PubMed

Cell Death Dis. 2025 May 15;16(1):381. doi: 10.1038/s41419-025-07699-6.ABSTRACTObesity is accompanied with accumulation and pro-inflammatory polarization of macrophages in adipose tissue (AT), leading to systematical inflammation and insulin resistance. Impaired lipid metabolism and endocrine function in adipocytes is recognized as a culprit in the onset of adipose tissue inflammation. Lipid levels can be managed via inhibiting both synthesis and transport or via increasing fatty acid oxidation (FAO). The deacetylase Sirtuin 3 (SIRT3) participates in inflammatory responses via regulating mitochondrial function and FAO. Herein, an AT-specific SIRT3 overexpression mice model (AT-SIRT3OE) was generated using adeno-associated virus transduction. AT-specific SIRT3 overexpression did not alter body weight or adiposity in either regular chow diet or high-fat diet (HFD) fed mice. AT-SIRT3OE mice exhibited improved insulin sensitivity in HFD-fed mice, through alleviating infiltration of macrophage and pro-inflammatory macrophage polarization in the epididymal AT. The metabolomics analysis indicated that SIRT3 overexpressed adipocytes accumulated more L-carnitine (LC) and less long-chain acylarnitines in the medium. Furthermore, SIRT3 directly deacetylates and activates carnitine palmitoyltransferase 2 (CPT2), an obligate step in mitochondrial long-chain FAO, to enhance the LC turnover pool in adipocytes, which in turn promoted lipid metabolism and anti-inflammatory polarization in macrophages. Collectively, our study provided new evidence that adipocyte-expressed SIRT3 alleviates inflammatory crosstalk between adipocytes and macrophages through manipulating LC pool. Activating SIRT3 in adipocytes could be a potential strategy to alleviate obesity-related metabolic diseases.PMID:40368890 | DOI:10.1038/s41419-025-07699-6

J Agric Food Chem. 2025 May 14. doi: 10.1021/acs.jafc.5c02897. Online ahead of print.ABSTRACTAs a part of a continuous 90 day subchronic toxicology study, integrated metabolomic and transcriptomic approaches were applied to assess the metabolic network changes in the livers of Kunming mice exposed to three typical thermally induced food toxicants, including oxidative derivatives of triacylglycerols (ox-TGs), aldehydes, and 3-monochloropropane-1,2-diol esters (3-MCPDE), as well as their mixtures. Results showed lipid metabolic dysregulation through impaired purine metabolism, PPAR signaling, and bile acid metabolism. Ox-TGs emerged as the most hazardous compound, altering over 10 genes/enzymes. 3-MCPDE exhibited gender-specific effects, significantly upregulating fatty acid metabolism and gluconeogenesis genes in males. Interestingly, toxicant mixtures attenuated the adverse metabolic effects caused by individual compounds, demonstrating complex regulatory mechanisms in fatty acid biosynthesis and oxidation. The metabolomic and transcriptomic analyses conducted in this study revealed that combined exposure to multiple toxicants generated during lipid thermal processing may induce more complex toxicity effects than the simple additive effects of individual toxicants. Certain antagonistic effects were observed when comparing individual toxicants to their mixtures, highlighting the need for further mechanistic verifications in this area.PMID:40368873 | DOI:10.1021/acs.jafc.5c02897

Trends Endocrinol Metab. 2025 May 13:S1043-2760(25)00083-9. doi: 10.1016/j.tem.2025.04.008. Online ahead of print.ABSTRACTBreast cancer (BC) remains the most prevalent malignancy among women worldwide. While genetic predisposition and reproductive history are key contributors to its development, modifiable risk factors are also important, particularly those linked to lifestyle behaviors, often influencing the endogenous metabolome. Over the past decade, mass spectrometry-based metabolomics has enabled agnostic investigations into correlations between the metabolome and BC risk. Here we review recent results from prospective nested case-control studies, which have led to the identification of significantly different metabolites between women who subsequently developed BC and those who did not. As replication of these findings remains limited, we emphasize the need for robust quantitative validation studies, cancer subtype-specific analyses in diverse populations, and expanded chemical space coverage of analytical assays.PMID:40368707 | DOI:10.1016/j.tem.2025.04.008

