PubMed

Gut Microbes. 2025 Dec;17(1):2467235. doi: 10.1080/19490976.2025.2467235. Epub 2025 Feb 16.ABSTRACTThe gut microbiota-derived metabolite indole-3-propionic acid (IPA) plays an important role in maintaining intestinal mucosal homeostasis, while the molecular mechanisms underlying IPA regulation on mucosal CD4+ T cell functions in inflammatory bowel disease (IBD) remain elusive. Here we investigated the roles of IPA in modulating mucosal CD4+ T cells and its therapeutic potential in treatment of human IBD. Leveraging metabolomics and microbial community analyses, we observed that the levels of IPA-producing microbiota (e.g. Peptostreptococcus, Clostridium, and Fournierella) and IPA were decreased, while the IPA-consuming microbiota (e.g. Parabacteroides, Erysipelatoclostridium, and Lachnoclostridium) were increased in the feces of IBD patients than those in healthy donors. Dextran sulfate sodium (DSS)-induced acute colitis and CD45RBhighCD4+ T cell transfer-induced chronic colitis models were then established in mice and treated orally with IPA to study its role in intestinal mucosal inflammation in vivo. We found that oral administration of IPA attenuated mucosal inflammation in both acute and chronic colitis models in mice, as characterized by increased body weight, and reduced levels of pro-inflammatory cytokines (e.g. TNF-α, IFN-γ, and IL-17A) and histological scores in the colon. We further utilized RNA sequencing, molecular docking simulations, and surface plasmon resonance analyses and identified that IPA exerts its biological effects by interacting with heat shock protein 70 (HSP70), leading to inducing Th1/Th17 cell apoptosis. Consistently, ectopic expression of HSP70 in CD4+ T cells conferred resistance to IPA-induced Th1/Th17 cell apoptosis. Therefore, these findings identify a previously unrecognized pathway by which IPA modulates intestinal inflammation and provide a promising avenue for the treatment of IBD.PMID:39956891 | DOI:10.1080/19490976.2025.2467235

Commun Biol. 2025 Feb 16;8(1):248. doi: 10.1038/s42003-025-07728-2.ABSTRACTMedium-chain alkanes have strong ecological impacts on marine ecosystems due to their persistence, toxicity, and ability to travel long distances. Microbial degradation is the dominant and ultimate removal process for n-alkanes in the deep ocean, where high hydrostatic pressure (HHP) regulates microbial activity. To gain insight into the impact of hydrostatic pressure (HP) on n-alkane degradation, we applied the deep-ocean experimental simulation to culture Alcanivorax xenomutans A28, a novel piezotolerant bacterium strain from trench sediment, with n-C16 as the sole carbon source under different HPs (0.1, 40, and 80 MPa). Activity analysis demonstrated that HHP stimulated the n-C16 complete mineralization ratio. Transcriptomic and metabolomic analyses showed that HHP induced the intracellular oxidative stress and accelerated the tricarboxylic acid (TCA) cycle. These results indicate a shift of n-alkanes biodegradation pattern regulated by HP, elucidating the fate and ecological risk of n-alkanes in the deep ocean.PMID:39956881 | DOI:10.1038/s42003-025-07728-2

