Search Results (1,872)

Background: This study investigates metabolic perturbations in serum samples associated with different genotypes (AA, AC, and CC) of the schizophrenia susceptibility gene NOS1AP-rs12742393. Methods: Publicly available datasets acquired using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–QTOFMS) were analyzed by employing network and enrichment approaches. Results: Key metabolites, including tryptophan, 2-aminobutyric acid, palmitic acid, and 5-hydroxytryptophan, were strongly linked to metabolic networks in genotypes AA-AC and AA. Enrichment analysis was conducted to identify metabolite sets differentially distributed across these genotypes, with a particular focus on genotype AA. Conclusions: The findings suggest that NOS1AP-rs12742393 contributes to complex metabolic alterations involving amino acids, organic compounds, fatty acids, and cholic acids. Moreover, serum metabolome analysis demonstrates sufficient sensitivity and specificity to provide insights into NOS1AP-rs12742393 genotype-associated metabolic profiles, supporting a network-based approach to understanding schizophrenia susceptibility. Full article

Background/Objectives: This study investigated the correlation of oxidative stress biomarkers with the activity of idiopathic nephrotic syndrome (INS) in Slovenian children. Methods: In this prospective study, sequential plasma and urine samples from 20 children with INS in different phases of disease activity were taken: at first disease presentation or relapse (before glucocorticoid (GC) treatment), at time of remission achievement, and after discontinuation of GC treatment. This study measured oxidative stress biomarkers, such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), hexanoyl-lysine (HEL) adduct, dityrosine (DiY), and 15-isoprostane F2t, using competitive enzyme-linked immunosorbent assay (ELISA) and assessed oxidative status using the FRAS 5 analytical system, which enables rapid photometric measurement of both oxidative and antioxidant capacity from biological fluids. Two complementary tests were performed: the d-ROMs test (derivatives of reactive oxygen metabolites) and the PAT (plasma antioxidant test). The oxidative stress index (OSI) was calculated as the ratio between them. Results: Concentrations of isoprostanes in urine were statistically significantly lower in patients at first disease presentation or relapse compared to time of remission achievement. Values of PAT test in serum were significantly highest after GC treatment. Values of d-ROMs test in serum were significantly lower at time of remission achievement compared to first disease presentation or relapse. Values of 8-OHdG, HEL, DiY (in plasma and urine), isoprostanes, and OSI in plasma did not statistically significantly differ in various phases of disease activity. Conclusions: Isoprostanes in urine and PAT in serum could serve as potential biomarkers of oxidative stress and disease activity in children with INS. Full article

This study investigates the effect of walnut green husk extract (WE) on gut microbiota, metabolites, and immune-antioxidant changes in fattening pigs through gut microbiota-metabolite interactions. A total of 60 healthy fattening pigs (Duroc × Landrace × Yorkshire) with an initial body weight of 65.2 ± 3.1 kg were randomly assigned to two groups (n = 30 per group): the control group (NC), which was fed a basal diet, and the WE group, which was fed the basal diet supplemented with 0.1% walnut green husk extract (WE). Dietary supplementation with 0.1% WE significantly increased the relative abundances of beneficial bacteria (e.g., Firmicutes, Lactobacillus) and reduced pathogenic bacteria (e.g., Proteobacteria, Shigella). Untargeted metabolomics identified 170 differentially accumulated metabolites, among which propionic acid—a key short-chain fatty acid with immunomodulatory effects—was significantly upregulated by 1.09-fold (p = 0.03) and showed a positive correlation with beneficial microbial abundances. These metabolites were enriched in glycerophospholipid and α-linolenic acid metabolism pathways, where eicosadienoic acid inhibited the nuclear factor kappa-B (NF-κB) pathway for anti-inflammatory effects, and methyl cinnamate synergistically regulated mitogen-activated protein kinase (MAPK) signaling with Lactobacillus. Serum analyses showed that WE significantly enhanced IgA, IgM, and IgG levels by 3.97-fold, 4.67-fold, and 4.43-fold (p < 0.01), reduced malondialdehyde (MDA) concentration by 82.8% (p < 0.01), and trended to improve antioxidant capacity via glutamine. Mechanistically, WE promoted short-chain fatty acid production by beneficial bacteria, forming a “microbiota–metabolite–immunity” cascade to enhance lipid metabolism and alleviate intestinal inflammation. These findings highlight that WE provides multi-omics evidence for its application as a functional feed additive. Full article

