PubMed

Plant Physiol Biochem. 2025 Mar 18;223:109802. doi: 10.1016/j.plaphy.2025.109802. Online ahead of print.ABSTRACTDrought stress (DS) significantly hampers the growth and productivity of tea plants, necessitating effective strategies to enhance their resilience. This study comprehensively investigated the mechanisms of carbonyl volatiles-methyl jasmonate (MeJA) and cis-3-hexenyl acetate (cis-3-HAC) and signal peptide CLAVATA3/EMBRYO-SURROUNDING REGION-RELATED 25 (CLE25) promotion DS resistance using integrative metabolomics and proteomics strategy. Total pigment content decreased, while soluble sugar and proteins increased significantly under DS and further increased after foliar inducement of CLE25, MeJA, and cis-3-HAC. Gallated catechins and amino acids exhibited apparent decreased under DS, especially EGCG (24.6-13.4 mg g-1) and theanine (10.66-3.78 mg g-1), but significantly mitigated by CLE25 inducement. Antioxidant enzymes activity, such as catalase (CAT), jumped from 23.1 to 48.2 and further boosted to 118.8 Ug-1min-1 FW with CLE25. Proteomic analysis revealed massive increased in stress tolerance proteins, particularly dehydrins and heat shock proteins, rising by >50.0 % with CLE25 inducement and the expression levels of peroxidase (POX), superoxide dismutase (SOD), α-galactosidase (α-GAL), carboxypeptidases (CPs), and transaldolase (TAL) exhibited higher after inducement. Furthermore, stress signaling-related proteins were in-depth explored, especially thioredoxin proteins; sucrose non-fermenting 1-related protein kinase 2 (SnRK2) was novelly verified in activating abscisic acid (ABA) responding. Differences among drought resistance mechanisms after carbonyl volatile and CLE25 treatments were comprehensively studied. The integration of metabolite and protein levels provided a comprehensive illustration of tea DS tolerance mechanisms and offered promising promotion strategies through foliar application of MeJA, cis-3-HAC, and CLE25.PMID:40174298 | DOI:10.1016/j.plaphy.2025.109802

Nat Prod Res. 2025 Apr 2:1-10. doi: 10.1080/14786419.2025.2487692. Online ahead of print.ABSTRACTDuchesnea indica is a traditional medicinal plant known for its antioxidant, anticancer and antibacterial properties. This study is the first to investigate endophytic fungi in D. indica, isolating PS4 (Aspergillus sp.) and employing the innovative OSMAC strategy to enhance its metabolomic profile, analysing the metabolites of both D. indica and its endophytic fungus for the first time using UPLC-Orbitrap HRMS. Specifically, in potato dextrose broth (PDB), PS4's metabolites showed remarkable potential for antioxidant, antibacterial and anticancer effects. The potential targets for the anticancer effects of D. indica and its endophytic fungus were innovatively predicted using network pharmacology and molecular docking, identifying 17 key compounds and six core target genes for the first time in this context. Strong binding between these components and target genes underscores the value of integrating metabolomics and network pharmacology in natural product research, laying a foundation for future drug development.PMID:40174222 | DOI:10.1080/14786419.2025.2487692