Physiol Plant. 2025 Jan-Feb;177(1):e70119. doi: 10.1111/ppl.70119.ABSTRACTThe cell cycle is predominantly controlled by Cyclins/Cyclin-Dependent Kinases (Cyc/CDK) complexes, which phosphorylate targets involved in cellular proliferation. Evidence suggests that Cyc/CDK targets extend beyond traditional proteins and include enzymes that regulate the central carbon metabolism. Maize embryo axes rapidly internalize and metabolize glucose. After 24 h of imbibition in glucose-rich media, axes exhibited increased length and weight, with more pronounced effects at 72 h. This morphology enhancement was impaired when RO-3306, a specific CDK inhibitor, was added. The protein profile of maize embryo extracts at 18 and 24 h indicated altered phosphorylation patterns following CDK activity inhibition. Metabolomic analysis at 24 h of imbibition revealed that maize embryos without sugar in the media, with or without RO-3306, had a decreased sugar and amino acid content. Conversely, axes exposed to glucose demonstrated increased conversion into various mono and di-saccharides such as fructose, mannitol, galactose, and maltose but not sucrose. This pattern was reversed upon the addition of RO-3306. Glucose promoted the accumulation of amino acids such as cysteine, valine, leucine, and intermediates of the tricarboxylic acid (TCA) cycle, such as malate and citrate. The CDK inhibitor redirected the glucose metabolism toward increased serine levels, followed by other amino acids like phenylalanine, valine, and leucine. Additionally, TCA cycle intermediates and sterols significantly decreased. Overall, these results contribute to understanding the role of CDK in maize morphogenesis during germination and underscore its impact on modulating various central carbon pathways, including glycolysis, amino acid catabolism/anabolism, TCA cycle, and sterols biosynthesis.PMID:39956791 | DOI:10.1111/ppl.70119

Physiol Plant. 2025 Jan-Feb;177(1):e70117. doi: 10.1111/ppl.70117.ABSTRACTSoil alkalization is a global ecological problem that constrains food security and sustainable socio-economic development. As a wild relative of soybean, wild soybean (Glycine soja) exhibits strong salt and alkali stress resistance and its cotyledons play a key role during the emergence (VE) stage. This study aimed to compare variations in growth parameters, cotyledon ultrastructure, photosynthetic physiology, mineral ion and metabolite contents, and gene expression in two ecotypes of wild soybean to elucidate the regulatory mechanisms underlying alkali stress resistance in salt-tolerant wild soybean cotyledons during the VE stage. The results showed that salt-tolerant wild soybean cotyledons exhibited relatively stable growth parameters, dense and orderly chloroplast structure, high photosynthetic rates, as well as high K+ and Ca2+ contents under alkali stress. Metabolomics, transcriptomics, and weighted gene co-expression network analyses revealed that salt-tolerant wild soybean cotyledons adapted to alkali stress during the VE stage by enhancing photosynthetic carbon assimilation pathways, increasing methionine and proline biosynthesis, and enhancing gamma-aminobutyric acid biosynthesis, thereby maintaining a stable carbon and nitrogen balance. In addition, upregulation of the expression of ICL, MS, and ACO2 led to the accumulation of various organic acids, such as pyruvic, aconitic, succinic, oxalic, malic, and fumaric acids, thereby promoting the synthesis of organic acid metabolism modules. This study provides novel insights into the key metabolic modules by which wild soybeans resist alkali stress.PMID:39956781 | DOI:10.1111/ppl.70117

Trends Mol Med. 2025 Feb 15:S1471-4914(25)00016-4. doi: 10.1016/j.molmed.2025.01.016. Online ahead of print.ABSTRACTMetabolomics has emerged as a transformative tool in precision oncology, with substantial potential for advancing biomarker discovery, monitoring treatment responses, and aiding drug development. Integrating artificial intelligence (AI) into metabolomics optimizes data acquisition and analysis, facilitating the interpretation of complex metabolic networks and enabling more effective multiomics integration. In this opinion, we explore recent advances in the application of metabolomics within precision oncology, emphasizing the unique advantages that AI-driven metabolomics offers. We propose that AI not only complements but also amplifies the potential of current platforms, accelerating research progress and ultimately improving patient outcomes. Finally, we discuss the opportunities and challenges involved in translating AI-driven metabolomics into clinical practice for precision oncology.PMID:39956738 | DOI:10.1016/j.molmed.2025.01.016