Trends Immunol. 2025 May 13:S1471-4906(25)00120-6. doi: 10.1016/j.it.2025.04.007. Online ahead of print.ABSTRACTRecently, Kondo et al. engineered the coexpression of a T cell receptor (TCR) and a chimeric antigen receptor (CAR) and developed an antagonism-enforced braking system where TCR signals both enhance and inhibit CAR activation. This work may enable rational design of CAR-T agents that limit toxicity to healthy tissue.PMID:40368698 | DOI:10.1016/j.it.2025.04.007

J Dermatol Sci. 2025 Apr 24:S0923-1811(25)00067-2. doi: 10.1016/j.jdermsci.2025.04.011. Online ahead of print.ABSTRACTBACKGROUND: Vitiligo is a depigmentation disorder frequently associated with emotional distress; however, the precise mechanisms underlying this co-morbidity remain unclear.OBJECTIVE: This study aims to investigate whether gut dysbiosis and gut metabolites contributes to emotional distress in patients with vitiligo.METHODS: Depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Totally enrolled 28 vitiligo patients were diagnosed with depression or anxiety (VWD), 44 without such conditions (VTD), and 37 healthy controls (HC). Stool samples were analyzed using 16S rRNA gene sequencing and liquid chromatography triple quadrupole tandem mass spectrometry.RESULTS: The intestinal flora of VWD group changed significantly with reduced α-diversity. The β-diversity varied among groups. Megasphaera and Anaerostipes increased in the VWD group, whereas Bilophila etc. decreased. Linear Discriminant Analysis Effect Size revealed Lachnoclostridium as a representative flora in the VWD and Faecalibacterium as a representative flora in the VTD. Metabolites such as L-glutamic acid and indole were lower in the VWD group than in the HC, while oleamide, cuminaldehyde, and taurine were higher in the VWD with VTD group. Lachnoclostridium negatively correlated with indole and L-glutamic acid. This study identified notable variations in pathways involved in the biosynthesis of phenylalanine, tyrosine, and tryptophan bile secretion, GABAergic synapses, and taurine and hypotaurine metabolism between the VWD and HC groups.CONCLUSION: Specific fecal microbes and metabolites may contribute to the pathogenesis of VWD. These findings provide a novel perspective for addressing emotional distress in patients with vitiligo by targeting the gut-brain-skin axis.PMID:40368677 | DOI:10.1016/j.jdermsci.2025.04.011

J Nutr. 2025 May 12:S0022-3166(25)00290-1. doi: 10.1016/j.tjnut.2025.05.008. Online ahead of print.ABSTRACTBACKGROUND: Bile acids are essential molecules that facilitate lipid emulsification and function as signaling molecules mediating host-microbiota interactions. They shape the gut microbial structure and function, playing a critical role in metabolic regulation via the gut-liver axis.OBJECTIVES: This study aimed to investigate the effects of exogenous bile acids, primarily hyocholic acid (HCA), on the microbiota-gut-liver metabolism in male Tan-lambs fed a high-grain diet.METHOD: Thirty six-month-old male Tan lambs (Ovis aries) were randomly allocated into either a control (CON) group or an HCA-supplemented group (n = 15 per group). The trial lasted 84 days, including a 14-day adaptation period. On day 70, six lambs from each group were randomly selected for slaughter. Rumen and ileal contents were collected for microbial profiling via 16S rRNA sequencing, and liver tissue samples were harvested for transcriptomic and metabolomic analyses.RESULTS: The HCA intervention significant altered the composition and structure of ruminal and ileal bacteria. Notable increases were observed in Turicibacter (linear discriminant analysis (LDA) score = 2.48; P < 0.05) and Muribaculaceae (LDA score = 3.75; P < 0.05) in the rumen, and Eubacterium fissicatena group (LDA score = 2.50; P < 0.05) in the ileum. Key hepatic genes and metabolites targeted by HCA were identified, including ENPP3, RFK, Ifi203, LIPG, CYP1A1, CYP4A11, nordeoxycholic acid (log-fold change = 6.30, P < 0.005), α-muricholic acid (log-fold change = 5.60, P < 0.001), β-muricholic acid (log-fold change = 5.60, P < 0.001).CONCLUSIONS: Exogenous bile acids regulate the microbiota-gut-liver axis, influencing hepatic glycolipid metabolism in sheep. Specifically, nordeoxycholic acid, demonstrates potential as a dietary intervention to promote metabolic homeostasis in ruminants. These findings highlight the potential of HCA and norDCA as functional feed additives or prebiotic agents for improving metabolic health in ruminants and potentially other species.PMID:40368303 | DOI:10.1016/j.tjnut.2025.05.008

