Search Results (4,708)

Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-κB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), NF-κB, Inhibitor of NF-κB α (IκBα), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the IκBα/NF-κB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism. Full article

Chronic wounds represent a substantial and growing clinical burden, yet durable healing remains difficult to achieve in a large proportion of patients. The skin microbiome plays a central role in this challenge: in healthy tissue, resident microorganisms support barrier integrity and calibrate immune responses, whereas in chronic wounds, community disruption—often combined with persistent biofilm formation—drives non-resolving inflammation, impairs re-epithelialisation, and increases antimicrobial tolerance. As antibiotic resistance escalates, these features strengthen the rationale for microbiome-directed strategies that target wound ecology while reducing reliance on conventional antimicrobials. Current evidence is still dominated by mechanistic and preclinical studies, with only early clinical signals for selected approaches; therefore, next-generation probiotics, including Lactiplantibacillus/Lactobacillus spp., as well as defined prebiotic and postbiotic formulations, should be interpreted as promising adjuncts rather than clinically established therapies. Causal mechanisms, optimal formulations, reproducibility, and patient-level determinants of response remain insufficiently defined, representing a critical knowledge gap that limits translation. Here, we synthesise current evidence linking microbial ecology to key wound-healing pathways and propose a precision framework that integrates metagenomics, transcriptomics, metabolomics, and spatial profiling to map host–microbe interactions, identify predictive biomarkers, and guide stratified therapy. We further highlight combinatorial approaches pairing ecological engineering with biofilm-disruptive materials and immune-modulatory molecules. Realising the potential of these interventions will require mechanism-resolved clinical trials, standardised outcome frameworks, and patient stratification tools—advances that could improve chronic wound management while reducing selective pressure for antimicrobial resistance. Full article

Onion peel extract (OPE) is rich in polyphenolic compounds with antimicrobial potential. Salmonella Enteritidis (SE) infection in young broiler chicks causes morbidity, reduced growth, and contributes to human gastroenteritis through contaminated poultry products. The spleen is a key secondary lymphoid organ coordinating systemic responses to pathogens in chicken. This study evaluated how dietary OPE influences spleen metabolic profiles during SE infection. Day-old Ross 708 male chicks (n = 128) were assigned to four treatments: CON, CON-SE, OPE (6 g/kg), and OPE-SE. Chicks in CON and OPE received sterile broth, whereas CON-SE and OPE-SE received 2.25 × 10⁸ CFU/mL SE at 2 d of age. At 5 and 12 dpi, spleens from six chicks per treatment were collected for untargeted HPLC-MS metabolomics. A total of 857 metabolites were identified and analyzed using MetaboAnalyst 6.0 (p < 0.05; fold change ≥ 2.0; VIP score > 1.0). In CON-SE chicks, energy generating metabolites (6-phosphogluconic acid, methylmalonic acid, propionic acid) increased, while 13,14-dihydro-15-keto-prostaglandin D2 and kynurenic acid decreased. Dietary OPE elevated several dipeptides (L-Val-Gly, L-Leu-Gly, Gly-Gly-Leu, L-Val-L-Met) and reduced ATP linked metabolites (3,6-di-O-methyl-beta-D-glucose and 3-O-beta-D-galactosyl-sn-glycerol). Enrichment analysis showed that SE infection altered valine, leucine, and isoleucine degradation and aromatic amino acid biosynthesis, whereas OPE enriched galactose and biotin metabolism in uninfected chicks, but enriched tryptophan, taurine and hypotaurine metabolism in SE-infected chicks. Overall, dietary OPE optimized response of metabolic pathways associated with immune activation, unlike corresponding pathways in CON-SE birds. Full article

Flavonoids are essential secondary metabolites that predominantly affect flower pigmentation in plants. Understanding the molecular mechanisms underlying flower color divergence is crucial for ornamental plant breeding. This study aimed to elucidate the factors responsible for the differences in color between white-petaled Cosmos bipinnatus and orange-petaled Cosmos sulphureus. We employed an integrated approach combining untargeted LC–MS/MS metabolomics and high-throughput transcriptome sequencing of fresh petals to analyze pigment composition and differential gene expression. Petal pigment extraction, total flavonoid quantification, and metabolomic profiling consistently revealed that differences in flavonoid abundance are responsible for flower color divergence between the two species. In contrast, carotenoids, previously considered potential contributors to flower coloration, were neither evident in the oil phase of the pigment extracts nor detected by metabolomic analysis. Flavonoid compounds accumulated at relatively high levels in the orange petals of C. sulphureus, reaching 11.36 times that of C. bipinnatus, contributing to its bright appearance. Transcriptomic analysis revealed differences in gene expression patterns between the two species, highlighting key candidate genes involved in the flavonoid biosynthesis pathway, such as chalcone synthase. These findings indicate that the orange coloration of C. sulphureus may be associated with CHS-regulated accumulation of naringenin chalcone and downstream compounds in the flavonoid metabolic pathway after CHS, providing valuable theoretical support for a deeper understanding of the causes underlying the differences in flower color between C. bipinnatus and the orange-petaled C. sulphureus. Full article