J Cyst Fibros. 2025 Feb 15:S1569-1993(25)00055-4. doi: 10.1016/j.jcf.2025.02.003. Online ahead of print.ABSTRACTBACKGROUND: In individuals with cystic fibrosis (CF), respiratory viral infections frequently result in hospitalization and have been linked to secondary bacterial infection and colonization, highlighting viral infections as possible contributors to CF lung disease progression. We hypothesized that expression of antiviral host defense genes is dysregulated in CF airway epithelia.METHODS: We infected primary CF and Non-CF airway epithelia with respiratory syncytial virus (RSV) and characterized their responses at 12 hr, 24 hr, 48 hr, 72 hr, and 120 hr post infection (hpi) by RNA sequencing (RNAseq).RESULTS: Our analysis revealed strikingly different gene expression profiles for the CF and Non-CF epithelia over the course of the infection. While both CF and Non-CF cells exhibited an early signature for interferon signaling and antiviral defense pathways, this response was relatively exaggerated and sustained in CF epithelia. We also observed, in both genotypes, a transient downregulation of cilia-associated genes and loss of ciliary activity by 72 hpi. Interestingly, recovery of cilia activity was delayed in the CF epithelia.CONCLUSIONS: These findings further our understanding of innate immune dysfunction in the CF airway epithelium and suggest that virus-induced cilia injury may further compromise host defenses in CF airways.PMID:39956716 | DOI:10.1016/j.jcf.2025.02.003

J Nutr. 2025 Feb 14:S0022-3166(25)00091-4. doi: 10.1016/j.tjnut.2025.02.011. Online ahead of print.ABSTRACTBACKGROUND: Prenatal alcohol exposure (PAE) impairs fetal growth and brain development. Dysregulated placental function contributes to these deficits. Whether PAE also disrupts its metabolic functions to impede fetal development is unclear.OBJECTIVES: We performed untargeted metabolomics to gain mechanistic insights on how PAE impacts placental metabolism and fetal nutrient availability.METHODS: Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or isocaloric maltodextrin (CON) daily on embryonic days (E) E8.5 through E17.5. We performed untargeted metabolomics on placentas harvested at E17.5.RESULTS: Alcohol reduced placental glucose and glycolytic intermediates and increased TCA cycle intermediates, suggesting a shift from glucose to lipids to meet its high energetic demands. This was complemented by elevations in intermediates of the pentose phosphate and glucosamine pathways, indicating a diversion of glucose into non-oxidative fates. Alcohol also decreased aspartate and asparagine, consistent with the limited glucose availability and increased fetal demand for nitrogen acceptors to support its increased gluconeogenesis and urea production. Alcohol also caused a selective increase in purine metabolites despite the limited availability of donor sources glucose, serine, glycine, glutamine, and asparagine. Uridine nucleotides were also elevated and may represent an adaptive change to meet the increased need for thiamin pyrophosphate in the oxidative decarboxylations of the TCA cycle and pentose phosphate pathways. Decreases in multiple oxylipins having anti-vasoconstriction actions could be a mechanism by which alcohol alters the placental vasculature and promotes vasoconstriction. Importantly, the selective and strong correlation of these dysregulated metabolites with reduced fetal brain weight, but not body weight, affirms the importance of the placenta-brain axis and placental metabolism on brain development.CONCLUSIONS: Alcohol causes metabolic dysregulation and reprogramming of the late-term placenta. These changes limit fetal nutrient availability and contribute to the reduced brain development and cognitive impairments that partly typify PAE.PMID:39956392 | DOI:10.1016/j.tjnut.2025.02.011

