruminal rather than lower-gut microbiota composition, this is predominantly attributed to the ratio between the Firmicutes and Bacteroidetes abundances in lactating dairy cows. Full article

Gut microbiota changes have emerged as central players in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and inflammatory bowel disease (IBD). Although these diseases affect distinct primary organs, they share converging mechanisms driven by dysbiosis, including loss of beneficial short-chain fatty acid-producing taxa such as Faecalibacterium prausnitzii and Roseburia, enrichment of pro-inflammatory Enterobacteriaceae, and disruption of bile acid and tryptophan metabolism. These shifts compromise epithelial barrier integrity, promote the translocation of microbial products such as lipopolysaccharide, and trigger toll-like receptor 4-mediated activation of inflammatory cascades dominated by tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta. In MASH, this dysbiotic environment fuels hepatic inflammation, insulin resistance, and fibrogenesis, while in IBD it sustains chronic mucosal immune activation. Shared features include impaired butyrate availability, altered bile acid pools affecting farnesoid X receptor and Takeda G protein-coupled Receptor 5 signaling, and defective aryl hydrocarbon receptor activation, all of which link microbial dysfunction to host metabolic and immune dysregulation. Understanding these overlapping pathways provides a deeper understanding of the role of the gut-liver and gut-immune axes as unifying frameworks in disease progression. This narrative review synthesizes current evidence on gut microbiota in MASH and IBD, underscoring the need for longitudinal, multi-omics studies and microbiome-targeted strategies to guide personalized therapeutic approaches. Full article

Heracleum persicum Desf. ex Fischer, a species of the Apiaceae family, is endemic to Iran and has been historically utilized as a spice, condiment, and medicinal plant. The plant produces seeds that represent a potential new source of vegetable oil. In this study, the oil from these seeds was extracted using a solvent, and its physical, chemical, and nutritional properties were investigated. The oil extraction yield was determined to be 12.62%. Oleic acid (61.11%) and linoleic acid (25.84%) were identified as the predominant fatty acids in the extracted oil. Among its phytosterols, beta-sitosterol (65.6%) and stigmasterol (14.0%) were the most abundant. Furthermore, this oil exclusively contained alpha-tocopherol at a relatively high concentration (1610.9 ppm). The chlorophyll and carotenoid contents of the extracted oil were 28.34 mg/kg and 4.95 mg/kg, respectively. Regarding its nutritional indices, the atherogenic index, thrombogenic index, and hypocholesterolemic to hypercholesterolemic ratio were 0.13, 0.24, and 9.77, respectively. In conclusion, considering its unique oil composition and qualitative characteristics, this oil holds promise as a novel source of vegetable oil and a valuable byproduct of Heracleum persicum. Full article

Background: Cardiometabolic syndromes, including diabetes, obesity, and metabolic syndrome, significantly contribute to cardiovascular fibrosis, a major driver of heart failure. Non-coding RNAs (ncRNAs)—notably microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—have emerged as critical epigenetic regulators of fibrotic remodeling. Recent studies indicate that widely used metabolic modulators can influence ncRNA expression, potentially impacting on cardiovascular fibrosis. This review synthesizes evidence on the interplay between metabolic therapies and ncRNA regulation, with emphasis on therapeutic and biomarker potential of miRNAs. Methods: A literature search was manually curated and conducted on PubMed for studies published mainly in the last decade and evaluating the effects of metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, glucagon-like peptide 1 (GLP-1) receptor agonists, and fatty acid oxidation inhibitors on ncRNA expression in the context of cardiovascular fibrosis. Data from in vitro, in vivo, and clinical studies were extracted and categorized by drug class, ncRNA target, and functional outcomes. Results: Several metabolic modulators specifically downregulate pro-fibrotic (miR-21, miR-92, H19, and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)) and upregulate anti-fibrotic ncRNAs (miR-29, miR-133a, miR-711, miR-133a, miR-30a and miR-200 family). This results in global attenuation of the transforming growth factor- beta (TGF-β) signaling, which limits extracellular matrix (ECM) accumulation thus improving myocardial compliance. Across drug classes, changes in ncRNA profiles paralleled improvements in fibrosis-related endpoints. Conclusions: Metabolic modulators exert anti-fibrotic effects partly through ncRNA regulation, offering novel therapeutic strategies and potential biomarkers for cardiovascular fibrosis in cardiometabolic disease. Targeting metabolic–ncRNA crosstalk may enable more precise and synergistic interventions for preventing or reversing pathological remodeling. Full article

FVPB1, a novel heteropolysaccharide, was extracted from the Flammulina velutipes fruiting body, and its structure was determined by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy. FVPB1 demonstrated efficacy in inhibiting lipid accumulation in Raw264.7 cells and zebrafish, as well as in reducing weight gain and ameliorating liver injury in high-fat diet-induced mice. High concentration of FVPB1 significantly increased serum ApoA1 levels, while all tested doses (low, medium, and high) reduced serum ApoB levels in mice. Intervention with FVPB1 significantly increased the mRNA expression of Lcat and Cyp7a1 enzymes while markedly reducing the transcriptional level of Hmgcr reductase. Additionally, low concentration of FVPB1 enhanced CYP7A1 protein expression, whereas medium and high concentrations of FVPB1 promoted LCAT protein expression. Medium and high concentrations of FVPB1 significantly enhanced bile acid excretion in mice, with the high dose additionally promoting fecal sterol output. Alpha and beta diversity analyses demonstrated that a high-fat diet induced substantial dysbiosis in the gut microbiota of mice, characterized by reduced microbial diversity and richness. Intervention with FVPB1 significantly modulated the structural composition of the intestinal microbiota in high-fat diet-fed mice. Therefore, FVPB1 exerts lipid-lowering effect in high-fat diet-fed mice by modulating cholesterol metabolism and ameliorating gut microbiota dysbiosis. Full article