Elucidating the interactions among microbial communities in the Sichuan paocai fermentation system is of great significance for ensuring the safety and quality of paocai. In this study, the interaction between Bacillus subtilis Y61 and Weissella paramesenteroides (CWP) was preliminarily verified through the culture of CWP using the cell-free supernatant derived from Y61. Building on this, a transwell chamber was employed to spatially isolate the two bacteria. Combined with transcriptomic and metabolomic profiling, the underlying interaction mechanism was revealed. Weissella paramesenteroides (CWP) exhibited enhanced growth in the cell-free supernatant of Bacillus subtilis Y61, confirming a cross-feeding relationship between the two strains. In the transwell chamber, the promoting effect was most significant when Weissella paramesenteroides (CWP) was in the upper compartment and Bacillus subtilis Y61 in the lower compartment. Transcriptomic analysis showed that Weissella paramesenteroides (CWP) significantly upregulated genes involved in fatty acid synthesis and metabolism while downregulating those related to amino acid anabolism (p < 0.05). Metabolomic analysis further revealed that metabolites secreted by Bacillus subtilis Y61, including the key metabolites arginine and isovaleric acid, were markedly depleted during co-culture. Exogenous supplementation assays revealed that the combination of 0.1 g arginine and 2 mg isovaleric acid exhibited the strongest growth-promoting effect on Weissella paramesenteroides (CWP). Collectively, these results demonstrated that Bacillus subtilis Y61 promoted the growth of Weissella paramesenteroides (CWP) through cross-feeding via the extracellular secretion of the key metabolites arginine and isovaleric acid. Full article

Myopia is increasingly recognized as an inflammatory ocular disease. Vitamin D₃ is a potential modulator of the gut–eye axis, but its role in inflammation-induced myopia remains unclear. This study investigated whether vitamin D₃ supplementation attenuates myopia progression by regulating retinal inflammation, gut microbiota composition, and microbiota-derived metabolites in a TGF-β2–induced myopia model. Three-week-old Brown Norway rats received weekly periocular TGF-β2 injections with or without daily oral vitamin D₃, and myopia development was evaluated on days 1 and 21 by axial length and refractive error. Cecal contents were analyzed for α- and β-diversity and taxonomic differences, and day-21 serum underwent untargeted metabolomic profiling of microbiota-derived metabolites, including bile acids and imidazole derivatives; Spearman correlation linked microbial or metabolic alterations with myopia progression. TGF-β2 induced axial elongation, myopic refractive shifts, and upregulated retinal pro-inflammatory cytokines (p-NFκB, IL-1β, TNF-α), while vitamin D₃ supplementation markedly attenuated myopia progression and retinal inflammation. Cecal α-diversity did not differ among control, vitamin D₃, TGF-β2, and TGF-β2+vitamin D₃ groups, but vitamin D₃ significantly reshaped β-diversity and reduced the Firmicutes/Bacteroidota ratio. Distinct metabolite profiles were observed, with the vitamin D₃ group showing reduced hyodeoxycholic acid and elevated imidazole derivatives (imidazolepropionic and methylimidazoleacetic acids). Vitamin D₃ supplementation attenuated myopia progression by reducing retinal inflammation and concurrently reshaping the gut microbiome and its metabolites compared to the control and myopic groups. These results underscore the potential of vitamin D₃ to modulate the gut–retina axis as a nutritional approach for mitigating myopia development. Full article

Alzheimer’s disease (AD) lacks effective disease-modifying therapeutics. Probiotics, promising neuroprotective candidates, exert benefits mainly by modulating gut-brain-axis (GBA) signaling. This study explored the anti-AD effects and mechanisms of Rhodopseudomonas pseudopalustris (R. pse). Using Caenorhabditis elegans (C. elegans) AD models, we evaluated AD-related phenotypes (learning deficits, paralysis) after R. pse administration, and performed genetic analysis and metabolomic profiling to clarify its regulatory pathways and metabolites. Mechanistically, R. pse significantly alleviated AD-related phenotype in C. elegans. It upregulated γ-glutamylcysteine synthetase (GCS-1) to enhance the glutathione (GSH)-dependent antioxidant defense. Knockout of the oxidation repair enzyme methionine sulfoxide reductase A-1 (MSRA-1) abolished the neuroprotective effects of R. pse, which was rescued by methionine. R. pse also activated activating transcription factor 7 (ATF-7)-mediated innate immunity and transforming growth factor β (TGF-β) signaling, with pantothenic acid as its functional metabolite. Collectively, R. pse is a potential anti-AD bacterium that mitigates AD model pathogenesis by enhancing the cellular antioxidant capacity, providing experimental evidence for bacteria-based AD interventions. Full article