Metabolism. 2025 Feb 14:156161. doi: 10.1016/j.metabol.2025.156161. Online ahead of print.ABSTRACTThe brain is rich in lipids, and disorders or abnormalities in lipid metabolism can induce neurotoxicity. Ceramides are the central intermediates of sphingolipid metabolism. This study was designed to investigate the potential lipotoxicity of ceramides in brain ischemia. First, a pseudo-targeted lipidomics analysis of plasma samples from stroke patients found significantly elevated levels of long-chain ceramides. A similar observation was made in mice subjected to permanent middle cerebral artery occlusion (pMCAO) surgery. In cultured cells, it was found that the altered ceramides were mainly derived from astrocytes via de novo pathway, and SPTLC2 was a key regulator because Sptlc2 knockdown largely blocked ceramide production. Ceramides induced astrocyte activation and triggered oxidative stress to impair mitochondrial homeostasis by increasing mitochondrial permeabilization. Moreover, ceramides triggered the formation of voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane, through which mtDNA was released into the cytoplasm. Similar to oxygen and glucose depletion treatment, ceramides also increased cGAS activity and STING protein expression. However, this activity was diminished in the presence of the mitochondrial ROS scavenger SKQ1, indicating the involvement of oxidative stress in ceramide action. By facilitating cGAS/STING signaling cascades, ceramides resultantly induced interferon response to aggravate inflammatory damage in the ischemic brain. To address the impact of ceramides on brain ischemic injury in vivo, ceramide generation was blocked in the brain by injection of AAV9-Sptlc2 shRNA in pMCAO mice. Sptlc2 knockdown in the brain reduced ceramide generation and attenuated brain ischemic damage with astrocyte inactivation. As expected, Sptlc2 deficiency effectively blocked cGAS/STING pathway-dependent interferon responses. Together, these findings suggest a new therapeutic strategy for pharmacological intervention to attenuate neuroinflammation.PMID:39956315 | DOI:10.1016/j.metabol.2025.156161

Food Chem. 2025 Feb 11;475:143316. doi: 10.1016/j.foodchem.2025.143316. Online ahead of print.ABSTRACTAll the fruits that are or were green accumulate phyllobilins, which are the terminal chlorophyll catabolites. Phyllobilins are part of our daily diet, however, only a few structures have been identified in edible species. To unravel the phyllobilin biosynthetic pathway in fruits, a robust database with 956 phyllobilins was built and taking advantage of our metabolomic approach, three new phyllobilins were identified in melon fruits. Two of them were hydroxylated, an unprecedented biosynthetic pattern in fruits. Even more, one phyllobilin was dihydroxylated for the first time, and the other phyllobilin was a hydroxylated YCC. The third new phyllobilin identified in melon fruits was a pyro-phyllobilin, a long-sought structure that has been kept elusive until now. Therefore, two new biochemical pathways are unravelled to complement the current knowledge of the chlorophyll degradation pathway. Three new phyllobilins with potential health properties also increase the pool of phytochemicals in edible fruits.PMID:39956062 | DOI:10.1016/j.foodchem.2025.143316

Food Chem. 2025 Feb 13;475:143281. doi: 10.1016/j.foodchem.2025.143281. Online ahead of print.ABSTRACTMicrogreens constitute ready-to-eat functional foods, being rich sources of phytonutrients and phytochemicals. Because of their short life cycle, seed priming is a promising strategy to fortify their functional outcome. Vermicompost was applied as seed priming agent for four Brassicaceae microgreens of nutritional interest. The combination of untargeted metabolomics and in vitro assays highlighted the involvement of phenolics and glucosinolates in the functional traits of microgreens, following species-specific responses. Cress accumulated specific polyphenols at low vermicompost dosage, while daikon mainly accumulated aliphatic glucosinolates. Mustard and red cabbage were found to repress glucosinolate accumulation while eliciting polyphenols following vermicompost fortification. The application of machine learning chemometrics revealed that both families of compounds coordinated the functionality of microgreens in terms of antioxidant and neuroprotective bioactivities, highlighting the importance of optimizing genotype-specific interventions. This research sheds light on nutritional enhancement of functional foods, paving the way toward the establishment of novel sustainable food systems.PMID:39956059 | DOI:10.1016/j.foodchem.2025.143281