Plant Physiol. 2025 Apr 2:kiaf126. doi: 10.1093/plphys/kiaf126. Online ahead of print.ABSTRACTPotato (Solanum tuberosum) is highly water and space efficient but susceptible to abiotic stresses such as heat, drought, and flooding, which are severely exacerbated by climate change. Our understanding of crop acclimation to abiotic stress, however, remains limited. Here, we present a comprehensive molecular and physiological high-throughput profiling of potato (Solanum tuberosum, cv. Désirée) under heat, drought, and waterlogging applied as single stresses or in combinations designed to mimic realistic future scenarios. Stress responses were monitored via daily phenotyping and multi-omics analyses of leaf samples comprising proteomics, targeted transcriptomics, metabolomics, and hormonomics at several timepoints during and after stress treatments. Additionally, critical metabolites of tuber samples were analyzed at the end of the stress period. We performed integrative multi-omics data analysis using a bioinformatic pipeline that we established based on machine learning and knowledge networks. Waterlogging produced the most immediate and dramatic effects on potato plants, interestingly activating ABA responses similar to drought stress. In addition, we observed distinct stress signatures at multiple molecular levels in response to heat or drought and to a combination of both. In response to all treatments, we found a downregulation of photosynthesis at different molecular levels, an accumulation of minor amino acids, and diverse stress-induced hormones. Our integrative multi-omics analysis provides global insights into plant stress responses, facilitating improved breeding strategies toward climate-adapted potato varieties.PMID:40173380 | DOI:10.1093/plphys/kiaf126

Curr Opin Organ Transplant. 2025 Apr 3. doi: 10.1097/MOT.0000000000001217. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Despite the introduction of many new immunosuppressive medications, allograft rejection remains a significant complication in transplantation. The use of "liquid biopsy" to evaluate allograft function and detect early rejection has recently become a prominent focus of investigation as it holds promise in providing noninvasive and immediate insights into the cellular and molecular makeup of the graft.RECENT FINDINGS: In recent years, the introduction of molecular medicine along with the use of new technologies, including high-throughput techniques, has not only accelerated biomarker discovery but has also contributed to improving our understanding of the mechanisms underlying immune rejection. Genomics, transcriptomics, and metabolomics approaches, along with the increasing use of machine learning techniques, have paved the way for the discovery and development of novel biomarkers.SUMMARY: Each year, there are hundreds of new biomarker discoveries in the publications. However, only a small fraction can be practically used as clinical tests or surrogate endpoints, receive FDA approval, and reach clinical application. Well designed and reproducible discovery and validation studies are rare and crucial. A contributing factor could be poor study design or quality of biospecimen repositories. In this review, we discuss urinary biomarkers of kidney allograft rejection that have shown promising findings but have yet to be successfully transitioned from bench to bedside.PMID:40173008 | DOI:10.1097/MOT.0000000000001217

Mycorrhiza. 2025 Apr 2;35(2):26. doi: 10.1007/s00572-025-01188-6.ABSTRACTLike other plant-microbe symbioses, the establishment of orchid mycorrhiza (ORM) is likely to require specific communication and metabolic adjustments between the two partners. However, while modulation of plant and fungal metabolism has been investigated in fully established mycorrhizal tissues, the molecular changes occurring during the pre-symbiotic stages of the interaction remain largely unexplored in ORM. In this study, we investigated the pre-symbiotic responses of the ORM fungus Tulasnella sp. SV6 to plantlets of the orchid host Serapias vomeracea in a dual in vitro cultivation system. The fungal mycelium was harvested prior to physical contact with the orchid roots and the fungal transcriptome and metabolome were analyzed using RNA-seq and untargeted metabolomics approaches. The results revealed distinct transcriptomic and metabolomic remodelling of the ORM fungus in the presence of orchid plantlets, as compared to the free-living condition. The ORM fungus responds to the presence of the host plant with a significant up-regulation of genes associated with protein synthesis, amino acid and lipid biosynthesis, indicating increased metabolic activity. Metabolomic analysis supported the RNA-seq data, showing increased levels of amino acids and phospholipids, suggesting a remodelling of cell structure and signalling during the pre-symbiotic interaction. In addition, we identified an increase of transcripts of a small secreted protein that may play a role in early symbiotic signalling. Taken together, our results suggest that Tulasnella sp. SV6 may perceive information from orchid roots, leading to a readjustment of its transcriptomic and metabolomic profiles.PMID:40172721 | DOI:10.1007/s00572-025-01188-6

