Search Results (668)

This study aims to investigate the effects of cysteamine zinc supplementation on milk production, composition, amino acid profile, and metabolites in mares. Building on prior experimental findings, a dose of 7 mg/kg body weight of CS-Zn was selected for the experimental group, which was compared with a control group. Milk samples were collected at various time points, and milk yield was recorded each time. Routine analysis of milk components, as well as the determination of milk metabolites and amino acids, were performed. The results indicated that, compared to the control group, the experimental group exhibited increases in milk yield and the content of milk fat, lactose, and non-fat solids (p < 0.05), with an extremely significant increase in milk protein (p < 0.01). Conversely, the levels of L-glutamine and L-proline in milk were significantly reduced (p < 0.05). Metabolomic analysis revealed that differentially expressed metabolites were enriched in pathways such as ABC transporters, D-aminoadipate metabolism, aminoacyl-tRNA biosynthesis, and protein digestion and absorption. Notably, milk metabolites including cAMp, biotin, and taurine showed a tendency to be upregulated, while oxoglutaric acid, methionine, and diacetyloxyxanthone were downregulated. Based on evidence from the literature other species, it is speculated that CS-Zn supplementation may be associated with alterations in endocrine and amino acid metabolism pathways, potentially influencing lactation performance in mares. However, because no hormones were directly measured in this study, such a mechanism remains speculative and requires direct experimental validation. Full article

Food and medicine homology (FMH) substances are increasingly utilized as nutritional and medicinal resources in sustainable livestock production. Their active ingredients include polysaccharides, flavonoids, and terpenes, which may positively affect livestock meat quality by maintaining gut microbiota homeostasis, enhancing intestinal barrier function, and facilitating nutrient absorption, as well as regulating key signaling pathways such as mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and nuclear factor-κB (NF-κB). Notably, the meat quality improvement can also be indirectly achieved via the gut–muscle axis. Gut microbiota metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and amino acid derivatives, modulate microbial homeostasis, intestinal barrier function, and nutrient absorption through the gut microbiota–metabolite axis, gut–immune axis, and nutrient absorption–signaling axis. These processes remotely regulate skeletal muscle metabolism, inflammation, and fiber type transformation, ultimately influencing meat tenderness, flavor, juiciness, and nutritional value. Despite their potential to reduce reliance on antibiotic growth promoters and enhance meat quality, multiple challenges persist, including complex component profiles, elusive mechanisms, undefined dose–effect relationships, inadequate standardization, insufficient safety evaluation and scarce direct trials on livestock meat quality endpoints. This review summarizes FMH substances that modulate the gut–muscle axis in meat quality regulation across different animal species and outlines their application prospects, aiming to facilitate antibiotic-free agriculture, the development of green functional feeds, and sustainable animal husbandry. Full article

Dietary zeaxanthin exhibits low intestinal absorption efficiency, and circulating levels are reduced in individuals with type 2 diabetes, suggesting potential metabolic relevance. However, its role during early-stage diabetes remains incompletely understood. This study examined whether dietary zeaxanthin modulates early metabolic and inflammatory responses and influences host–microbiome interactions during early T2DM progression. Four-week-old male db/db mice and wild-type C57BL/6J mice were fed an AIN-93M diet with or without 0.02% (w/w) zeaxanthin for 4 weeks. Zeaxanthin attenuated body weight gain, adiposity, hyperinsulinemia, and circulating keratinocyte-derived chemokine levels in diabetic mice. These effects were accompanied by reduced ileal membrane localization of Niemann-Pick C1-like protein 1 and decreased hepatic expression of CD36, nuclear factor kappa B p65, and phosphoenolpyruvate carboxykinase 1, without significant improvement in fasting blood glucose or hepatic triglyceride accumulation. Cecal microbiota analysis showed reduced microbial richness in diabetic mice that was not restored by zeaxanthin; however, zeaxanthin induced selective compositional shifts, including enrichment of fermentation-associated taxa (e.g., Ruminococcaceae) and normalization of Clostridium XIVb. Predicted microbial pathways related to fermentation, amino acid biosynthesis, and cofactor metabolism were also altered. Collectively, dietary zeaxanthin modulated early metabolic and inflammatory adaptation and was associated with alterations in intestinal lipid handling, inflammatory signaling, and gut microbiome composition during early T2DM progression. Full article