Food Chem. 2025 Feb 13;476:143405. doi: 10.1016/j.foodchem.2025.143405. Online ahead of print.ABSTRACTTo elucidate the effects of compound curing agent on the microbial community and metabolite composition of Nuodeng ham. The microbial community and small molecule metabolites of Nuodeng ham were analyzed using high-throughput sequencing and UPLC-QE-MS technology in this study. Staphylococcus, Acinetobacter, and Lactobacillus were found to be the dominant bacterial genera in Nuodeng ham. The compound curing agent promoted the formation of L-proline, phenylalanine, L-aspartic acid, and taurine. Through correlation analysis, it was found that Staphylococcus was positively correlated with L-proline and phenylalanine, while Acinetobacter was positively correlated with taurine. This study provides scientific theoretical support for compound curing agents, as well as insight into Nuodeng ham quality.PMID:39956020 | DOI:10.1016/j.foodchem.2025.143405

J Hazard Mater. 2025 Feb 13;489:137613. doi: 10.1016/j.jhazmat.2025.137613. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS), including perfluorooctane sulfonate and perfluorooctanoic acid, are associated with adverse human effects. However, few studies have assessed the effects of PFAS mixtures on hepatocellular carcinoma (HCC). In this study, we systematically investigated the effects and underlying mechanisms of PFAS mixtures on the proliferation, migration, and invasion of HCC cells (JHH-7 and Li-7) in vitro using a combination of biological techniques and high-coverage untargeted metabolomics. A six day exposure to a 5 μM PFAS mixture significantly enhanced the malignant progression of HCC in vitro. Metabolomic analysis identified the upregulation of prostaglandin E2 (PGE2) as a key factor associated with these effects. This hypothesis was further validated using celecoxib, a PGE2 inhibitor, which reduced PGE2 levels in HCC cells, consequently slowing their migration and invasion. Additionally, mice treated with celecoxib exhibited reduced tumor volumes compared with those treated with PFAS alone. These results suggest that PFAS exposure enhances HCC malignancy through the PI3K/AKT signaling pathway via increased PGE2 production. In conclusion, a 5 μM PFAS mixture accelerates HCC proliferation and invasion; moreover, celecoxib demonstrates potential as a therapeutic agent that inhibits these effects.PMID:39955994 | DOI:10.1016/j.jhazmat.2025.137613

Microbiol Res. 2025 Feb 13;294:128100. doi: 10.1016/j.micres.2025.128100. Online ahead of print.ABSTRACTExploring natural antiphotoaging agents is highly desirable. Bifidobacterium longum subsp. iuvenis (Bl. iuvenis) is a newly identified subspecies found in the intestines of infants, and its functions, components and metabolites have not yet been fully elucidated. Here, we demonstrated that Bl. iuvenis YSG is highly efficient in reducing UVB-induced melanin production in melanocytes. Through differential metabolomics analysis, we identified the metabolites 5-hydroxyindole-2-carboxylic acid and aconitic acid as Bl. iuvenis YSG-specific anti-melanogenic substances. Bl. iuvenis YSG potently inhibited melanogenesis by downregulating melanogenic enzymes and directly acting on tyrosinase active sites. Furthermore, B. longum inhibited ROS generation in keratinocytes through its metabolite glycolic acid, increasing the levels of elastin, collagen III and collagen XVII in fibroblasts. We demonstrated that Bl. iuvenis YSG-derived fermentation components not only reduced the number of sunburn cells in UV-irradiated reconstituted human epidermis but also ameliorated ECM damage and epidermal atrophy in ex vivo human epidermis. Our results suggest that mixed metabolites derived from Bl. iuvenis synergistically contribute to antiphotoaging effects, specifically through the production of specific organic acids. These findings revealed that Bl. iuvenis is a novel potential protective agent for photoaging and provided an in-depth study of the underlying mechanism.PMID:39955985 | DOI:10.1016/j.micres.2025.128100