Anal Bioanal Chem. 2025 Apr 2. doi: 10.1007/s00216-025-05861-9. Online ahead of print.ABSTRACTData-independent acquisition (DIA) and data-dependent acquisition (DDA) are frequently employed in the execution of tandem mass spectrometry (MS2) analyses. This study explored the application of DIA (MSe) and DDA (fast-DDA) in liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics using Panax genus samples. MSe provided comprehensive sample information, extracting more ion peaks with better peak shape and increased scan points compared to fast-DDA. Features from MSe data are four times more than those from fast-DDA data. Fast-DDA, however, delivered high-quality MS2 data, enhancing compound annotation via the GNPS web tool. Database matches with fast-DDA data were nearly 35 times greater than those using MSe data. Therefore, combining MSe and fast-DDA can improve data analysis and metabolite annotation. An improved workflow integrating DIA and DDA was proposed, requiring additional QC sample injections for DDA analysis but eliminating the need for sample reprocessing and re-analysis, thus saving time and resources. The established workflow was applied to the Panax genus samples analysis to confirm its applicability. This study offers a deeper understanding of DIA and DDA, guiding the selection of data acquisition strategies for LC-MS-based untargeted metabolomics.PMID:40172670 | DOI:10.1007/s00216-025-05861-9

Eur J Nutr. 2025 Apr 2;64(4):144. doi: 10.1007/s00394-025-03660-7.ABSTRACTPURPOSE: Our aim was to examine the effects of combined prebiotic fiber supplementation and weight loss counseling on liver fat, body composition, subjective appetite, serum metabolomics, and intestinal microbiota in adults with MASLD.METHODS: In a double blind, placebo-controlled trial, adult participants aged 18-70 years old with MASLD were randomized to receive prebiotic (oligofructose-enriched inulin, 16 g/day; n = 22) or isocaloric placebo (maltodextrin; n = 20) for 24 weeks alongside weight loss counseling from a registered dietitian. Primary outcomes were change in intrahepatic fat % (IHF%) and hepatic injury from baseline to 24 weeks. Secondary outcomes included body composition, subjective appetite, serum lipids and cytokines, fecal microbiota, and serum metabolomics.RESULTS: At baseline, participants had IHF of 14.4 ± 8.4%. The change in IHF from baseline to 24 weeks did not differ between prebiotic and placebo. Prebiotic participants had a greater decrease (p = 0.029) in percent trunk fat compared to placebo. Compared to placebo, prebiotic significantly decreased desire to eat and hunger ratings over the course of the intervention. Fecal microbiota analysis showed a significant increase in Bifidobacterium abundance with prebiotic. A pathway analysis based on untargeted serum metabolomics revealed a downregulation of taurine and hypotaurine metabolism in the placebo group which was conserved in the prebiotic group.CONCLUSION: Adding prebiotic fiber supplementation to weight loss counseling for adults with MASLD enhanced reductions in trunk fat and had a beneficial effect on subjective appetite compared to placebo. Improvements in fecal microbial profile and taurine metabolism revealed specific beneficial effects of prebiotics in the management of MASLD.CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov/study/NCT02568605.PMID:40172664 | DOI:10.1007/s00394-025-03660-7

Anal Chem. 2025 Apr 2. doi: 10.1021/acs.analchem.5c00157. Online ahead of print.ABSTRACTSpatial metabolomics based on mass spectrometry imaging (MSI) is a promising approach for fundamental biological research and disease biomarker discovery. It simultaneously reveals the spatial distributions of hundreds of metabolites across tissue sections. While previous MSI experiments predominantly rely on high-resolution mass analysis for metabolite annotation, the high specificity in resolving molecular structures is essential to distinguish isomers or isobars to obtain ultimate identities of the metabolites. This is also critical for correlating their biological functions with spatial distribution patterns. Tandem mass spectrometry (MS/MS) is effectively used to obtain molecular structural information and has been integrated into MSI for spatial mapping of structurally distinct biomolecules, though typically with low coverage. The main technical challenge in achieving high-coverage, high-structure-resolving spatial mapping of biomolecules lies in the limited amount of sample available from each tissue pixel in conventional MS/MS analysis, which restricts the number of MS/MS scans that can be conducted on the metabolite precursors of interest. In this Perspective, we highlight recent developments in advanced MS/MS imaging strategies aimed at achieving high-coverage spatial metabolomics.PMID:40172484 | DOI:10.1021/acs.analchem.5c00157