Preweaning piglet diarrhea not only compromises animal health but also causes significant economic losses to the swine industry; however, the underlying molecular mechanisms remain poorly understood. Here, we use a preweaning piglet model to systematically explore the underlying risk features of pre-weaning diarrhea risk through multi-omics integration analysis. We identified thousands of differentially expressed genes, proteins, and metabolites. Key findings include: (1) activation of the complement cascade but downregulation of complement receptors; (2) increased chemokine production with reduced receptor expression; (3) overexpression of mitochondrial ribosomal proteins (MRPs) and NADH: ubiquinone oxidoreductase (NDUF), suggesting mitochondrial dysfunction; (4) aberrant activation of neuroactive ligand–receptor pathways; and (5) accumulation of undigested polypeptides in the jejunum due to reduced peptidase activity and amino acid transporter expression, indicating disrupted protein digestion and absorption. These findings provide critical insights and a valuable resource for addressing the underlying mechanisms of preweaning disease challenges in newborns. Full article

Background/Objectives: Oral delivery of semaglutide (Rybelsus) relies on sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC) to enhance peptide absorption. However, formulation constraints and SNAC’s localized gastric mechanism have prompted the exploration of alternative enhancers. This study evaluated whether sodium caprate (C10), a well-characterized medium-chain fatty acid (MCFA), could achieve systemic exposure comparable to SNAC-based formulations when co-formulated in an immediate-release (IR) tablet. Methods: Preformulation studies assessed the physicochemical properties and buffering capacity of C10. Mechanistic feasibility was evaluated through Caco-2 transport studies and rat pharmacokinetic (PK) trials using aqueous suspensions, comparing the concentration-dependent effects of C10 and SNAC. Based on these findings, three IR tablet architectures (monolayer, bilayer, and dry compression-coated) were developed. The optimized formulation was evaluated in beagle dogs (14 mg semaglutide) and compared with the SNAC-based reference product. Results: C10 exhibited sufficient buffering capacity to neutralize acidic environments. In Caco-2 and rat PK studies, C10 enhanced semaglutide absorption in a concentration-dependent manner, yielding exposure levels equivalent to SNAC at matched doses. Among the tablet designs, the monolayer tablet showed the highest dissolution similarity (f₂ = 67.8) to Rybelsus. In beagle dogs, the optimized monolayer formulation produced pharmacokinetic parameters, including C_max, AUC_last, and t_1/2, that overlapped with those of the SNAC-based reference drug product under matched dosing conditions. Conclusions: These results demonstrate that C10 can effectively support oral semaglutide delivery when incorporated into a rationally designed IR tablet. The findings support the feasibility of MCFA-based permeation enhancer platforms as formulation alternatives to SNAC for oral peptide therapeutics. Full article

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. Methods: The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson’s trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Results: Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. Conclusions: These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN. Full article

Sports drinks have traditionally been formulated as carbohydrate–electrolyte beverages to support fluid replacement and energy provision during exercise. However, commercially available and experimentally tested formulations now include amino acids, proteins, phytochemicals, caffeine, menthol, ketone-related nutrients, and other functional ingredients intended to support thermoregulation, performance, or post-exercise recovery. This narrative review summarizes evidence on sports drinks and related functional beverages, with emphasis on hydration, gastric emptying and intestinal absorption, thermoregulation, biomarkers of hydration and recovery, and potential effects beyond hydration, including fatigue, muscle and organ damage, inflammation, and immune responses. Because available studies vary widely in population, exercise mode, environmental conditions, beverage composition, intake timing, and outcome measures, the evidence should be interpreted cautiously. A functional distinction is made between hydration-oriented carbohydrate–electrolyte beverages and beverages primarily designed for ergogenic or recovery-oriented purposes. Current evidence supports the practical value of appropriate fluid, electrolyte, and carbohydrate intake for maintaining hydration and exercise performance, whereas evidence for broader effects on inflammation, immunodepression, organ protection, and recovery remains context-dependent. Future studies should differentiate acute responses from longer-term adaptations, consider population-specific needs, and use standardized, context-appropriate biomarkers and ecologically valid protocols. Full article