Mar Pollut Bull. 2025 Feb 15;213:117680. doi: 10.1016/j.marpolbul.2025.117680. Online ahead of print.ABSTRACTThis study aimed to elucidate the regulatory mechanisms underlying the toxic effects of glyphosate (GLY) on rainbow clam (M. iridescens), with implications for their culture and conservation. GLY residues in aquatic systems raise significant environmental and public health concerns, yet the underlying mechanisms remain largely elusive. In this study, M. iridescens were acutely exposed to GLY at various concentrations (0, 2.34, 5.45, 12.74, 29.74, and 69.46 mg/L) for 7 days. Gill and hepatopancreas samples were collected to assess oxidative stress status and histopathological examination. Additionally, three concentration groups low concentration (LC) group at 2.34 mg/L, medium concentration (MC) group at 12.74 mg/L, and high concentration (HC) group at 69.46 mg/L were selected for metabolomic analysis. The findings indicated that GLY exposure led to oxidative stress and structural changes in tissues. The metabolomic analysis suggested that GLY exposure exacerbates inflammatory responses and disrupts endocrine function, and sex hormones.PMID:39955984 | DOI:10.1016/j.marpolbul.2025.117680

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Feb 10;1255:124519. doi: 10.1016/j.jchromb.2025.124519. Online ahead of print.ABSTRACTThe bacterial composition of the gut has been found to affect many diseases, including several gastrointestinal cancers. The microbiome appears central in the production of certain metabolites that enter circulation, especially those from bile acids and the essential amino acid tryptophan. The tumor-microenvironment may also produce changes in metabolites, such as those from the tryptophan-kynurenine pathway, of which several compounds may be measured in the blood. As data emerges from large scale metabolomics studies, there will be a need to validate metabolomic biomarkers to confirm their clinical utility. This task also requires knowledge about biological variation of the same metabolites in a healthy population. For this purpose, a novel method was developed for quantification of bile acids and tryptophan metabolites in samples of human serum by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Salting-out assisted liquid-liquid extraction was optimized with the ion-pairing reagent trifluoroacetic acid. In this way, both polar tryptophan metabolites and non-polar bile acids could be extracted with a high recovery, favorable matrix effects, and improved chromatographic focusing, by using straightforward robot pipetting. The instrumental analysis was fast (4 min and 32 s) and with sample injections done directly from the extraction microplate. The method was applied to quantify metabolites in serum from healthy probands, and for investigating inter- and intraindividual variations over six hours.PMID:39955961 | DOI:10.1016/j.jchromb.2025.124519

Ultrason Sonochem. 2025 Feb 12;114:107271. doi: 10.1016/j.ultsonch.2025.107271. Online ahead of print.ABSTRACTJavanese turmeric (Curcuma xanthorrhiza Roxb.) is known for its diverse pharmacological activities due to its rich phytoconstituents, including curcuminoids and xanthorrhizol. Typically, these compounds are extracted using organic solvents, which pose health and environmental risks. Therefore, safer and more environmentally friendly green extraction methods are being developed. This study investigated the effect of ultrasound-assisted extraction (UAE) combined with natural deep eutectic solvents (NADES) based on choline chloride and organic acids (lactic, malic, and citric acid) to find the best combination for extracting curcuminoids and xanthorrhizol from Javanese turmeric. Results showed that UAE using choline chloride and malic acid (1:1) (ChCl-MA) yielded the best results. The Box-Behnken Design optimized water addition, solvent-to-powder ratio, and extraction time, with optimal conditions being 25 % water addition, a 20 mL/g ratio, and a 15-minute extraction time. This method yielded 4.58 mg/g of curcuminoids and 12.93 mg/g of xanthorrhizol. Furthermore, the ChCl-MA NADES with UAE extraction showed more cytoselective activity towards the HeLa cancer cell line compared to the non-cancer HaCaT cell line. In contrast, traditional ethanol extraction was non-selective, as indicated by similar cell viability reductions in both HeLa and HaCaT cells at 6.25 ppm. Collectively, this study is the first to report the optimal NADES combination with UAE, based on salts and organic acids, for the extraction of Javanese turmeric rhizomes with selective cytotoxic effects against cancer cells. These findings may contribute to the development of novel, naturally derived anticancer agents using green extraction techniques.PMID:39955874 | DOI:10.1016/j.ultsonch.2025.107271