mSphere. 2025 Apr 2:e0101124. doi: 10.1128/msphere.01011-24. Online ahead of print.ABSTRACTThe obligate intracellular parasite Toxoplasma gondii replicates within a specialized compartment called the parasitophorous vacuole (PV). Recent work showed that despite living within a PV, Toxoplasma endocytoses proteins from the cytosol of infected host cells via a so-called ingestion pathway. The ingestion pathway is initiated by dense granule protein GRA14, which binds host endosomal sorting complex required for transport (ESCRT) machinery to bud vesicles into the lumen of the PV. The protein-containing vesicles are internalized by the parasite and trafficked to the plant vacuole-like compartment (PLVAC), where cathepsin protease L (CPL) degrades the cargo, and the chloroquine resistance transporter (CRT) exports the resulting peptides and amino acids to the parasite cytosol. However, although the ingestion pathway was proposed to be a conduit for nutrients, there is limited evidence for this hypothesis. We reasoned that if Toxoplasma uses the ingestion pathway to acquire nutrients, then parasites lacking GRA14, CPL, or CRT should rely more on biosynthetic pathways or alternative scavenging pathways. To explore this, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen in wild-type (WT) parasites and Δgra14, Δcpl, and Δcrt mutants to identify genes that become more fitness conferring in ingestion-deficient parasites. Our screen revealed a significant overlap of genes that potentially become more fitness conferring in the ingestion mutants compared to WT. Pathway analysis indicated that Δcpl and Δcrt mutants relied more on pyrimidine biosynthesis, fatty acid biosynthesis, tricarboxylic acid (TCA) cycle, and lysine degradation. Bulk metabolomic analysis showed reduced levels of glycolytic intermediates and amino acids in the ingestion mutants compared to WT, highlighting the pathway's potential role in host resource scavenging. Interestingly, Δcpl and Δcrt showed an exacerbated growth defect when cultured in amino acid-depleted media, suggesting that disrupting proteolysis or the export of proteolytic products from the PLVAC affects parasite survival during nutrient scarcity.IMPORTANCE: Toxoplasma gondii is an obligate intracellular pathogen that infects virtually any nucleated cell in most warm-blooded animals. Infections are asymptomatic in most cases, but people with weakened immunity can experience severe disease. For the parasite to replicate within the host, it must efficiently acquire essential nutrients, especially as it is unable to make several key metabolites. Understanding the mechanisms by which Toxoplasma scavenges nutrients from the host is crucial for identifying potential therapeutic targets. Our study suggests that the ingestion pathway contributes to sustaining parasite metabolites and parasite replication under amino acid-limiting conditions. This work advances our understanding of the metabolic adaptability of Toxoplasma.PMID:40172222 | DOI:10.1128/msphere.01011-24

Gut Microbes. 2025 Dec;17(1):2486511. doi: 10.1080/19490976.2025.2486511. Epub 2025 Apr 2.ABSTRACTAging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.PMID:40172215 | DOI:10.1080/19490976.2025.2486511