Background/Objectives: Genetic variation has been thought to alter the human dietary requirement for choline and subsequent circulating levels of its metabolites betaine and dimethylglycine (DMG). The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) associated with serum choline, betaine, and dimethylglycine (DMG) as well as choline-to-betaine and betaine-to-DMG ratios. Methods: Data from the Collaborative Study of Genes, Nutrients and Metabolites (CSGNM; n = 2402) were used to model individual associations of choline, betaine, and DMG circulating metabolites and their ratios with 680,975 SNPs, using linear regression. Models were unadjusted (model 1), adjusted for age and sex (model 2), and further adjusted for selected principal components (model 3) and B₁₂, B₉, B₆, and holotranscobalamin (model 4). Statistical significance was set at p < 5.0 × 10⁻⁵. Affected SNPs in the dbSNP (database of Single Nucleotide Polymorphisms) were then identified. Results: GWAS revealed both intuitive and novel results, including the recently described SLC25A48, several intronic variants in the gene encoding LYPLAL1, and a pair of SNPs present in the intronic region of PID1 related to serum choline. SNPs related to betaine and DMG included SLCA12, BHMT, DMGDH, and additional SLC family transporters that require further validation. While exploratory, GWAS of the choline-to-betaine and betaine-to-DMG ratios revealed common targets with direct links to choline and one-carbon metabolism. Conclusions: These results suggest that metabolic handling of choline has genetic determinants not formerly recognized in the scientific literature. Replication is needed in larger cohorts due to low statistical power. Full article

Mastitis is a common disease for dairy cows that exerts tremendously detrimental impacts on the productivity of cows and economic viability of pasture. Dihydromyricetin (DMY) is a flavonoid monomeric compound that possesses anti-inflammatory and antioxidant activity. This study aimed at dissecting the effects of DMY on the lactation performance, blood parameters, gut microbiota, and metabolite profiles of dairy cows with subclinical mastitis (SM). The results showed that dietary supplementation with DMY resulted in a reduction in milk somatic cell count, an increase in serum T-AOC and CAT activity, as well as a decrease in serum MDA content. DMY significantly enhanced the prevalence of Coprococcus and Roseburia and reduced the proportion of Cyanobacteria, Proteobacteria, and Dehalobacterium. The amino acid degradation, antibiotic resistance, and O-antigen building blocks biosynthesis (E. coli) capacity of gut microbes were notably diminished by DMY supplementation in cows with SM. Moreover, fecal and plasma metabolomic analysis revealed that DMY intervention reduced the abundance of pro-inflammatory metabolites including arachidonic acid analogues, ω-6 PUFA, and structural components of bacteria. Nevertheless, the levels of anti-inflammatory and antioxidant metabolites involving secondary bile acids, antioxidant vitamins, specific amino acid analogues, etc. were elevated by DMY administration. Overall, DMY might ameliorate SM via enhancing antioxidant capacity and improving the structure of the hindgut microbial community and metabolite profiles in dairy cows. These findings underscore the potential of DMY as a valuable dietary supplement for the improvement of mammary inflammatory diseases in dairy cows. Full article

Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing radiation. Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models. Previously, we have demonstrated that GT3 has radioprotective efficacy in intestinal epithelial and crypt cells, and restores transcriptomic changes in NHPs with a supralethal dose of 12 Gy total-body irradiation (TBI). Methods: In this study, we evaluated the effect of 12 Gy partial-body irradiation (PBI) or TBI on metabolomic changes in serum samples and the extent to which GT3 was able to modulate these irradiation-induced changes. A total of 32 nonhuman primates were used for this study, and blood sample were collected 3 days (d) prior to irradiation, and 4 hours (h), 8 h, 12 h, 1 d, 2, and 6 d post-irradiation. Results: Our results demonstrate that exposure to a supralethal dose of radiation induces a complex range of metabolomic shifts with similar degrees of dysregulation in both partial- and total-body irradiated animals. The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. Conclusions: GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points. Full article