Phytomedicine. 2025 Feb 7;139:156453. doi: 10.1016/j.phymed.2025.156453. Online ahead of print.ABSTRACTBACKGROUND: Neurodegenerative disorders, such as Alzheimer's disease (AD), are characterized by a progressive decline in cognitive function. Modulating microglial metabolic reprogramming presents a promising therapeutic avenue for AD. Previous studies have shown that Zexie Tang (ZXT) possesses neuroprotective properties and can ameliorate cognitive impairment, but the underlying mechanisms remain unclear.PURPOSE: This study aimed to investigate the efficacy of ZXT in improving cognitive function in AD mice using a multi-omics approach and to explore its potential role in modulating microglial metabolic reprogramming.METHODS: Behavioral assessments were conducted to evaluate the effects of ZXT on cognitive function in APP/PS1 mice. H&E, Nissl, and Thioflavin S staining were performed to assess the impact of ZXT on brain pathology. A multi-omics approach, including transcriptomics, gut microbiota analysis, and metabolomics, was employed to elucidate the mechanisms of action of ZXT. RT-qPCR, immunoblotting, and immunofluorescence were used to validate the effects of ZXT on glycolipid metabolism, neuroinflammation, and the AMPK-mTOR-HIF1α pathway.RESULTS: ZXT effectively protected against cognitive deficits, reduced hippocampal neuronal apoptosis, and decreased Aβ plaque deposition. Transcriptomics analysis revealed that ZXT was involved in immune system processes and metabolic processes and had a specific cellular response with microglia. Additionally, ZXT regulated the composition and functions of brain metabolites and gut microbiota. Our study demonstrated that ZXT positively influenced glucolipid metabolism and attenuated neuroinflammation, which were linked to the AMPK-mTOR-HIF1α pathway in the brain.CONCLUSION: Our findings suggested that ZXT may mitigate cognitive deficits in APP/PS1 mice by modulating gut microbiota and enhancing brain energy metabolism. ZXT regulated glucolipid metabolism and neuroinflammation by modulating microglial metabolic reprogramming involving the AMPK-mTOR-HIF1α pathway.PMID:39955825 | DOI:10.1016/j.phymed.2025.156453

Plant Physiol Biochem. 2025 Feb 11;221:109633. doi: 10.1016/j.plaphy.2025.109633. Online ahead of print.ABSTRACTSelenium (Se) is a vital trace element for human health, and its uneven distribution in soil triggers Se deficiencies in some regions. Se biofortification has been demonstrated to mitigate this issue by producing Se-enriched crops. Chives (Allium schoenoprasum cv. 'sijixiaoxiangcong'), a simple-to-cultivate and fast-growing vegetable, offers a promising Se-accumulation ability. However, the physiological and molecular mechanisms underlying Se responses in chives remain unclear. This study applied sodium selenite at various doses to chives via root irrigation, and integrated strategies including multi-omics were employed to unfold the response mechanism. (1) Physiological data reveal that sodium selenite irrigation adversely affects the height, shoot weight, chlorophyll, and soluble sugar content of chives' aerial parts. However, chives exhibit a remarkable ability to accumulate selenium, reaching up to 40.21 mg kg-1 DW under high Se exposure (160 mg L-1); (2) Transcriptomic analysis revealed significant enrichment of the phenylpropanoid biosynthesis and plant hormone signal transduction pathways under Se treatment. Key DEGs, such as MAPKKK17_18, JAZs, and PCL, were identified as Se response candidates. Our findings show that selenomethionine is the primary form of Se accumulation, and DEGs linked to antioxidant defense and phenylpropanoid biosynthesis are crucial for mitigating Se stress; (3) Importantly, plant hormone signaling plays a central role by regulating phenylpropanoid metabolism and enhancing the antioxidant enzyme system, highlighting its significance in chives' Se tolerance. These results clarify the Se response mechanisms in chives and enable Se-enriched chive cultivation.PMID:39955822 | DOI:10.1016/j.plaphy.2025.109633