Clin Exp Dent Res. 2025 Feb;11(1):e70095. doi: 10.1002/cre2.70095.ABSTRACTOBJECTIVES: This study aims to summarize recent studies available on untargeted metabolomics employed for periodontitis diagnosis, from saliva and gingival crevicular fluid samples, to identify recurring metabolites with biomarker-value potential. A secondary objective was to analysudurue the protocols of existing studies, to facilitate further research.MATERIAL AND METHODS: Three databases were electronically searched for relevant studies (PubMed, Web of Science, Scopus). Risk of bias assessment was performed using the Newcastle-Ottawa scale (NOS). Data was extracted from studies, regarding general characteristics and conclusions, population characteristics, periodontal protocols, and metabolomics protocols. Metabolic pathway analysis was performed for recurrent metabolites.RESULTS: After screening 405 studies, 13 studies (10 using saliva samples, 3 using GCF samples) were included. 22 metabolites were identified in more than one study and included into the pathway analysis. Butyrate, lactate, isoleucine, glucose, pyruvate, isovalerate, hypoxanthine/xanthine, proline, valine, phenylalanine, and ethanol were most frequently encountered and were found upregulated in periodontitis patients compared to periodontally healthy patients.CONCLUSIONS: Metabolomics could provide valuable opportunities in validating potential biomarkers or diagnosis panels, contributing to the screening, prognosis, progression and monitoring of periodontitis. Further studies on larger populations and using established protocols are needed. (PROSPERO CRD42023470339).PMID:40172143 | DOI:10.1002/cre2.70095

Int J Dev Biol. 2025 Mar 25. doi: 10.1387/ijdb.240147me. Online ahead of print.ABSTRACTIntrauterine growth restriction (IUGR) is increasingly recognized as a significant risk factor for metabolic disorders in adulthood. Employing a multi-faceted approach encompassing histopathological, immunohistochemical, biochemical, Western-blotting, and metabolomics analyses, this study aimed to elucidate potential metabolite markers of IUGR, and catch-up growth-related metabolic disturbances and the underlying metabolic pathways implicated in IUGR pathogenesis. This study cohort comprised 54 male siblings from 20 Sprague-Dawley female young rats. On the 19th day of gestation, half of the pregnant rats underwent bilateral uterine artery ligation, while the remaining half underwent a simulated surgical intervention involving solely peritoneal incisions. Blood and liver samples were collected from the pups after attaining catch-up growth at the postnatal weeks 2, 4, and 8. IUGR rats exhibited a spectrum of changes including histological abnormalities, altered apoptosis rates, oxidative stress markers, and mitochondrial energy metabolism. Metabolomic analysis revealed dysregulation in multiple metabolic pathways encompassing galactose, propanoate, glycerolipid, cysteine, methionine, and tyrosine metabolism, among others. Notably, disturbances were observed in butanoate, glutathione metabolism, valine, leucine, and isoleucine biosynthesis and degradation, citrate cycle, aminoacyl-tRNA biosynthesis, as well as glycolysis/gluconeogenesis. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, heart failure, cancer, mental retardation, kidney and liver diseases, and cataracts. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies aimed at mitigating the risk of metabolic diseases in individuals with a history of IUGR.PMID:40172029 | DOI:10.1387/ijdb.240147me

J Med Virol. 2025 Apr;97(4):e70304. doi: 10.1002/jmv.70304.ABSTRACTThe human oral cavity contains highly diverse microbes, including bacteria, fungi, and viruses. Human herpesviruses are ubiquitous pathogens, and the oral cavity is conducive to the replication, dissemination, and pathogenesis of human herpesviruses. Herpesviruses are generally pathogenic in immunodeficient individuals, such as AIDS patients and organ transplant recipients. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma and two types of rare lymphoma, that is, primary effusion lymphoma and multicentric Castleman's disease. Mounting evidence indicates that KSHV viral load positively correlates with ongoing bacterial infection in the oral cavity, suggesting that bacteria potentially stimulate KSHV replication. However, the mechanism by which oral bacteria may promote KSHV lytic replication is poorly understood. In this study, we performed DNA sequencing and 16S ribosomal RNA analysis of saliva samples of AIDS-KS patients. A correlation analysis identified a panel of oral residential bacteria and uncommon ones that paralleled with KSHV viral load. Performing functional assays, we discovered that the sexually transmitted Neisseria gonorrhoeae (N.g.) significantly increased KSHV lytic replication. Increased KSHV lytic replication was evidenced by elevated levels of mRNA and proteins of viral lytic genes. N.g. stimulation increases the expression of RTA that drives viral lytic replication. Metabolomic analysis reveals the synergistic effect of KSHV and N.g. on cellular metabolism, including the glycolysis and purine and pyrimidine synthesis, that likely underpins the elevated KSHV lytic replication. Findings from our study shed light on the molecular detail of bacteria-virus interaction in the oral cavity and provide references to develop an innovative strategy to treat diseases associated with KSHV.PMID:40171956 | DOI:10.1002/jmv.70304