Fitoterapia. 2025 May 12:106618. doi: 10.1016/j.fitote.2025.106618. Online ahead of print.ABSTRACTArisaema cum Bile (DNX, Dan Nanxing) is a traditional fermented Chinese medicine renowned for its antipyretic properties. Conventionally, DNX is produced through natural fermentation using indigenous microbial strains, which often results in an unstable microbial composition and susceptibility to contamination by harmful microorganisms. Additionally, inconsistencies in the fermentation process and outdated quality control methods further compromise the quality and safety of the final product. This study aimed to investigate the production of DNX using isolated fungal combinations under controlled conditions. Based on separation and high-throughput sequencing analyses, four dominant fungi were selected for restricted fermentation. When inoculated at a ratio of 1:1:2:2, the amylase activity of DNX reached its peak, with fermentation endpoints determined by both amylase activity and changes in calcium oxalate crystal structure. Metabolomic analysis revealed that among the top 30 compounds with the highest content, 24 exhibited consistent relative content changes between restricted fermentation and natural fermentation. In febrile mice, DNX produced by both fermentation methods demonstrated comparable antipyretic effects, significantly reducing body temperature and inflammatory cytokines (p < 0.05), including IL-6 and TNF-α, to normal levels. Furthermore, inflammation-related signaling pathways, such as cAMP and PGE2 levels, were significantly downregulated following DNX treatment (p < 0.01). These findings suggest that DNX produced through restricted fermentation exhibits therapeutic effects comparable to those achieved by natural fermentation. This study proposes a novel fermentation strategy for the industrial production of DNX, offering improved consistency and quality control.PMID:40368064 | DOI:10.1016/j.fitote.2025.106618

J Environ Manage. 2025 May 13;386:125702. doi: 10.1016/j.jenvman.2025.125702. Online ahead of print.ABSTRACTSulfonamide residues in soil have the potential to affect soil microbial community and promote the dissemination of antibiotic resistance. Biochar is a strong candidate for soil enhancement, however, its feasibility and mechanisms in controlling the burden of antibiotic resistance and restoring soil quality under antibiotic contamination require systematic evaluation. Thus, a pot experiment using Anthrosol soil amended with 3 % woody biochar was conducted to evaluate the efficacy in mitigating the inhibition of plant growth, antibiotic resistance genes (ARGs) proliferation, and microbial community disruption at an environmentally relevant (feedlot-adjacent soil equivalence) and a tenfold elevated concentration. Results showed that biochar effectively alleviate the inhibitory effects of sulfadiazine on photosynthesis and sustain ryegrass growth comparable to uncontaminated control. Structural equation model analysis demonstrated that biochar can control ARGs occurrence in soil effectively through both direct and indirect effects. Amplicon sequencing and untargeted metabolomics results indicated that biochar exhibited a limited restorative effect in mitigating high-dose sulfadiazine-induced disturbances to soil microbial community composition and functional profiles, relating to the significant decrease in microbial biomass and the diminished microbial carbon metabolism capability. All these findings provide a systematic evaluation of the efficacy and potential limitations of biochar in remediating sulfonamide-contaminated soils, offering valuable understanding for agricultural soil management.PMID:40367798 | DOI:10.1016/j.jenvman.2025.125702