To further investigate altitude-associated variations in gut microbiota and serum metabolites of plateau zokors (Eospalax baileyi) and elucidate their adaptive mechanisms to high-altitude environments, we performed fecal metagenomic sequencing and serum metabolomic profiling (Q200 platform) on individuals from high (3700 m, n = 6) and low (2700 m, n = 6) elevations, followed by integrated analysis of microbial and metabolomic datasets. Results indicated that in high-altitude plateau zokors, the relative abundance of Firmicutes decreased, while that of Bacteroidota increased. The dominant genera within this group were identified as Bacteroides and unclassified members of the Lachnospiraceae family. Moreover, the abundances of Bacteroides and unclassified members of the Muribaculaceae family increased with elevation. At the species level, seven fully annotated differentially abundant taxa were identified: Candidatus Amulumruptor caecigallinarius, Schaedlerella arabinosiphila, Muribaculum gordoncarteri, Heminiphilus faecis, Prevotellamassilia timonensis, Staphylococcus aureus, and Bacteroides graminisolvens. KEGG enrichment analysis indicated significant upregulation (p < 0.05) of energy supply pathways, such as oxidative phosphorylation, and antioxidant-related pathways, including β-alanine and lysine metabolism, in the high-altitude group. Conversely, cysteine and methionine metabolism pathways were markedly downregulated (p < 0.05). Serum levels of ursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) were significantly elevated (p < 0.05), while deoxycholic acid (DCA) levels decreased (p < 0.05). In conclusion, the composition and function of gut microbiota, along with serum metabolite profiles, differ significantly (p < 0.05) between plateau zokors from different altitudes. Through synergistic interactions between gut microbiota and host metabolites, plateau zokors develop adaptive mechanisms that integrate energy metabolism, oxidative stress response, intestinal barrier integrity, and mucosal immunity. This ultimately facilitates their acclimatization to high-altitude extreme environments characterized by hypoxia and low temperatures. Full article

This study investigated the effects of dietary sodium butyrate supplementation on blood gas profiles, biochemical parameters, and untargeted plasma metabolomics in tumbler pigeons. Eighty tumbler pigeons of similar age, body weight, and training intensity were randomly allocated into four groups: a control group without sodium butyrate supplementation (CON) and three sodium butyrate-supplemented groups receiving 6 mg/d (T1), 12 mg/d (T2), and 18 mg/d (T3), respectively. All birds were maintained under identical husbandry conditions and fed the same basal diet throughout a 40-day experimental period consisting of a 10-day acclimation phase and a 30-day feeding trial. Results showed that dietary sodium butyrate supplementation significantly improved dry matter digestibility, with T2 and T3 exhibiting higher values than CON (p < 0.05), while metabolizable energy utilization was significantly increased in T3 compared with CON (p < 0.05). Sodium butyrate supplementation also significantly altered several blood gas parameters associated with acid–base balance and gas exchange. In addition, antioxidant enzyme activities were enhanced, with SOD, CAT, GSH-Px, and T-AOC activities significantly increased in supplemented groups compared with CON (p < 0.01). Furthermore, sodium butyrate supplementation significantly modulated inflammatory responses, increasing IL-10 concentrations (p < 0.01) while decreasing IL-6 and IL-8 levels (p < 0.01). Untargeted metabolomic analysis revealed significant alterations in pathways related to lipid metabolism, amino acid metabolism, and inflammatory regulation. In conclusion, dietary sodium butyrate supplementation influenced nutrient utilization, blood physiological parameters, antioxidant capacity, inflammatory status, and plasma metabolic profiles in tumbler pigeons. Among the tested supplementation levels, 18 mg/d sodium butyrate was associated with the most favorable overall physiological responses. These findings provide a basis for future investigations into the physiological and metabolic effects of sodium butyrate supplementation in competitive pigeons. Full article