Heavy metals in the soil inhibit plant growth, which significantly reduce the crop yield and quality. Natural Resistance-Associated Macrophage Proteins (NRAMP) are widely distributed on the plasma and vacuolar membranes of plant roots, stems, and leaves. The NRAMP gene family plays a crucial role in modulating plant heavy-metal uptake, sequestration, distribution, and translocation, while the molecular evolution and mechanisms underlying these processes remain unclear. Here, we reviewed recent progress on plant NRAMP genes, focusing on their structural characteristics and functions in the absorption, transport, accumulation, and detoxification of various heavy metals. Furthermore, we performed an evolutionary analysis of NRAMP in green plants, indicating expansion and tandem duplication in ferns. In addition, their key amino acid sequences and secondary structures were highly conserved across plant species. The expression of diverse tissue showed that NRAMP genes displayed distinct spatial regulation in the leaves and roots. We also explored the underlying molecular mechanisms and regulatory pathways by which NRAMP genes influence heavy metal uptake. Therefore, by integrating structural conservation, molecular evolution, tissue- and single-cell expression patterns, ion-stress-responsive expression, regulatory pathways, and the Cd–Mn nutrient–toxin trade-off, this review provides a framework for identifying unresolved NRAMP functions and for guiding future strategies in low-heavy-metal crop breeding, metal homeostasis engineering, and phytoremediation. Full article

N-carbamylglutamate (NCG) is a structural analog of N-acetylglutamate and has multifunctional roles in animal production. However, few studies have been conducted to evaluate the effects of NCG on protein digestive function and muscle growth in broiler chickens. This study investigated whether NCG could improve muscle growth via protein digestive ability and amino acid metabolism in broiler chickens. A total of 144 one-day-old male broiler chickens were randomly allocated to four treatments with six replicates of 6 broiler chickens each. The treatments were a basal diet and a basal diet with NCG supplementation at three graded levels (150 g/t, 300 g/t, and 450 g/t of NCG). The results showed that NCG supplementation significantly improved the average daily weight gain (ADG) and decreased the feed conversion ratio (FCR) compared to the control group (p < 0.05) and increased the weight of leg muscle and breast muscle. Furthermore, NCG supplementation significantly increased protein digestibility, the activities of amylase, trypsin and lipase, and villus height in the ileum (p < 0.05), which demonstrated that digestibility and absorption were improved by NCG in broiler chickens. Analysis of plasma amino acids, hormone levels and the gene expression of breast muscle revealed that NCG increased the concentration of GABA, glutamate, glutamine, leucine, threonine, valine, branched-chain amino acids and essential amino acids and the levels of testosterone and IGF-1 in plasma (p < 0.05). Additionally, NCG increased the expression of mTOR and P70S6K in breast muscle tissue. Therefore, NCG supplementation could be an important nutritional strategy to improve product performance, muscle growth and development, and meat yield. The 300 g/t supplementation level was found to be the practical optimum dose, as it produced effects comparable to the highest dose (450 g/t) on most parameters while offering better cost-effectiveness. This study provides new insights into the application of NCG for meat production improvement in broiler chickens. Full article