Diabetes Obes Metab. 2025 Apr 2. doi: 10.1111/dom.16351. Online ahead of print.ABSTRACTAIMS: To identify hub metabolic biomarkers that constructively shape the type 2 diabetes mellitus (T2DM) risk network.MATERIALS AND METHODS: We analysed data from 98 831 UK Biobank participants, confirming T2DM diagnoses via medical records and International Classification of Diseases codes. Totally 168 circulating metabolites were quantified by nuclear magnetic resonance at baseline. Metabolome-wide association studies with Cox proportional hazards models were performed to identify statistically significant metabolites. Network analysis was applied to compute topological attributes (degree, betweenness, closeness and eigencentrality) and to detect small-world features (high clustering, short path lengths). Identified metabolites were used with XGBoost models to assess risk prediction performance.RESULTS: Over a median 12-year follow-up, 114 metabolites were significantly associated with T2DM risk and clustered into three distinct small-world modules. Total triglycerides and large high-density lipoprotein (HDL) cholesterol emerged as the pivotal biomarkers in the 'risk' and 'protective' modules, respectively, as evidenced by their high eigencentrality. Moreover, total branched-chain amino acids (BCAAs) exhibited small-world network characteristics exclusively in pre-T2DM individuals, suggesting them as a potent early indicators. GlycA demonstrated high closeness centrality in females, implying a female-specific risk biomarker.CONCLUSIONS: By constructing a metabolic network that captures the complex interrelationships among circulating metabolites, our study identified total triglycerides and large HDL cholesterol as central hubs in the T2DM risk metabolome network. BCAA and GlycA emerged as alarm indicators for pre-T2DM individuals and females, respectively. Network analysis not only elucidates the topological functional roles of biomarkers but also addresses the limitations of false positives and collinearity in single-metabolite studies, offering insights for metabolic pathway research and precision interventions.PMID:40171861 | DOI:10.1111/dom.16351

Anal Methods. 2025 Apr 2. doi: 10.1039/d4ay02165g. Online ahead of print.ABSTRACTLung carcinogenesis (LC) is a kind of disease, which threatens human health seriously. Metabolomic research on bio-fluids and tissues is crucial for elucidating the pathogenesis of LC and understanding the therapeutic mechanisms of medicines. In this study, we established a rat model for LC by induction with urethane. The anti-tumor effect of Qi-Yu-San-Long decoction (QYSLD) on LC was assessed through morphology changes, histopathological examination, and inflammation levels. Utilizing the metabolomics technique based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), we investigated the metabolic changes in the plasma and lungs of LC rats and explored the ameliorative effects of QYSLD on the molecular levels. Functional biomarkers associated with QYSLD in LC rats were identified and relatively quantified. The results manifested that, in contrast to the control group, the number of tumor nodules and inflammation levels in the LC model group increased significantly, indicating that the LC rat model was successfully built. After QYSLD treatment, the morphology and lesion degree of LC rats were greatly improved. A total of 23 differential metabolites between the control group and the urethane-induced LC group were screened through plasma and lung tissue metabolomics studies, of which 20 were considerably modulated after QYSLD treatment. Metabolic pathway analysis revealed that the pathogenesis of LC and the therapeutic effects of QYSLD primarily involved glycerophospholipid metabolism, ether lipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism. Our findings provide a potential intracellular metabolite profile for urethane-induced LC and demonstrate that QYSLD exerts anti-tumor effects on LC by modulating multiple metabolic pathways.PMID:40171836 | DOI:10.1039/d4ay02165g