Poult Sci. 2025 Apr 29;104(7):105187. doi: 10.1016/j.psj.2025.105187. Online ahead of print.ABSTRACTThe present study aimed to explore the effects of dietary phloretin (PT) on growth performance, immune response, and intestinal function in broilers with necrotic enteritis (NE). A total of 288 1-day-old Arbor Acres chicks were assigned to 3 groups, with 8 replicates per group and 12 chicks per replicate. Over 6 weeks, birds were fed a basal diet or the same diet supplemented with 200 mg/kg phloretin. Birds in the challenged groups were inoculated with coccildia during d 7 to 9 and Clostridium perfringens(CP) during d 14 to 18. Results showed that CP and coccidia challenge reduced the average daily gain and average daily feed intake, increased the feed conversion ratio of broilers, induced inflammation and oxidative stress, and inhibited mRNA expression levels for genes associated with intestinal barrier and nutrient transporters (P < 0.05). PT addition to the feed improved growth performance at early phase improved intestinal morphology, and elevated antioxidant capacity via increasing the activity of total antioxidant capacity and superoxide dismutase in the ileum in broilers with necrotic enteritis (P < 0.01). Dietary PT regulated the intesetinal immune function as observed by the increases in the content of secretory IgA in the ileum and decreased cytokines (Interleukin-1β, Interleukin-10) (P < 0.05). Moreover, NE infection significantly disrupted the balance of intestinal flora, and led to a lower level of short-chain fatty acids such as butyric acid concentration in the ileum, while PT improved the microbiota structure, and increased the intestinal acetic acid and butyric acid concentration (P < 0.001). Furthermore, metabolomics analysis indicated PT treatment improve plant secondary metabolites contents like phloretin 2'-o-glucuronide. Additionally, we observed a significant positive correlation among PT, Ligilactobacillus and butyric acid, and a positive correlation between Ligilactobacillus and plant secondary metabolites. Overall, PT supplementation could improve growth performance and ameliorate intestinal injury in broilers with necrotic enteritis by enhancing the antioxidant capacity and immune function, regulating intestinal flora structure and producing plant secondary metabolites.PMID:40367711 | DOI:10.1016/j.psj.2025.105187

Int Immunopharmacol. 2025 May 13;158:114829. doi: 10.1016/j.intimp.2025.114829. Online ahead of print.ABSTRACTBACKGROUND: CRLM (Colorectal liver metastasis), a prevalent form of distant metastasis in colorectal cancer, is a leading cause of mortality in affected patients. Despite advancements in immunotherapy for colorectal cancer, clinical benefits in CRLM patients remain limited. The immunosuppressive liver microenvironment plays a pivotal role in facilitating metastatic colonization and disease progression.METHODS: We performed fecal metabolomics in ABX (antibiotic-treated) mice and single-cell RNA sequencing on hepatic tissues from four cohorts: CRC (colorectal cancer) , CRLM, LCA-fed CRC, and LCA-fed CRLM mice, to delineate intergroup immune heterogeneity. Cellular and molecular profiling across groups was conducted via Luminex multiplex assays, flow cytometry, and immunofluorescence. Integrated multi-omics analyses elucidated LCA-driven pathways modulating metastatic progression RESULTS: We demonstrated that LCA (lithocholic acid), a gut microbiota-derived metabolite, activates TGR5 in hepatic CAFs (cancer-associated fibroblasts) to upregulate CCL3 secretion. Elevated CCL3 levels subsequently recruit MDSCs (myeloid-derived suppressor cells) into metastatic niches. While MDSCs primarily suppress T-cell activation, we identified a paradoxical role of MDSC-derived CCL2 in attenuating immunosuppression via CCR2 signaling, suggesting a compensatory pro-inflammatory axis within the tumor microenvironment CONCLUSIONS: These findings suggest new immunotherapeutic strategies for the treatment of CRLM.PMID:40367692 | DOI:10.1016/j.intimp.2025.114829

PLoS One. 2025 May 14;20(5):e0322480. doi: 10.1371/journal.pone.0322480. eCollection 2025.ABSTRACTPlants native to colder climates, higher elevations, or semi-arid regions have more phenolic compounds in their organs. Faced with the current climate crisis, the effects of global heating with overgrazing pressure on natural pastures are not fully recognized in the Himalaya-Karakoram and Hindukush (HKH) region. The objective of this research was to investigate how biological active compound accumulation and concentration of high-elevation plants change under the influence of simulated climate warming which was induced by open-top chambers. The bioactive profiling plant species from experimental units were investigated through High-Performance Liquid Chromatography (HPLC), and compared with control. That revealed a significant increase in the major phenolic acid and flavonoid compounds (Rutin, Quercetin, Myricetin, Gallic Acid, and Kaempferol). The accumulation of other minor compounds, such as Vanillic Acid, Syringic Acid, Ferulic Acid, and Catechin, showed species-specific variation in concentration. The species-specific responses indicated the dominant and positive adaptation species such as P. macrophylla, A. rupestris, A. penduncularis, P. hololeuca, P. alpina, and under stress could accumulate more secondary metabolites, explaining their capacity for adaptation. These species' proliferation under a stressed climate and higher elevation with grazing pressure provides insightful information about their exploitation of phenolic compounds which may alter the environmental sustainability.PMID:40367051 | DOI:10.1371/journal.pone.0322480

Ecotoxicol Environ Saf. 2025 May 13;298:118330. doi: 10.1016/j.ecoenv.2025.118330. Online ahead of print.ABSTRACTDespite the widespread presence of polyethylene terephthalate microplastics (PET MPs) in the environment, their biotoxicity, target organs, and underlying toxicological mechanism remain poorly understood. In this study, irregularly shaped PET MPs resembling those commonly found in natural environment were selected. Mice were orally administered different amounts of PET MPs (0, 5, 50, and 500 μg/day) for 17 weeks, after which relevant pathological and biochemical indicators were assessed. The results confirmed, for the first time, that PET MPs can induce oxidative stress, lipid accumulation, and apoptosis in liver cells, resulting in structural damage and functional abnormalities in the liver. Additionally, metabolomic analysis was combined with intestinal microbiota profiling to elucidate the potential toxicological mechanism. The data revealed that chronic exposure to high doses of PET MPs substantially altered the diversity of the intestinal flora. In particular, the relative abundances of Parasutterella, Muribaculum, and Turicibacter increased, accompanied by elevated levels of lipid metabolites such as linoleic acid, taurocholic acid, and sphingosine. These changes disrupted metabolic processes and accelerated lipid deposition in the mouse liver, thereby inducing hepatotoxicity. Moreover, a validation experiment confirmed that depletion of the gut microbiota in mice alleviated PET MPs-induced hepatotoxicity. These findings provide new insights into the toxicity of PET MPs in humans and other mammals.PMID:40367616 | DOI:10.1016/j.ecoenv.2025.118330

Ecotoxicol Environ Saf. 2025 May 13;298:118292. doi: 10.1016/j.ecoenv.2025.118292. Online ahead of print.ABSTRACTWhile nanomaterial-mediated metabolic reprogramming emerges as a promising anticancer strategy, the precise mechanisms remain elusive due to limited metabolomics investigations. The objective of this study is to design an aluminum (Al) based metal organic frameworks (Al-MOF) and investigate its cytotoxic effects on bladder cancer cells (T24), and elucidate the specific molecular mechanisms. Comprehensive characterization (scanning electron microscopy, particle size and potential analysis, infrared spectroscopy, powder X-ray diffraction, and N2 desorption/desorption experiment) confirmed the successful preparation of Al-MOF. Subsequently, in vitro assays demonstrated the selective cytotoxicity of Al-MOF, showing an inhibitory effect on the proliferation of T24 compared to human immortalized urothelial cells. At the same time, when the concentration of Al-MOF exceeded 100 μg/mL, it exhibited significant migration inhibition on T24. Then, the effect of Al-MOF on T24 metabolites was investigated using ultra-high performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry. After 24 h of incubation, we identified 38 key differential metabolites from expression patterns and metabolic pathways, predominantly in fatty acid synthesis. Research has found that Al-MOF reduced fatty acid biosynthesis by inhibiting FASN expression, thereby inhibiting the progression of T24. This work provides evidence of MOF-mediated intervention in cancer cell metabolism, offering valuable insights for the design of novel multifunctional nanotherapies.PMID:40367611 | DOI:10.1016/j.ecoenv.2025.118292

J Pharm Biomed Anal. 2025 May 8;264:116954. doi: 10.1016/j.jpba.2025.116954. Online ahead of print.ABSTRACTGastrodiae Rhizoma (Tianma, GR), the dried tuber of Gastrodia elata Bl., is a valuable herb for medicinal and dietary applications. Current markets feature three key cultivars: G. elata f. glauca (WTM), G. elata f. elata (HTM), and their hybrid (WHTM), with significant price variations yet lacking defined chemical authentication markers. Here, we implemented a pseudotargeted LC-MS/MS metabolomics strategy employing 534 optimized MRM transitions. This strategy was coupled with multivariate analysis - unsupervised principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) - of 40 authenticated batches, to decipher cultivar-specific chemical fingerprints. The approach identified 88 statistically validated markers, with 14 pivotal discriminators-primarily 4-Hydroxybenzyl alcohol derivatives-exhibiting distinct cultivar distribution patterns. This chemical blueprint serves as a tool for authentication in quality control and supports regulatory standard establishment for GR products.PMID:40367578 | DOI:10.1016/j.jpba.2025.116954

Poult Sci. 2025 May 7;104(8):105275. doi: 10.1016/j.psj.2025.105275. Online ahead of print.ABSTRACTFledgling broiler ducks vary in body weight and growth rate. The aim of this study was to investigate the relationship between serum metabolites and the intestinal microbiota in Cherry Valley broiler ducks with different finishing weights and to reveal differences in their metabolic regulation and microbial composition. Serum and cecum content samples were collected from Cherry Valley broiler ducks of different finishing weights. Metabolites were identified and compared using untargeted metabolomics, 16S rRNA gene sequencing, multivariate statistics and bioinformatics. Six key findings emerged. First, serum biochemical parameters showed that AST and ALT levels were significantly lower in the high weight group (Group H) than in the low weight group (Group L), and serum immunoglobulin IgG levels were significantly higher in group H. Second, the chorionic height to crypt depth ratio of the duodenum was significantly higher in group H than in group L. Third, the gut microbial community diversity or abundance was lower in broiler ducks in group L. Fourth, LEfSe analysis showed that the biomarker for group L was Streptococcus, whereas for group H it was Faecalibacterium. Fifth, a total of 127 differential metabolites were identified (49 up-regulated and 78 down-regulated). Finally, Spearman's correlation analysis showed that Spearman's correlation analyses showed that the Lipid-related serum metabolites were higher in low-body recombinant broiler ducks, mainly Lathosterol, Cholesterol, Cynaratriol and Leukotriene B4. In addition to lipid-associated serum metabolites in high-body recombination, The water-soluble vitamin-like metabolite Pantothenate and the antibiotic-like metabolite Tylosin were high. The cecum microbiota is strongly associated with metabolites, especially Faecalibacterium, unclassified Tannerellaceae, Subdoligranulum, Alistipes, and [Ruminococcus] torques_group, with which it exhibits strong Correlation. Broiler ducks with higher body weights have a better intestinal villous structure, enhanced digestion and absorption, higher levels of immunoglobulin secretion and superior growth performance. Broiler ducks with different body weights differed in plasma metabolites and cecum flora. Spearman's correlation analyses showed that the Correlation between differential metabolites and differential gut microbial genera.PMID:40367572 | DOI:10.1016/j.psj.2025.105275

Poult Sci. 2025 Apr 29;104(8):105233. doi: 10.1016/j.psj.2025.105233. Online ahead of print.ABSTRACTThis study systematically investigated the genetic and metabolic mechanisms underlying pigmentation in goose webbed feet by integrating histological, transcriptomic, and metabolomic analyses. Histological examinations revealed significant differences in melanin deposition among webbed feet of varying colors. Dark black webbed feet exhibited the highest melanin content, light black webbed feet showed moderate levels, and colorless webbed feet lacked detectable melanin. Transcriptomic analysis identified substantial variations in the expression levels of key genes involved in melanin biosynthesis, including TYRP1, PMEL, DCT, TYR, OCA2, MC1R, RAB38, WNT16, CAMK2A, and MLANA, between pigmented and colorless webbed feet. Notably, the OCA2 gene exhibited significantly higher expression in dark black webbed feet compared to light black webbed feet, underscoring its pivotal role in regulating pigmentation intensity. Enrichment analysis emphasized the importance of pathways related to tyrosine metabolism, melanin production, and amino acid biosynthesis in determining pigmentation differences. Metabolomic profiling supported these findings, revealing that L-tyrosine and 5,6-dihydroxyindole-2-carboxylic acid are critical metabolites in the melanin biosynthesis pathway. Specifically, elevated levels of L-tyrosine were detected in colorless webbed feet, likely due to inhibited melanin synthesis, whereas 5,6-dihydroxyindole-2-carboxylic acid levels were highest in dark black webbed feet, reflecting active melanin production. Correlation analysis between transcriptomic and metabolomic data further validated the central role of tyrosine metabolism and melanin biosynthesis pathways in pigmentation. In conclusion, this study employed multi-omics approaches to elucidate the critical role of the OCA2-centered genetic-metabolic regulatory network in melanin deposition of goose webbed feet, providing important insights into the molecular mechanisms of avian pigmentation and valuable references for poultry breeding.PMID:40367570 | DOI:10.1016/j.psj.2025.105233

Poult Sci. 2025 May 2;104(8):105258. doi: 10.1016/j.psj.2025.105258. Online ahead of print.ABSTRACTThe significant depigmentation of brown eggshells occurs in the in the late-phase laying hens, which directly affects consumer acceptance. However, the biological mechanism of eggshell depigmentation based on uterine metabolism has not been elucidated. In this study, a total of 4 group were as follows: 1) 65-week-old laying hens with normal color; 2) 65-week-old laying hens with light color; 3) 80-week-old laying hens with normal color; 4) 80-week-old laying hens with light color. Variations in the pigment contents, uterine antioxidant capacity, uterine microbiota, and uterine metabolomics were examined in current study. Results showed that significantly decreased L* values and increased a* and b* values were observed in the depigmentation group (P < 0.05). The protoporphyrin IX content of the uterus with eggshell depigmentation was significantly decreased in 65-week-old laying hens (P < 0.05). Uterine MDA content was significantly increased in the depigmentation groups at 65 and 80 weeks of age, accompanied by reduced SOD and increased IgA levels (P > 0.05). The abundance of Proteobacteria and Campilobacterota was markedly reduced in the uterus with eggshell depigmentation, whereas Firmicutes was elevated at 65 weeks of age (P < 0.05). Further, Psychrobacte as biomarkers can accurately distinguish between normal color and depigmentation in eggshells (AUC = 0.91). A total of 51 differential metabolites were significantly enriched in the down-regulated sphingolipid metabolism, linoleic acid metabolism, citrate cycle, oxidative phosphorylation, PPAR signaling pathway, FoxO signaling pathway, and apoptosis at 65 weeks of age (P < 0.05). Meanwhile, there were 82 differential metabolites were significantly up-regulated at 80 weeks of age, which mainly enriched in up-regulated linoleic acid metabolism, purine metabolism, and pentose phosphate pathway (P < 0.05). These findings elucidate the specific metabolic mechanisms responsible for eggshell depigmentation in 65- and 80-week-old laying hens, contributing to the improvement of eggshell depigmentation by the precise nutritional modulation in the late-phase laying hens.PMID:40367565 | DOI:10.1016/j.psj.2025.105258

J Agric Food Chem. 2025 May 14. doi: 10.1021/acs.jafc.4c12136. Online ahead of print.ABSTRACTAlginate oligosaccharide (AOS) is a structurally distinct carbohydrate derived from marine algae. In this study, AOS was obtained through the enzymatic hydrolysis of alginate, and the anti-inflammatory efficacy of AOS was assessed in lipopolysaccharide (LPS)-induced inflammatory Balb/c mice. AOS effectively suppressed the overexpression of TNF-α, IL-6, and MDA while restoring the reduced SOD activity. Histopathological analysis revealed that AOS significantly reduced the level of LPS-induced tissue edema, inflammatory infiltration, and villous destruction. Additionally, AOS notably upregulated tight junction proteins Claudin-1, Occludin, and ZO-1 expression. Transcriptomic and Western blot analyses indicated that AOS primarily mediated the restriction of the TLR4/MAPK/NF-κB pathway in the jejunum. Moreover, AOS ameliorated gut microbiota dysbiosis, such as increasing in Bacteroidota, alongside decreasing in Firmicutes, Campylobacter, and Desulfovibrio, respectively. Metabolomics demonstrated that AOS improved the LPS-induced reduction of short-chain fatty acids in the gut. These results provide compelling evidence supporting the potential of AOS against acute intestinal inflammation.PMID:40367367 | DOI:10.1021/acs.jafc.4c12136

PLoS Pathog. 2025 May 14;21(5):e1013092. doi: 10.1371/journal.ppat.1013092. Online ahead of print.ABSTRACTEpstein-Barr virus (EBV) is associated with multiple types of cancers, many of which express the viral oncoprotein Latent Membrane Protein 1 (LMP1). LMP1 contributes to both epithelial and B-cell transformation. Although metabolism reprogramming is a cancer hallmark, much remains to be learned about how LMP1 alters lymphocyte oncometabolism. To gain insights into key B-cell metabolic pathways subverted by LMP1, we performed systematic metabolomic analyses on B cells with conditional LMP1 expression. This approach highlighted that LMP highly induces de novo purine biosynthesis, with xanthosine-5-P (XMP) as one of the most highly LMP1-upregulated metabolites. Consequently, IMPDH inhibition by mycophenolic acid (MPA) triggered death of LMP1-expressing EBV-transformed lymphoblastoid cell lines (LCL), a key model for EBV-driven immunoblastic lymphomas. Whereas MPA instead caused growth arrest of Burkitt lymphoma cells with the EBV latency I program, conditional LMP1 expression triggered their death, and this phenotype was rescuable by guanosine triphosphate (GTP) supplementation, implicating LMP1 as a key driver of B-cell GTP biosynthesis. Although both IMPDH isozymes are expressed in LCLs, only IMPDH2 was critical for LCL survival, whereas both contributed to proliferation of Burkitt cells with the EBV latency I program. Both LMP1 C-terminal cytoplasmic tail domains critical for primary human B-cell transformation were important for XMP production, and each contributed to LMP1-driven Burkitt cell sensitivity to MPA. Metabolomic analyses further highlighted roles of NF-kB, mitogen activated kinase and protein kinase C downstream of LMP1 in support of XMP abundance. Of these, only protein kinase C activity was important for supporting GTP levels in LMP1 expressing Burkitt cells. MPA also de-repressed EBV lytic antigens, including LMP1 itself in latency I Burkitt cells, highlighting crosstalk between the purine biosynthesis pathway and the EBV epigenome. These results suggest novel oncometabolism-based therapeutic approaches to LMP1-driven lymphomas.PMID:40367275 | DOI:10.1371/journal.ppat.1013092

Sci Adv. 2025 May 16;11(20):eadp7063. doi: 10.1126/sciadv.adp7063. Epub 2025 May 14.ABSTRACTParkinson's disease (PD) is the second most common neurodegenerative disease, with a rapidly increasing prevalence worldwide. Biomarkers monitoring state and progression are urgently needed, and metabolomics from easily accessible biofluids holds the potential to elucidate pathophysiological underpinnings in PD. Several studies suggested metabolomic differences between patients and controls, but findings are controversial, and independent replication is scarce. We thus applied state-of-the-art, large-scale metabolomics in patients with idiopathic and monogenic PD and controls from two independent samples, analyzed by a strict meta-analysis approach. Thereby, we (i) debunked that l-Dopa medication and not disease status causes the most substantial metabolomic differences and (ii) identified polyamine metabolism alterations, partly, but not entirely associated with l-Dopa treatment. Furthermore, we found explorative but robust evidence for alterations in endocannabinoid metabolites; detected lipid metabolism alterations, highlighting potential crosslinks with alpha-synuclein pathology; and provided evidence for a metabolomic signature for the role of oxidative damage in patients with PRKN- and PINK1-linked PD.PMID:40367158 | DOI:10.1126/sciadv.adp7063