Background/Objectives: Global population aging is associated with a rising prevalence of malnutrition among adults aged ≥80 years. Gut dysbiosis is linked to immune decline and impaired nutrient absorption, and aerobic exercise may enhance microbial diversity. This study investigated gut microbiota changes after a 12-week aerobic exercise intervention in octogenarians stratified by nutritional status. Methods: A total of 129 nursing home residents (≥80 years) were classified via the Mini Nutritional Assessment Short-Form (MNA-SF) into a healthy group (HG, MNA-SF ≥ 11) and a malnourished group (MG, MNA-SF < 11). Both groups underwent a 12-week brisk walking intervention (three sessions/week, 1 h/session, 40–60% heart rate reserve). Fecal samples were collected at baseline and post-intervention and were analyzed via shotgun metagenomic sequencing. Results: A total of 36 participants completed the intervention (HG = 17, MG = 19). Within-group baseline-to-post-intervention analysis showed no significant changes in alpha or beta diversity in the MG. However, post-intervention between-group comparison revealed higher microbial richness and diversity in the MG vs. the HG, with enrichment of taxa including Faecalibacterium prausnitzii and Streptococcus salivarius. Functional analysis revealed significant enhancements in metabolic pathways related to amino acid biosynthesis, protein synthesis, and quorum sensing in the MG. In contrast, the HG showed limited shifts in microbial diversity but an increase in species involved in carbohydrate metabolism. Conclusions: After 12 weeks, the malnourished group showed higher post-intervention microbial richness and diversity than the healthy group, with differences in taxonomic and predicted functional profiles. Without a non-intervention control group, the microbiota differences observed during the 12-week aerobic exercise period can only be considered observational associations, not causal. Additionally, the high dropout rate (72.1%) limits the generalizability of the findings. Clinical trial registration: The Chinese Clinical Trial Registry on 19 October 2022 (ChiCTR2200064801). Full article

Caffeic acid (CA), a catechol-containing phenolic acid, is readily oxidized to its quinone form during food processing and can form covalent adducts with amino acid residues in proteins. This study aimed to detect the presence of caffeic acid–cysteine adduct (CA-Cys) in meat products supplemented with dandelion extract, and further investigate its antioxidant properties and intestinal absorption characteristics. Compared with CA, CA-Cys exhibited stronger ABTS radical scavenging activity, greater ferric-ion reducing capability, and lower cytotoxicity in cultured cells. In the oxidative stress model induced by hydrogen peroxide (H₂O₂) in Caco-2 cells, CA-Cys treatment enhanced antioxidant enzyme activities in a dose-dependent manner. In the Caco-2 cell monolayer model, the apparent permeability coefficient and cellular uptake of CA-Cys were 4.32 × 10⁻⁵ cm/s and 0.85 ± 0.14 nmol/mg protein, respectively. These values were approximately 1.23-fold and 1.67-fold higher than those of CA, suggesting that CA-Cys may have significant advantages in intestinal absorption. These results indicate that adducts represent potentially beneficial substances for green food processing. Full article

Metabolic changes in saliva are known to be closely associated with the presence of non-oral cancers, particularly breast cancer. The diagnostic and prognostic potential of salivary biomarkers in breast cancer has been demonstrated, but their applicability for assessing therapy response has not yet been established. The aim of this study was to comprehensively analyze clinical, pathological, molecular, and salivary characteristics when assessing the response to neoadjuvant chemotherapy for breast cancer. The study included 361 breast cancer patients undergoing their first course of chemotherapy and 127 healthy volunteers without breast pathologies. Saliva samples were collected from all volunteers before treatment. Saliva analysis results for amino acids, lipids, and tumor markers were compared with tumor pathomorphism assessment after breast cancer surgery. The proportion of patients with a complete response to therapy was statistically significantly lower after menopause, and in those with HER2-negative breast cancer, moderate tumor differentiation, and high estrogen and progesterone receptor expression. For the first time, a body mass index (BMI) greater than 25 and low HER2 expression (HER2-low) were shown to have an unfavorable prognosis. The criterion for selecting informative salivary metabolites was a multidirectional change in minimal and complete pathological responses to therapy compared to healthy controls. Thus, prognostically favorable signs were a decrease in the concentration of urea below 7.5 mmol/L (OR = 1.921; 95% CI 1.061–4.270; p = 0.0342), a decrease in the area of the absorption band at 2957 cm⁻¹ below 24 (OR = 3.875; 95% CI 1.160–12.70; p = 0.0003), and an increase in the concentration of cancer antigen CA27.29 above 3 U/L (OR = 2.138; 95% CI 1.021–7.273; p = 0.0343) and CA-15-3 above 39 U/L (OR = 3.896; 95% CI 1.062–14.07; p = 0.0072). With a simultaneous increase in both CA27.29 and CA15-3, the probability of a complete response to therapy increased (OR = 4.288; 95% CI 1.056–17.09; p = 0.0013). Multivariate analysis showed that an independent prognostic indicator, along with the expression status of HER2, estrogen receptors, differentiation degree, BMI, and menopause status, was the concentration of CA15-3 in saliva (AUC = 0.789, 95% CI: 0.737–0.842, p = 0.0001). Identifying new markers will help physicians formulate treatment plans tailored to a patient’s individual risk factors, leading to increased survival and improved quality of life. Full article