Background and Objectives: Maternal nutrition during pregnancy has been associated with fetal development and long-term health trajectories through mechanisms potentially involving epigenetic and metabolic programming. However, the molecular mediators linking dietary quality to fetal biochemical profiles remain poorly characterized. This exploratory pilot study aimed to investigate associations between maternal nutritional adequacy and the amniotic-fluid metabolomic profile during the second trimester. Materials and Methods: In this prospective study, AF samples from 41 pregnant women undergoing second-trimester amniocentesis were analyzed using gas chromatography–mass spectrometry (GC-MS). Nutritional status was assessed via the FIGO Nutrition Checklist. Subjects were divided into two groups based on dietary adequacy (FIGO Score >5 vs. ≤5). Multivariate analysis (PLS-DA, VIP scores, volcano plots) and pathway enrichment were performed to identify discriminatory metabolites. Results: Exploratory metabolomic analysis suggested differences between the two nutritional groups. Several candidate metabolites, including stearic acid, lactic acid, proline, and scyllo-inositol, contributed to the observed differences between groups. These features may provide preliminary hypotheses regarding energy-, amino acid-, and lipid-related biochemical pathways. Conclusions: Maternal dietary quality was associated with differences in the amniotic-fluid metabolomic profile. These preliminary findings support further investigation of amniotic-fluid metabolomics as a potential tool for studying the fetal biochemical environment. Full article

Background/Objectives: Ultra-processed foods (UPFs) are increasingly recognized as dietary exposures associated with cardiometabolic, hepatic, and neurocognitive outcomes. However, UPFs are often treated mainly as nutrient-poor foods, whereas their processing-related features may perturb gut–liver–brain communication. This review examines whether metabolic dysfunction-associated steatotic liver disease (MASLD) can be conceptualized as a hepatic metabolic amplifier linking UPF exposure to cognitive aging. Methods: We conducted a structured narrative search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus from January 2010 to 11 May 2026 across four evidence modules: UPFs and MASLD/NAFLD; UPFs and cognitive aging or dementia; UPFs and gut–liver–brain mechanisms; and MASLD/NAFLD and cognitive aging. Representative studies were prioritized according to direct relevance to the proposed axis, study design, exposure and outcome validity, mechanistic specificity, and contribution to major evidence gaps. Results: Observational and mechanistic evidence links higher UPF consumption with liver steatosis, MASLD/NAFLD-related outcomes, cognitive decline, cognitive impairment, stroke, and dementia-related outcomes, although causality remains incompletely established and residual confounding is important. Candidate pathways include food-matrix disruption, rapid eating, displacement of microbial substrates, selected additives and processing-derived compounds, intestinal barrier dysfunction, metabolic endotoxemia, bile acid signaling, hepatic lipotoxicity, systemic inflammation, vascular dysfunction, and neuroimmune activation. Many pathways overlap with general cardiometabolic dysfunction; the processing-centered contribution lies in positioning industrial formulation as an upstream exposure and MASLD as a hepatic node that may amplify gut-derived and metabolic signals relevant to brain aging. Conclusions: A processing-centered gut–liver–brain framework integrates UPFs, MASLD, and cognitive aging as linked metabolic-aging phenomena. Future studies should test UPF substitution using liver imaging, microbiome profiling, metabolomics, bile acid and inflammatory biomarkers, neuroimaging, and cognitive assessment. Full article

Myostatin (MSTN) is a well-established negative regulator of skeletal muscle growth; however, its role in bone metabolism and osteogenic differentiation remains incompletely understood. In this study, untargeted and targeted metabolomic analyses were performed to investigate the metabolic effects of the MSTN^Del73C mutation during osteogenic differentiation of sheep bone marrow mesenchymal stem cells (BMSCs). Metabolomic profiles were analyzed in wild-type and MSTN^Del73C mutant BMSCs at 0, 7, and 14 days of osteogenic induction. During normal osteogenic differentiation, metabolites related to glycerophospholipid metabolism were repeatedly detected among significantly altered features, accompanied by marked increases in multiple lysophospholipid subclasses, including lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). In contrast, MSTN^Del73C mutation was associated with significant reductions in several LPC and LPI species (p < 0.01 or p < 0.001), suggesting altered lipid metabolic profiles during differentiation. Targeted metabolomic validation further confirmed the altered abundance pattern of LPC 18:2. Collectively, these findings suggest that MSTN mutation is closely associated with metabolic remodeling during osteogenic differentiation and suggest potential involvement of glycerophospholipid-related metabolites involved in MSTN-related regulation of sheep BMSC osteogenesis. Full article