Food Funct. 2025 Apr 2. doi: 10.1039/d5fo00440c. Online ahead of print.ABSTRACTEllagic acid (EA) exhibits protective effects on non-alcoholic fatty liver disease (NAFLD). However, the ability to produce urolithins and the health benefits associated with EA consumption differ considerably among individuals. Therefore, the different effects of EA on high-fat and high-fructose diet (HFFD)-induced NAFLD, considering variability in urolithin-producing ability, were explored. Our results showed that EA could effectively reduce body weight, lipid accumulation and insulin resistance, and improve oxidative stress and inflammation in NAFLD mice. The metabolomics analysis indicated that liver metabolism disorder induced by HFFD was obviously improved by EA mainly through the regulation of unsaturated fatty acid biosynthesis and amino acid metabolism. In particular, the improvement effect of EA on NAFLD in mice with high urolithin A production was better than that in their low counterparts. Moreover, EA treatment reshaped the gut microbiota imbalance caused by HFFD. Specifically, compared to the model group, the lower abundances of Faecalibaculum (by 95.11%), Ruminococcus_torques_group (by 208.14%), Clostridium_sensu_stricto_1 (by 449.37%), and Ileibacterium (by 172.64%), while higher abundances of Verrucomicrobia and Akkermansia (by 425.0%) were observed in the high-UroA-producing group (p < 0.05). This study provided new insights into EA's anti-NAFLD effectiveness and suggested that the response capacity of the gut microbiota to EA greatly determined the performance of EA in alleviating the development of NAFLD.PMID:40171675 | DOI:10.1039/d5fo00440c

J Asian Nat Prod Res. 2025 Apr 2:1-15. doi: 10.1080/10286020.2025.2481291. Online ahead of print.ABSTRACTSalidroside is a traditional Chinese medicine with multiple pharmacological activities such as anti-inflammatory and antioxidant properties, while acute kidney injury (AKI) is a common sepsis-induced acute inflammatory response. Using transcriptomics combined with metabolomics, this study identifies arachidonic acid metabolism-associated ferroptosis as an important mechanism for salidroside to improve sepsis-induced AKI (SI-AKI).PMID:40171644 | DOI:10.1080/10286020.2025.2481291

iScience. 2025 Mar 3;28(4):112135. doi: 10.1016/j.isci.2025.112135. eCollection 2025 Apr 18.ABSTRACTGlycopeptide antibiotics (GPA) such as vancomycin are essential last-resort antibiotics produced by actinomycetes. Their biosynthesis is encoded within biosynthetic gene clusters, also harboring genes for regulation, and transport. Diverse types of GPAs have been characterized that differ in peptide backbone composition and modification patterns. However, little is known about the ATP-binding cassette (ABC) transporters facilitating GPA export. Employing a multifaceted approach, we investigated the substrate specificity of GPA ABC-transporters toward the type-I GPA balhimycin. Phylogenetic analysis suggested and trans-complementation experiments confirmed that balhimycin is exported only by the related type I GPA transporters Tba and Tva (transporter of vancomycin). Molecular dynamics simulations and mutagenesis experiments showed that Tba exhibits specificity toward the peptide backbone rather than the modifications. Unexpectedly, deletion or functional inactivation of Tba halted balhimycin biosynthesis. Combined with proximity biotinylation experiments, this suggested that the interaction of the active transporter with the biosynthetic machinery is required for biosynthesis.PMID:40171492 | PMC:PMC11960670 | DOI:10.1016/j.isci.2025.112135