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

Background: Nitrous oxide (N₂O) is increasingly used as a recreational drug, leading to neurological and systemic toxicities. However, due to the rapid elimination and minimal alteration of nitrogen oxides, the short direct detection window complicates the assessment of N₂O exposure. Method: In this study, we investigated the effects of chronic N₂O exposure on plasma metabolites using an untargeted metabolomics approach in a mouse model. C57BL/6 mice were exposed to 90,000 ppm N₂O (1 h, twice daily for 28 days) or room air. Plasma samples were analyzed via UHPLC -Triple TOF -MS. Orthogonal partial least squares discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) curves were used to identify differential metabolites. Result: A total of 35 differential metabolites were identified. Eight metabolites with an area under the curve (AUC) > 0.90 were selected as candidate biomarkers, including up-regulated SOPC and PC(16:0/16:0) (suggesting disrupted phospholipid remodeling and membrane integrity), and down-regulated DL-tryptophan, creatine, ectoine, indole, His-Ser, and Ile-Pro. Pathway enrichment analysis revealed significant alterations in glycine, serine and threonine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; protein digestion and absorption; and tryptophan metabolism. Conclusions: Our data indicate that chronic N₂O exposure disrupts multiple amino acid-related metabolic pathways (e.g., tryptophan-kynurenine pathway) and phospholipid homeostasis. The identified metabolite changes, along with vitamin B₁₂, homocysteine, and methylmalonic acid, may constitute a specific metabolic fingerprint for N₂O exposure. These findings help reveal the intrinsic mechanistic links underlying metabolic disorders induced by N₂O exposure. Full article

The hybrid sturgeon (HS, Acipenser baerii Brandt ♀ × A. schrenckii Brandt ♂) was compared with its parental varieties (Siberian sturgeon (SS) and Amur sturgeon (AS)) to evaluate muscle quality differences. Three sturgeon species were bred from the same batch, reared under identical conditions until three years of age, and then male fish from each species (AS, 3.2 ± 0.18 kg; SS, 2.5 ± 0.14 kg; HS, 3.5 ± 0.21 kg) were sampled for analysis of muscle nutritional composition, texture, microstructure, and metabolomics. Results showed no significant differences in proximate composition, hydrolyzed amino acids, pH, or water-holding capacity among the three groups. However, HS exhibited higher gumminess and chewiness than both parent species, as well as greater hardness and springiness compared with the SS. Muscle fiber density was higher in HS than in the AS, but no significant difference was observed between HS and SS. Levels of free amino acids (Val, Ile, Ala) were lower in HS than in AS. In terms of fatty acid profiles, HS showed elevated polyunsaturated fatty acids compared with SS, resembling the pattern observed in AS. Muscle color of HS was similar to that of SS, whereas its a* value differed from those of AS. Metabolomics identified differential metabolites (GABA, D-glucosaminic acid, AP4) enriched in pathways such as ABC transporters, protein digestion and absorption, and amino acid metabolism. Overall, HS combines improved texture traits with meat quality attributes resembling SS (muscle color, free amino acids) and AS (polyunsaturated fatty acids). These characteristics suggest that HS possesses a distinctive combination of meat quality traits. Full article