This study aimed to characterize metabolomic changes in the eye lens of senescence-accelerated OXYS rats in comparison with control Wistar rats, and to identify biochemical shifts associated with genotype, age, and cataract progression. Cataract severity was clinically graded. Rats’ lenses were analyzed using quantitative ¹H NMR spectroscopy at 3.6 and approximately 4.5 months of age. A total of 43 metabolites were quantified. We found that at 3.6 months of age, OXYS lenses exhibited a significant accumulation of 17 metabolites, primarily amino acids, compared to Wistar rats, suggesting an imbalance between amino acid uptake and crystallin biosynthesis. However, by 4.5 months, OXYS lenses exhibited rapid metabolic changes characterized by significant decreases in amino acid, glucose, and key energy/antioxidant markers, including NAD, adenylate energy charge, and hypotaurine. Clinical cataract grade (Grade 2 vs. 3) had a negligible impact on the overall metabolomic profile. Our results indicate that profound metabolic reorganization, including an initial amino acid excess followed by energy and antioxidant depletion, precedes the morphological manifestation of cataracts in OXYS rats. We suggest that a biochemical “point of no return” occurs early in cataractogenesis, while subsequent increase in lens opacification is a secondary consequence of preexisting metabolic disturbances. Full article

Sperm cryopreservation is important for livestock breeding and germplasm conservation, but freeze–thaw injury can impair ram sperm quality through oxidative stress, membrane damage, and metabolic disturbance. This study evaluated the concentration-dependent effects of kaempferol supplementation on the cryopreservation quality of semen from Yuansheng Aite dairy rams. Qualified ejaculates were pooled and randomly allocated to five equally spaced kaempferol treatment groups: 0, 25, 50, 75, and 100 μg/mL. Post-thaw sperm motility, oxidative stress status, ATP-related energy metabolism, acrosome integrity, and multi-omics profiles were evaluated. Data were analyzed using appropriate parametric or non-parametric tests after assessment of normality and homogeneity of variance. Orthogonal polynomial analysis was performed to evaluate linear and nonlinear dose–response patterns across the tested kaempferol concentrations. Kaempferol supplementation significantly affected PM, VCL, and VAP, while RPM, LIN, WOB, and VSL were not significantly affected. No significant linear effect was observed for the motility parameters, whereas VCL exhibited a significant quadratic response to kaempferol concentration. Based on the observed overall responses of sperm motility, antioxidant capacity, oxidative stress markers, ATP content, and acrosome integrity, 25 μg/mL kaempferol showed the most favorable overall profile among the tested concentrations and was selected for subsequent mechanistic analyses. Proteomic and metabolomic analyses suggested that the protective effects of kaempferol may be associated with pathways related to focal adhesion, cytoskeletal organization, oxidative phosphorylation-related energy metabolism, and central carbon metabolism. These findings indicate that moderate kaempferol supplementation may improve the post-thaw quality of Yuansheng Aite dairy ram semen, although further fertility-oriented studies are needed to confirm its practical reproductive benefits. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options due to the absence of well-defined molecular targets. Diet-induced obesity (DIO) promotes TNBC progression by reshaping systemic metabolism and inflammatory responses; however, the key circulating metabolites involved and their mechanisms remain largely unclear. This study aimed to identify key metabolites associated with TNBC progression and further investigate their biological functions and molecular mechanisms. Methods: Targeted metabolomics profiling was performed on serum samples from MMTV-PyMT spontaneous breast cancer mice to identify differential metabolites associated with DIO. Functional assays were conducted to evaluate the effects of hippuric acid on TNBC cell proliferation, migration, and invasion. RNA sequencing was conducted to explore downstream regulatory pathways, followed by validation of candidate targets using gain- and loss-of-function approaches as well as rescue experiments. Results: Hippuric acid was identified as a significantly altered metabolite in DIO conditions. Functional studies demonstrated that hippuric acid markedly inhibited the proliferation, migration, and invasion of TNBC cells, with minimal effects on non-TNBC cells. Transcriptomic analysis identified EGFL8 as a potential downstream target, which was further confirmed by qPCR and functional assays. Overexpression of EGFL8 suppressed malignant phenotypes, whereas its knockdown promoted tumor progression. Rescue experiments showed that EGFL8 partially mitigated the inhibitory effects of hippuric acid on TNBC, suggesting that it functions as an important mediator in this process. Mechanistically, hippuric acid exerted its anti-tumor effects at least in part through modulation of the EGFL8-Notch signaling axis. Conclusions: Hippuric acid suppresses TNBC progression via the EGFL8-Notch signaling pathway. These findings highlight a previously unrecognized role of a gut microbiota-derived metabolite in TNBC and suggest its potential as a therapeutic candidate, providing new prospective targets and a theoretical basis for metabolic intervention for TNBC. Full article