This study evaluated dietary inclusion of tannin-based feed additives on heifer performance and physiological measures associated with fescue toxicosis and vaccine response. Forty-five yearling beef heifers (292.6 ± 29.0 kg) grazing toxic, endophyte-infected (E+) tall fescue pastures were assigned to 1 of 3 treatment groups: (1) soybean hulls (SH; n = 3 pastures), (2) SH and BX tannin-saponin additive (BX; 10.0 g heifer⁻¹ d⁻¹; n = 3 pastures), and (3) SH and ATX tannin-polyphenol additive (ATX; 5.0 g heifer⁻¹ d⁻¹; n = 3 pastures). Treatments were administered over an 84 d period. Data were analyzed using R and SAS 9.4 with treatment as a fixed effect, block as a random effect, and pasture as the experimental unit. Treatment effects were assessed at the pasture level. Average daily gain (ADG) of heifers receiving ATX (0.53 kg/d) and BX (0.49 kg/d) were increased relative to heifers receiving SH only (0.23 kg/d) between D56 and D84 (p = 0.07). There was no impact of treatment on other performance measures (p > 0.15) or on serum metabolite responses including bovine herpesvirus type 1 (BHV-1) titers (p > 0.15), prolactin (p = 0.97), haptoglobin (p = 0.26), and blood urea nitrogen (BUN; p = 0.38). Preliminary results show the potential for improved weight gain, suggesting further investigation with more experimental units is warranted. Full article

Background/Objectives: Fat-free mass (FFM) loss after metabolic and bariatric surgery (MBS) is associated with adverse long-term outcomes, including osteoporosis. Identifying biomarkers that predict excessive FFM loss can improve perioperative patient management and postoperative risk stratification. This study investigated whether preoperative amino acid metabolite (AAM) levels could predict excessive FFM loss after laparoscopic sleeve gastrectomy (LSG). Methods: Forty patients with morbid obesity who underwent LSG between 2019 and 2020 were retrospectively analyzed. Based on the FFM loss to body weight loss ratio (%FFML/BWL) at 3 months postoperatively, patients were categorized into excessive (>25%) and non-excessive (≤25%) FFM loss groups. Anthropometric measurements and serum sampling were performed preoperatively and at 3, 6, and 12 months postoperatively. AAM profiles were collected before surgery. Statistical analyses, including logistic regression and receiver operating characteristic curves, were performed. Results: Twenty-five patients showed excessive FFM loss 3 months after surgery. They had significantly lower preoperative tyrosine (Tyr) levels (p = 0.025). Logistic regression revealed that higher Tyr levels were significantly associated with lower odds of being male, suggesting a potential protective effect (odds ratio (OR) =0.019, p = 0.010). Tyr profiling demonstrated acceptable predictive performance (area under the curve =0.715, p = 0.025). Despite nonsignificant p-values, trends showed lower FFM and muscle mass and higher fat mass in the excessive FFM loss group throughout follow-up. Conclusions: Preoperative Tyr profiling may help identify patients at risk for excessive FFM loss. These findings support prioritizing metabolic health alongside total weight loss in the evaluation of MBS outcomes. Full article

Polystyrene nanoplastics (NPs) threaten agricultural ecosystems and the food chain; however, their hepatotoxicity in chickens, a key poultry species, remains unclear. This study investigated the effects of chronic NP exposure on hepatic metabolism to evaluate food safety risks in poultry products. Chickens were orally exposed to 100 nm polystyrene NPs via feed for 120 days. Histopathological evaluation, serum biochemical analysis revealed hepatotoxicity in NP-exposed poultry, characterized by histopathological liver injury, elevated lipid droplet accumulation, significantly increased alanine aminotransferase (ALT) activity, and elevated triglyceride (TG) levels (p < 0.05). Untargeted LC-MS/MS Metabolomics profiling identified 193 differentially abundant metabolites—predominantly organic acids and lipids—with L-leucine and NADH emerging as pivotal metabolic hubs. A KEGG pathway analysis demonstrated significant enrichment in purine metabolism and oxidative phosphorylation, while a gene set enrichment analysis (GSEA) confirmed the suppression of ABC transporters. Notably, the key biomarkers 9-cis-retinal and phenylalanyl phenylalanine were significantly altered, reflecting metabolic disturbances linked to NPs exposure. Overall, this study characterized exposure-associated metabolic signatures and established NP-induced hepatic injury phenotypes in poultry production systems. Full article

Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved mechanisms. Mice were treated with Uro-B (50 and 100 mg/kg) for four days and received ANIT (75 mg/kg) once on the second day. Our data revealed that Uro-B reduced elevated serum transaminases, alkaline phosphatase, lactate dehydrogenase, and total bilirubin levels associated with ANIT injection. Histopathologically, Uro-B effectively ameliorated ANIT-induced disruption of the hepatic architecture as represented by repressed necro-inflammation and bile duct proliferation. Uro-B also maintained oxidant/antioxidant status that was dysregulated by ANIT. Mechanistically, Uro-B markedly activated Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling with subsequent upregulation of hepatic heme oxygenase-1 expression. On the other hand, Uro-B suppressed the ANIT-induced expression of nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Interestingly, Uro-B repressed peroxisome proliferator-activated receptor alpha (PPARα) expression in the liver. These findings indicate a promising hepatoprotective effect of Uro-B against ANIT-induced CLI in mice. Uro-B modulated the interplay between Keap1/Nrf2, NF-κB/TNF-α, and PPARα signaling pathways, resulting in powerful antioxidant and anti-inflammatory effects. Full article

First-line treatment for localized prostate cancer (PCa) includes radical prostatectomy (RP) for high-risk disease. However, in many cases, patients experience biochemical recurrence (BCR), heralded by rising prostate specific antigen (PSA) levels in the serum. Our goal was to identify metabolic pathways that are disrupted in BCR to determine potential targets of therapy. We conducted metabolomic analysis in prostate tissue from the tumors of 74 patients who underwent prostatectomy as treatment for localized PCa and correlated levels of metabolites with clinical and non-clinical factors. Cholesterol and triglycerides were upregulated in Hispanic vs. non-Hispanic and in obese vs. non-obese individuals, respectively. Both lipids and non-lipids were altered with increasing Gleason grades and clinical stages. High post-RP PSA (>0.1 ng/mL) indicated recurrence (p = 0.0094) and correlated with alterations in 141 metabolites including 114 lipids and 26 non-lipid molecules. The largest increase with high post-RP PSA was in 2-hydroxyglutaric acid (2-HG), a product of the tricarboxylic acid (TCA) cycle, that had previously been established as an oncometabolite in other cancers. 2-HG was highly selective and specific for high post-RP PSA (AUC = 0.8526; p = 0.0002) while Kaplan–Meier curves indicated that among patients who recurred, high 2-HG in the tumor reduced time-to-recurrence from 84 months (for those with low 2-HG) to 38 months (for those with high 2-HG). The addition of D2HG, an enantiomer of 2-HG, increased the growth rate of LNCaP and C4 cells, and also increased Akt and ERK phosphorylation. 2-HG is upregulated in PCa tumors from patients who experience high post-RP PSA indicative of recurrence. Future studies may target this metabolite to prevent recurrent disease. Full article

Aflatoxin B1 (AFB1) is a highly toxic secondary metabolite produced by Aspergillus species. Its extensive contamination of animal feed and human food poses significant health hazards to livestock and humans, with hepatotoxicity being a primary concern. This study investigated the protective effect of baicalin on AFB1-induced liver injury in ducklings. In the first experiment, ducklings were administered AFB1 at doses of 0, 6, 12, or 24 μg/kg body weight/day for 7 days to identify the optimal concentration for establishing a model of AFB1-induced growth performance and liver injury. Administration of AFB1, particularly at the higher doses (12 and 24 μg/kg body weight/day), significantly reduced growth performance and induced structural and functional liver injury (p < 0.05). In a second experiment, ducklings were administered AFB1 (12 μg/kg body weight/day) with or without baicalin (25–100 mg/kg body weight/day) for 7 days. Dietary baicalin significantly increased the serum albumin level; reduced the serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels; improved growth performance; and ameliorated structural and functional liver injury in ducklings exposed to AFB1 (p < 0.05). The results indicate that dietary baicalin alleviates AFB1-induced liver injury and growth performance decline in ducklings. Hence, baicalin could serve as a potential feed additive to reduce the harmful effects of AFB1 in the poultry breeding industry. Full article

Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 10¹⁰ cells/human/day), low-dose live NB23 (1 × 10¹⁰ CFUs/human/day), or high-dose live NB23 (3 × 10¹⁰ CFUs/human/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study. 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

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article