Brief Bioinform. 2024 Nov 22;26(1):bbaf059. doi: 10.1093/bib/bbaf059.ABSTRACTPregnancy is a vital period affecting both maternal and fetal health, with impacts on maternal metabolism, fetal growth, and long-term development. While the maternal metabolome undergoes significant changes during pregnancy, longitudinal shifts in maternal urine have been largely unexplored. In this study, we applied liquid chromatography-mass spectrometry-based untargeted metabolomics to analyze 346 maternal urine samples collected throughout pregnancy from 36 women with diverse backgrounds and clinical profiles. Key metabolite changes included glucocorticoids, lipids, and amino acid derivatives, indicating systematic pathway alterations. We also developed a machine learning model to accurately predict gestational age using urine metabolites, offering a non-invasive pregnancy dating method. Additionally, we demonstrated the ability of the urine metabolome to predict time-to-delivery, providing a complementary tool for prenatal care and delivery planning. This study highlights the clinical potential of urine untargeted metabolomics in obstetric care.PMID:39955767 | DOI:10.1093/bib/bbaf059

BMC Plant Biol. 2025 Feb 15;25(1):206. doi: 10.1186/s12870-025-06219-0.ABSTRACTBACKGROUND: Polyphyllins are significant medicinal compounds found in Paris species, with different polyphyllins fulfilling distinct medicinal roles. Although some genes involved in polyphyllin synthesis have been identified, further exploration of the genes in the polyphyllin synthesis pathway is necessary due to the extensive genome of Paris species. The content and composition of polyphyllins vary among different Paris species, and the variations in specific polyphyllin levels across these plants make them promising candidates for identifying metabolites and genes associated with the biosynthesis of specific polyphyllins.RESULTS: In this study, we investigate the global metabolic and transcriptomic profiles of three types of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz, one Paris fargesii Franch, and one Paris forrestii (Takht.) H. Li. The rhizome of P. polyphylla is rich in polyphyllin I and II, while P. forrestii is abundant in polyphyllin III, and P. fargesii contains high levels of polyphyllin VI, VII and H. The three Paris species exhibit distinct metabolomic and transcriptomic profiles. Through an integrated analysis of metabolic and transcriptomic data, along with a phylogenetic analysis of genes related to polyphyllin synthesis in Paris, we annotated a total of six 2,3-oxidosqualene cyclases (OSCs), 120 cytochrome P450s (CYPs), and 138 UDP glycosyltransferases (UGTs). Phylogenetic tree analysis of the obtained data assisted in refining the candidate gene pool for OSC, CYP, and UGT. Subsequently, we identified 6, 12, and 26 candidate genes for OSC, CYP, and UGT, respectively. Finally, by combining the analyses of metabolic and genetic differences, we identified a total of 17 candidate genes, including 2 CAS, 4 CYP, and 11 UGT.CONCLUSIONS: P. fargesii and P. forrestii are candidate medicinal plants for the development and application of specific polyphyllins. Transcripts from the UGT91 subfamily in Paris may play dual roles, contributing to both the synthesis of polyphyllin II and the catabolism of polyphyllin V and VI. The homologous genes of PpUGT73CE1 may regulate the synthesis of polyphyllin VI in P. fargesii. This study provides new insights into the investigation of biosynthetic pathways in medicinal plants that lack gene clusters.PMID:39955498 | DOI:10.1186/s12870-025-06219-0