PubMed

Ann Allergy Asthma Immunol. 2025 May;134(5):502-503. doi: 10.1016/j.anai.2025.02.002.NO ABSTRACTPMID:40345713 | DOI:10.1016/j.anai.2025.02.002

RMD Open. 2025 May 8;11(2):e005278. doi: 10.1136/rmdopen-2024-005278.ABSTRACTOBJECTIVES: To identify specific metabolomic profiles associated with gout flares in people with gout.METHODS: Participants with gout were sequentially enrolled. In cross-sectional analysis, data were analysed according to the presence of gout flare (acute group) or absence of gout flare (intercritical group) at the time of enrolment. Participants in the intercritical group were prospectively followed and analysed according to the development of gout flares (recurrent flare group) or no gout flare (no flare group) over 1 year. Relative abundances of metabolites in serum obtained at the baseline visit were measured by untargeted liquid chromatography-mass spectrometry. Risk of incident flare was analysed using least absolute shrinkage and selection operator (LASSO)-Cox regression and time-receiver operating characteristic (ROC). