PubMed

Food Chem. 2025 Mar 19;480:143954. doi: 10.1016/j.foodchem.2025.143954. Online ahead of print.ABSTRACTThe objectives of this research were to analyze the effects of varying nitrogen application rates on fruit quality and antioxidant properties of blue honeysuckle through widely targeted metabolomics analysis. High nitrogen application resulted in a reduction in fruit size and soluble solid content, along with significant decreases in the levels of total anthocyanins, phenolic compounds, flavonoids, and antioxidant indices. Under low nitrogen, key flavonoids in fruit namely Kaempferol-7-O-glucoside, Morin 3-alpha-L-lyxopyranoside, and Quercetin-3-O-xyloside (Reynoutrin) showed the high peak areas, with SOD, POD, and CAT activities at 1742.19, 45,525.65, and 1065.13 U/g, but decreased under high nitrogen. The molecular docking analysis revealed affinity values of -5.39, -2.72, -4.37, -3.98, -4.04, -4.18, -2.51, -2.31, and - 4.08 kcal/mol for SOD, POD, and CAT. These three flavonoids play a crucial role in the antioxidant defense system by targeting different enzymes, and their reduced concentrations under high nitrogen conditions may impair the fruit's antioxidant capacity.PMID:40121874 | DOI:10.1016/j.foodchem.2025.143954

Chemosphere. 2025 Mar 22;377:144334. doi: 10.1016/j.chemosphere.2025.144334. Online ahead of print.ABSTRACTThe prevalence of polycyclic aromatic hydrocarbons and their oxygenated and nitrogen containing analogs in freshwater ecosystems are of concern due to their reported toxicity to several aquatic species including Daphnia magna. This study explored the molecular-level responses of phenanthrene (PHEN), 9,10-phenanthrenequinone (PHQ), and phenanthridine (PN) as little is known about the impacts of these pollutants on the metabolic profile of D. magna. For this purpose, D. magna was exposed to three sub-lethal concentrations of these pollutants for 24 h. To assess molecular-level responses, 52 polar metabolites were extracted from individual adult daphnids, and analyzed using a mass spectrometry-based targeted metabolomics approach. Exposure to PN resulted in the most statistically significant changes to the metabolic profile of D. magna followed by PHQ, and then PHEN exposures. After PN exposure, the biochemical pathway analysis showed that all exposure concentrations shared 21 perturbed metabolic pathways. However, the number of disrupted metabolic pathways increased with increasing exposure concentrations for PHEN and PHQ. The results suggest that PN and PHQ exposures are more disruptive due to the presence of reactive functional groups when compared to PHEN exposure. For the tested concentration ranges, the findings indicate that exposure to PN resulted in non-monotonic disruptions across exposure concentrations. In contrast, exposure to PHEN and PHQ elicited perturbations that were concentration-dependent. Although the reported median effective concentration (EC50) for PN is higher than PHEN and PHQ, our data shows that metabolomics captures molecular-level changes that may not be detected by traditional toxicity metrics.PMID:40121761 | DOI:10.1016/j.chemosphere.2025.144334

BMC Womens Health. 2025 Mar 22;25(1):135. doi: 10.1186/s12905-025-03676-5.NO ABSTRACTPMID:40121498 | DOI:10.1186/s12905-025-03676-5

Vet Res. 2025 Mar 22;56(1):65. doi: 10.1186/s13567-025-01494-z.ABSTRACTMycoplasma synoviae (M. synoviae) is a major bacterial pathogen that causes serious economic losses in the global poultry industry. Systemic changes in specific pathogen free White Leghorn egg-laying hens after M. synoviae infection were investigated using intra-tracheally inoculated animals. Samples were collected 10 days post-infection (dpi) (204-day-old) and 52 dpi (246-day-old). Infection caused air sac lesion, footpad swelling and oviduct atrophy. The qPCR and in situ hybridization showed that bacteria colonized the trachea and oviduct, and that bacterial loads in the magnum and uterus were significantly higher than in the infundibulum and isthmus. Histopathological examination revealed increased tracheal mucosal thickening accompanied by inflammatory cell infiltration, and that tubular glands of the uterus were edematous or dissolved. Infection also induced decreased egg production and eggshell strength, and eggshell apex abnormalities appeared at 14 dpi. Plasma metabolomics of hens analyzed by liquid chromatography-tandem mass spectrometry showed 168 and 128 differentially-expressed metabolites (DEM) at 10 and 52 dpi, respectively. Pathway analysis revealed that DEM at 10 dpi were enriched in five distinctive pathways: regulation of the actin cytoskeleton, neuroactive ligand-receptor interaction, sphingolipid metabolism, gap junctions, and necroptosis. In contrast, DEM at 52 dpi were enriched in fifteen pathways involved in steroid hormone biosynthesis, ferroptosis, the calcium signaling pathway, apelin signaling pathway, progesterone-mediated oocyte maturation, and oocyte meiosis. Combined metabolic analysis demonstrated that changes in ethylsalicylate, nicotinamide, (3-Methoxy-4-hydroxyphenyl) ethylene glycol sulfate, sphingosine-1-phosphate (d18:1), carnitine C24:6, and 15(R)-prostaglandin E1 correlated the best with M. synoviae infection. This study provides new insights into understanding pathogen mechanisms and signposts novel treatments for M. synoviae infection in poultry.PMID:40121482 | DOI:10.1186/s13567-025-01494-z

J Transl Med. 2025 Mar 22;23(1):359. doi: 10.1186/s12967-025-06375-9.ABSTRACTBACKGROUND: Understanding the evolving patterns of cardiovascular disease (CVD) burden attributable to ambient particulate matter pollution (APMP) is essential. Furthermore, research on the underlying mechanisms has mostly been limited to laboratory and animal models, with few large-scale population-based studies.METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, we analyzed disability-adjusted life years and mortality for CVD attributable to APMP (measured as particulate matter [PM]2.5) from 1990 to 2021. We examined shifts in burden between APMP and household air pollution (HAP), regional disparities by socio-demographic index (SDI), and predicted trends using a Bayesian age-period-cohort model. Additionally, we used UK Biobank (UKB) data (metabolomics: 230,000 + participants; proteomics: 50,000 +) to identify biomarkers mediating the association between PM2.5 exposure and CVD outcomes, and further analyzed their biological roles. Metabolic and proteomic signatures were constructed using regression and elastic net models, with predictive performance assessed via time-dependent receiver operating characteristic analysis. Life expectancy was evaluated using flexible parametric survival models. Subgroup analysis was conducted by age, sex, lifestyle, socioeconomic status, and genetic susceptibility.RESULTS: In 2021, the global CVD absolute burden attributable to APMP was more than double that of 1990, with significant regional disparities. The burden shifted from HAP to APMP, with 15% of CVD cases globally attributed to APMP. The CVD burden attributable to APMP increased with age and is projected to rise through 2030. In the UKB, approximately 30 metabolites, including albumin, mediated the association between PM2.5 exposure and CVD outcomes, primarily involving lipid and fatty acids metabolism. Over 60 proteins, including growth differentiation factor-15 and trefoil factor 2, mediated the association with CVD outcomes, enriched in cytokine-receptor interaction and leukocyte migration pathways. Metabolic and proteomic signatures outperformed PM2.5 alone in predicting 1-, 5-, and 10-year CVD outcomes. Participants in the lowest decile of PM2.5 exposure, metabolic, and proteomic signatures had longer life expectancy than those in the highest decile.CONCLUSION: The CVD burden attributable to APMP remains a critical public health concern. This study presents a novel approach for identifying and managing susceptible populations through metabolomic and proteomic perspectives.PMID:40121471 | DOI:10.1186/s12967-025-06375-9

Commun Biol. 2025 Mar 22;8(1):478. doi: 10.1038/s42003-025-07848-9.ABSTRACTGPR35 is an orphan G-protein coupled receptor that has been implicated in the development of cancer. GPR35 regulates the Na+/K+-ATPase's pump and signalling function. Here we show GPR35's critical role in ion flux that in turn controls cellular osmotic pressure and Na+-dependent transport in HepG2 and SW480 cells. GPR35 deficiency results in increased levels of intracellular Na+, osmotic stress and changes in osmolytes leading to increased cells size and decreased glutamine import in vitro and in vivo. The GPR35-T108M risk variant, which increases risk for primary sclerosing cholangitis and inflammatory bowel disease, leads to lower intracellular Na+ levels, and enhanced glutamine uptake. High salt diet (HSD) in wildtype mice resembles the intestinal epithelial phenotype of their Gpr35-/- littermates with decreased Goblet cell size and numbers. This indicates that GPR35's regulation of the Na+/K+-ATPase controls ion homeostasis, osmosis and Na+-dependent transporters.PMID:40121360 | DOI:10.1038/s42003-025-07848-9

Sci Rep. 2025 Mar 22;15(1):9945. doi: 10.1038/s41598-025-90467-5.ABSTRACTHashimoto's thyroiditis (HT) is a prevalent autoimmune disorder, yet the metabolic abnormalities associated with HT and their relationship to antibody positivity remain poorly understood. This study aimed to characterize the distinct metabolic profiles associated with thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in female patients with HT. Serum metabolomic analysis was performed on 14 TPOAb-positive patients, 4 TgAb-positive patients, and 14 sex-matched healthy controls, evaluating a total of 225 metabolites. Partial least squares discriminant analysis (PLS-DA) revealed significant metabolic differences among the groups, identifying 36 key metabolites. Of these, 13 metabolites showed significant differences between the TPOAb-positive group and healthy controls, while 23 metabolites exhibited marked differences between the TgAb-positive group and controls. Further correlation analysis revealed a moderate positive association between TgAb and phenylacetyl-L-glutamine, while TPOAb was strongly correlated with LPC 16:0 sn-1. Additionally, metabolic pathway analysis showed significant activation of glycine, serine, and threonine metabolism in the TPOAb-positive group, whereas the TgAb-positive group exhibited enhanced activity in galactose metabolism. These findings suggest that TPOAb and TgAb positivity are associated with distinct metabolic profiles, reflecting their differential roles in metabolic pathways linked to Hashimoto's thyroiditis. This study provides valuable exploratory evidence of metabolic abnormalities in HT under different antibody-positive states, laying the foundation for future large-scale investigations to elucidate the underlying mechanisms.PMID:40121266 | DOI:10.1038/s41598-025-90467-5

J Hazard Mater. 2025 Mar 21:137926. doi: 10.1016/j.jhazmat.2025.137926. Online ahead of print.NO ABSTRACTPMID:40121115 | DOI:10.1016/j.jhazmat.2025.137926

Plant J. 2025 Mar;121(6):e70092. doi: 10.1111/tpj.70092.ABSTRACTAvicennia marina is a dominant mangrove plant that inhabits coastal intertidal wetlands where are featured by low oxygen and nitrogen (N), but high sulfur (S). Its pneumatophore is a unique characteristic of its root system. To understand the roles of the pneumatophore in carbon (C), N, and S metabolisms for intertidal adaptation, we firstly compared the anatomy between aboveground pneumatophore (PA), belowground pneumatophore (PB) and feeding root. The photosynthetic oxygen evolution from PA was assayed by non-invasive micro-test technology, and the metabolisms of C, N, and S between PA and PB were comparatively analyzed by transcriptome and metabolome approaches. The results illustrated that most genes related to photosynthetic C assimilation and S reduction were significantly up-regulated in PA, while genes associated with N uptake, transport, and reduction were significantly up-regulated in PB. Additionally, the expression level of the gene for sulfite oxidase was up-regulated in PA, indicating a tight regulation of S assimilation by PA. Importantly, our findings revealed that key reductases for both S and N assimilation are ferredoxin-dependent, with electrons supplied by the corticular photosynthesis in PA. Integrative multi-omics analysis showed that methylthioadenosine (MTA) was negatively associated with genes related to serine and cysteine biosynthesis but positively connected with genes related to the Yang cycle. This suggests a pivotal role of MTA in coordinating C, N, S, and ethylene metabolism in pneumatophores. The overall results illustrate that the green cortex of PA functions analogously to a leaf, providing reductants and C skeletons for N and S metabolism while coordinating with ethylene metabolism. This facilitates the adaptation of A. marina pneumatophore to the intertidal habitat.PMID:40121018 | DOI:10.1111/tpj.70092

Bioresour Technol. 2025 Mar 20:132426. doi: 10.1016/j.biortech.2025.132426. Online ahead of print.ABSTRACTThe current study investigated the impact of biochar on root exudate chemistry and characterized exudate molecule abundance as a function of biochar application rates. In exudates trickled over biochar, organic oxygen-rich compounds were the most common molecules stemming from biochar, comprising 67 % of the abundance of biochar-derived compounds. Eighty percent of these compounds stemming from biochar were hydrophilic. On the other hand, biochar-retained molecules were mostly lipophilic (87 %) and consisted mainly of lipid-related compounds (52 %). In addition, root-exuded molecules with ≥ 20 aliphatic-carbon atoms were retained by biochar (representing 44 % of all retained molecules) but were not released from biochar. These findings indicate that biochar can increase the hydrophilic:lipophilic balance of root exudates. In soil, this change could influence the spatial heterogeneity of dissolved organic matter and the role of root exudates in modulating plant-plant and plant-microbe interactions.PMID:40120991 | DOI:10.1016/j.biortech.2025.132426

Fitoterapia. 2025 Mar 20:106486. doi: 10.1016/j.fitote.2025.106486. Online ahead of print.ABSTRACTThis study aimed to explore the mechanisms of Feiyanning formula (FYN) on acute lung injury (ALI) using pharmacokinetics combined with network pharmacology strategy. Firstly, pharmacokinetic studies of 13 major bioactive components in normal and ALI mice were conducted using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Secondly, metabolomics was utilized to explore the metabolites affected by FYN. Finally, the network pharmacology was used to analyze the pharmacological mechanism of FYN's pharmacokinetic target components in ALI treatment, with western blotting (WB) experiment performed for verification. The pharmacokinetic results showed that compared to normal mice, the Cmax and AUC0-t of wogonin, oroxylin A, liquiritigenin, tetrandrine, and fangchinoline were significantly increased in ALI mice. The results of the lung tissue distribution showed that compared to normal mice, the AUC0-t of wogonin and oroxyloside was significantly increased in ALI mice; the Cmax of wogonoside and norwogonin was significantly increased in ALI mice. Metabolomics analysis showed that FYN may alleviate LPS-induced lung inflammation in mice by regulating related pathways including purine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis in both serum and lung tissue. Network pharmacology identified 110 overlapping genes between the 13 absorbed components and ALI-related targets. In KEGG enrichment analysis, the PI3K/AKT signaling pathway was identified as a significant pathway. WB experiment confirmed that FYN reduced the expression ratios of p-PI3K/PI3K, p-AKT1/AKT1, p-EGFR/EGFR, and TLR4 levels in lung tissue of ALI mice. This study might offer a solid foundation for evaluating the clinical efficacy of FYN.PMID:40120984 | DOI:10.1016/j.fitote.2025.106486

Int J Biol Macromol. 2025 Mar 20:142363. doi: 10.1016/j.ijbiomac.2025.142363. Online ahead of print.ABSTRACTPectins, a complex class of polysaccharides, are prominently represented by HG-chains, which are both abundant and extensively studied. Bacteroides species exhibit a remarkable ability to metabolize plant- and animal-derived polysaccharides, including the degradation of HG-type pectins through polysaccharide utilization locus (PUL). However, the effects of structurally diverse HG-type pectins on PUL expression, metabolite production, and metabolic pathways of Bacteroides remain unclear. Addressing this, this study chose HG-type pectins with different molecular weights from citrus (CP) and pomelo (PP), identified Bacteroides species capable of utilizing these pectins, studied the resulting metabolites through non-targeted metabolomics coupled with short-chain fatty acids analysis, and examined the activation of PUL and metabolic pathways by transcriptomic studies. The results showed that Bacteroides thetaiotaomicron A4 and Bacteroides caccae K9 could utilize HG-type pectins with different molecular weights. The production of propionic acid by Bacteroides thetaiotaomicron A4 was significantly affected by the molecular weight of pectins. Utilizing CP, B. thetaiotaomicron A4 enriched metabolites such as carbohydrates, amino acids, peptides, amines, and significantly enhanced pathways such as sphingolipid metabolism and drug metabolism (other enzymes) through PUL75, PUL63, and PUL55. In contrast, when using PP, B. thetaiotaomicron A4 enriched similar metabolites and further upregulated pathways related to sphingolipid metabolism and pyrimidine metabolism. The molecular weight of HG-type pectins differentially affected the expression of carbohydrate-active enzymes and metabolic pathways, resulting in different metabolite profiles. This study aims to contribute to the understanding of structure-activity relationship between pectins and gut microbiota and to inform precision nutrition strategies.PMID:40120915 | DOI:10.1016/j.ijbiomac.2025.142363

Brain Behav Immun. 2025 Mar 20:S0889-1591(25)00110-2. doi: 10.1016/j.bbi.2025.03.025. Online ahead of print.ABSTRACTAutism spectrum disorder (ASD) is characterized by impaired social interaction and repetitive stereotyped behavior, and effective interventions for the core autistic symptoms are currently limited. This study examines the protective role of L-tyrosine in alleviating ASD-like behavioral disorders in a valproic acid (VPA)-induced ASD mouse model and explores the underlying mechanisms via integrated multi-omics. We first investigated the potential of dietary L-tyrosine in mitigating autistic behavior. Subsequently, 16S rRNA sequencing, hippocampal transcriptomics, and neurotransmitter metabolome were employed to elucidate the underlying mechanism. Further, we conducted transplantation of the L-tyrosine-regulated microbiota in VPA-induced ASD mice. The results showed that L-tyrosine supplementation significantly mitigates ASD-like behavioral disorders, alleviates social communication deficits, and reduces repetitive behavior in autistic mice. L-tyrosine also attenuates the neuronal loss caused by VPA treatment in the DG and CA1 hippocampal regions in mice. The hippocampi of the L-tyrosine-treated mouse model for ASD displays modified gene expression profiles and different neurotransmitter levels. L-tyrosine also mitigates colonic barrier damage and amends the gut microbial composition and function. The integrative transcriptomic, metabolomic, and microbiome analysis shows strong connections between the hippocampal genes, neurotransmitters, and gut microbiota affected by L-tyrosine. The transplantation of microbiota from L-tyrosine-treated mice to VPA-induced ASD mice recipients recapitulated the preventive and protective effects of L-tyrosine on autistic behavior disorders. These findings suggest that dietary L-tyrosine may represent a viable, effective treatment option for managing the physiological and behavioral deficits associated with ASD.PMID:40120833 | DOI:10.1016/j.bbi.2025.03.025

Environ Res. 2025 Mar 20:121452. doi: 10.1016/j.envres.2025.121452. Online ahead of print.ABSTRACTUranium/cadmium (U/Cd) pollution poses a significant global environmental challenge, and phytoremediation offers a sustainable solution for heavy metal contamination. However, the mechanisms by which plants survive U/Cd stress remain unclear. Here, we conducted soil culture experiments of moso bamboo seedlings under U/Cd stress (U, Cd and U + Cd) to examine the effects of it on plant growth, mineral metabolism, and rhizosphere micro-environment. Our findings reveal that U/Cd stress inhibits seedling growth, enhances reactive oxygen species damage, and bolsters the antioxidant system. Additionally, Partial Least Squares Path Modeling (PLS-PM) was employed to uncover potential tolerance mechanisms in moso bamboo under U/Cd stress. U/Cd is mainly distributed in the root cell walls and also exists predominantly in the residual state within the roots. Correspondingly, U and Cd significantly disrupt mineral metabolism in plant. Metabolomic analyses indicate that U/Cd markedly suppress amino acid metabolism pathways, while they stimulate carbon metabolism to mitigate toxicity. Furthermore, U/Cd stress disrupts the rhizosphere microbial community structure, and the competitive interaction of nitrogen functions exists between rhizosphere microorganism and bamboo roots. PLS-PM reveal the U/Cd stress impacts the interaction of the soil-rhizosphere-plant system. Together, these findings offer new insights into the response mechanism of bamboo plants to heavy metal stress, and provide a theoretical foundation for screening heavy metal tolerant plants and managing mining areas.PMID:40120735 | DOI:10.1016/j.envres.2025.121452