JOR Spine. 2025 Mar 31;8(2):e70062. doi: 10.1002/jsp2.70062. eCollection 2025 Jun.ABSTRACTBACKGROUND: Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial socioeconomic impacts. Despite its high prevalence, the pathogenesis of IDD remains unclear, and effective pharmacological interventions are lacking. This study aimed to investigate metabolic alterations in IDD and explore potential therapeutic targets by analyzing lipotoxicity-related mechanisms in nucleus pulposus (NP) cells.METHODS: Metabolomics and magnetic resonance spectroscopy were utilized to profile metabolic changes in NP tissues from advanced-stage IDD. Transcriptomics and metabolomics integration were performed to identify key regulatory pathways. In vitro experiments using human NP cells exposed to palmitic acid were conducted to evaluate endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lipid droplet accumulation, and senescence. Phosphatidylcholine supplementation was tested for its ability to mitigate lipotoxicity, with ER-mitochondria interactions and mitochondrial oxidation capacity assessed as mechanistic endpoints.RESULTS: Our findings revealed an abnormal lipotoxic condition in NP cells from advanced-stage IDD. Furthermore, we identified abnormal accumulation of triglycerides and palmitic acid in NP cells from IDD. The palmitic acid accumulation resulted in endoplasmic reticulum stress, mitochondrial damage, lipid droplet accumulation, and senescence of NP cells. By integrating transcriptomics and metabolomics analyses, we discovered that phosphatidylcholine plays a role in regulating palmitic acid-induced lipotoxicity. Notably, phosphatidylcholine level was found to be low in the endoplasmic reticulum and mitochondria of advanced-stage NP cells. Phosphatidylcholine treatment alleviated palmitic acid-induced lipid droplet accumulation and senescence of NP cells by modulating ER-mitochondria contacts and mitochondrial oxidation capacity.CONCLUSION: Phosphatidylcholine emerges as a potential therapeutic agent to counteract lipotoxic stress by modulating organelle interactions and mitochondrial function. These findings advance our understanding of IDD pathogenesis and provide a novel metabolic target for therapeutic development.PMID:40171442 | PMC:PMC11956213 | DOI:10.1002/jsp2.70062

Front Vet Sci. 2025 Mar 18;12:1528530. doi: 10.3389/fvets.2025.1528530. eCollection 2025.ABSTRACTIn ruminants, conceptus elongation is a crucial developmental process that depends on uterine lumen fluid (ULF) and coincides with a period of high pregnancy loss. Prostaglandins (PGs) play indispensable roles in conceptus elongation and implantation. However, the effects of uterus-derived PGs on the uterine environment remain unclear. To explore the metabolic pathways and metabolites induced by endometrium-derived PGs that may affect conceptus elongation and implantation in dairy cows, we investigated the biochemical composition of ULF following intrauterine perfusion of meloxicam from days 12 to 14 of the estrous cycle. Intrauterine administration of meloxicam significantly downregulated the prostaglandin-related metabolites in the ULF. A total of 385 distinct metabolites, primarily clustered within lipids and lipid-like molecules, organic acids and derivatives, organoheterocyclic compounds, and benzenoids, were identified. The metabolite network analysis identified 10 core metabolites as follows: S-adenosylhomocysteine, guanosine, inosine, thymidine, cholic acid, xanthine, niacinamide, prostaglandin I2, 5-hydroxyindoleacetic acid, and indoleacetaldehyde. The pathway enrichment analysis revealed three significantly altered metabolic pathways: arachidonic acid metabolism, tryptophan (Trp) metabolism, and linoleic acid metabolism. A total of five metabolites-guanosine, inosine, thymidine, butyryl-l-carnitine, and l-carnitine-were associated with attachment and pregnancy loss and could serve as predictors of fertility. This global metabolic study of ULF enhances our understanding of histotroph alternations induced by uterus-derived PGs during diestrus in dairy cows, with implications for improving dairy cow fertility.PMID:40171410 | PMC:PMC11959509 | DOI:10.3389/fvets.2025.1528530