J Ethnopharmacol. 2025 Mar 20:119647. doi: 10.1016/j.jep.2025.119647. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The deciphering of effective components is crucial for understanding the role they play and how they function in traditional Chinese medicine (TCM) formulae. However, this remains a significant challenge for these complex systems with multiple components, targets, and pathways, despite their therapeutic benefits.AIM OF THE STUDY: Three-dimensional pattern recognition of exogenous components correlated with endogenous metabolites was proposed to discover the effective components of Gualou-Xiebai-Banxia decoction (GXB), a famous classical TCM formula for effective improvement of atherosclerosis (AS).MATERIALS AND METHODS: The potential effective exogenous components were determined by three-dimensional pattern recognition of abundance, bioavailability and AS-related activity. The efficacy of GXB in attenuating AS was evaluated using an Apolipoprotein E-deficient (ApoE-/-) mice model subjected to a high-fat diet regimen. Plasma metabolomics was developed to dig out GXB efficacy-related endogenous metabolites. Next, the potential effective exogenous components and GXB efficacy-related endogenous metabolites were combined with AS targets to develop correlation analysis, so as to explore candidate effective components and potential mechanisms of GXB. Further, the effective components were validated by oxidized low-density lipoprotein-induced RAW 264.7 macrophages.RESULTS: A total of 30 potential effective exogenous components in GXB were ascertained by three-dimensional pattern recognition after conducting Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) analysis. GXB demonstrated a significant ameliorative effect on atherosclerotic symptoms in ApoE-/- mice under a high-fat diet, as evidenced by decreasing serum lipid levels, atherosclerotic plaques (aorta and aortic root) and IL-6 content. Subsequently, metabolomics results revealed that it was associated with the regulation of endogenous metabolites, including organic acids, amino acid, fatty acids and glycerophospholipid. Next, the correlation analysis was constructed with AS targets by the network of "potential effective exogenous components-AS targets-endogenous metabolites", tentatively inferring that 18 exogenous components were candidate effective components, and lipid metabolism was the major regulation pathway of GXB. Furthermore, GXB suppressed lipid accumulation in vivo/vitro through increasing expressions of PPAGγ, ABCA1, ABCG1, and SR-B1 related to cholesterol efflux. Cucurbitacin B and 5(6)-ene-macrostemonoside B were demonstrated as the effective components with inhibitory activity on foam cell formation and lipid accumulation.CONCLUSION: Three-dimensional pattern recognition of exogenous components correlated with endogenous metabolites was proposed and effectively utilized to demystify the effective components of GXB in AS prevention. This strategy also provided a reference for the related studies of other classical TCM formulae.PMID:40120703 | DOI:10.1016/j.jep.2025.119647

Genomics. 2025 Mar 20:111035. doi: 10.1016/j.ygeno.2025.111035. Online ahead of print.ABSTRACTThe long-term selection for meat has led to the poor egg production efficiency in broiler. In this study, we analyzed the transcriptional levels of hypothalamus and ovary during the pre-laying (PP) and laying periods (LP) of broiler breeders. By combining these with the levels of reproductive hormones and ovarian metabolism, to reveal the neuroendocrine control mechanism of ovarian development. Results showed that during LP, the number of LYFs, SYFs and WFs, the thickness of the granular cell layer, and the serum LH, FSH, P4 and E2 levels were significantly increased (P < 0.05). A total of 1188 and 2481 differentially expressed genes (DEGs) were detected in hypothalamus and ovary, respectively. 1972 significantly differentially metabolites (DMs) were detected in ovary. In hypothalamus, the expression of neuroendocrine regulatory genes such as TRH, AVT, VIP, and NYB in the Neuroactive ligand-receptor interaction pathway regulated the LH and FSH secretion via the HPG axis. In ovary, the promotion of GCs proliferation may occur through the glycerophospholipid metabolism pathway, which increased the thickness of the GCs layer. This helped to receive gonadotropin signals and increased P4 and E2 secretion. Meanwhile, the decreased expression levels of ovarian development inhibitory factors in the TGF-beta signaling pathway, including BMP2, BMP4, BMP15 and AMHR2, and the increased expression levels of MMPs, including MMP9, MMP11 and MMP13, may regulate the synthesis of metabolites associated with steroid hormone secretion and ovarian development, such as E2, E2-3S, 7α-OH-DHEA, CHO and AD. These genes and metabolites may play an important role in HPG axis in regulating ovarian development.PMID:40120699 | DOI:10.1016/j.ygeno.2025.111035

Am J Transplant. 2025 Mar 20:S1600-6135(25)00147-9. doi: 10.1016/j.ajt.2025.03.018. Online ahead of print.ABSTRACTOptimized static cold storage has the potential to improve preservation of organs most vulnerable to ischemia reperfusion injury. Data from lung transplantation suggest that storage at 10°C improves mitochondrial preservation and subsequent allograft function compared to conventional storage on ice. Using a porcine model of donation after circulatory death (DCD), we compared static storage of livers at 10°C to ice. Livers (N=5 per group) underwent ten hours of storage followed by four hours of normothermic machine perfusion (NMP) for real-time allograft assessment. Allografts were compared using established NMP viability criteria, tissue immunostaining, and tissue metabolomics. 10°C stored livers demonstrated lower portal venous vascular resistance and greater hepatic artery vasoresponsiveness. Lactate clearance during NMP was similar between groups. 10°C stored livers showed favorable biochemical parameters of biliary viability, including greater bile volume, pH, and bicarbonate. Metabolomics analysis revealed increased aerobic respiration, improved electron transport chain function, and less DNA damage after reperfusion of livers stored at 10°C. Static storage of DCD livers with extended cold ischemic time at 10°C demonstrates superior allograft function with evidence of improved biliary viability and mitochondrial function compared to ice. These data suggest that storage at 10°C should be considered for translation to clinical practice.PMID:40120647 | DOI:10.1016/j.ajt.2025.03.018

Cell Stem Cell. 2025 Mar 20:S1934-5909(25)00088-8. doi: 10.1016/j.stem.2025.02.017. Online ahead of print.ABSTRACTNon-energetic roles for glucose are largely unclear, as is the interplay between transcription factors (TFs) and ubiquitous biomolecules. Metabolomic analyses uncovered elevation of intracellular glucose during differentiation of diverse cell types. Human and mouse tissue engineered with glucose sensors detected a glucose gradient that peaked in the outermost differentiated layers of the epidermis. Free glucose accumulation was essential for epidermal differentiation and required the SGLT1 glucose transporter. Glucose affinity chromatography uncovered glucose binding to diverse regulatory proteins, including the IRF6 TF. Direct glucose binding enabled IRF6 dimerization, DNA binding, genomic localization, and induction of IRF6 target genes, including essential pro-differentiation TFs GRHL1, GRHL3, HOPX, and PRDM1. These data identify a role for glucose as a gradient morphogen that modulates protein multimerization in cellular differentiation.PMID:40120584 | DOI:10.1016/j.stem.2025.02.017

Chemosphere. 2025 Mar 21;377:144263. doi: 10.1016/j.chemosphere.2025.144263. Online ahead of print.ABSTRACTErythromycin (ERY) is a commonly used antibiotic found in wastewater effluents and the environment globally. Due to the bioactivity by which they kill and prevent bacterial growth, ERY and other antibiotics may have significant unwanted impacts on the gut microbiome of fishes. The overall objective of this project was to assess effects on the gut microbiome in response to exposure to ERY alone or in a mixture with other common antibiotics, which was accomplished in two experiments. The objectives of experiment 1 as a pilot study were to understand uptake and depuration of ERY in juvenile rainbow trout (RBT) over a 7-d exposure to three concentrations of ERY followed by a 7-d depuration period. Furthermore, throughout the study changes in gut microbiome were assessed. In experiment 2, an identical experimental design was used to assess the effects of a mixture of antibiotics containing, in addition to ERY, 100 μg/g each of ampicillin, metronidazole, and ciprofloxacin. In that study, three matrices were analyzed, with gut collected for 16S rRNA metabarcoding, blood plasma for non-targeted metabolomics, and brain tissue for mRNA-seq analysis. ERY was relatively quickly depurated from fish and gut microbiome dysbiosis was observed at 7 d after exposure, with a slight recovery after the 7-d depuration period. A greater number of plasma metabolites was dysregulated at 14 d compared to 7 d revealing distinct temporal dynamics compared to gut microbiome dysbiosis. Furthermore, several transformation products of antibiotics and biomarker metabolites were observed in plasma due to antibiotic exposure. The transcriptome of the brain was only slightly altered due to antibiotic exposure. Results of these studies will help inform aquaculture practitioners and risk assessors when assessing the potential impacts of antibiotics present in fish feed and the environment, with implications for host health.PMID:40120561 | DOI:10.1016/j.chemosphere.2025.144263

Phytomedicine. 2025 Mar 15;141:156655. doi: 10.1016/j.phymed.2025.156655. Online ahead of print.ABSTRACTBACKGROUND: Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.PURPOSE: This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.METHODS: The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.RESULTS: RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.CONCLUSION: This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.PMID:40120542 | DOI:10.1016/j.phymed.2025.156655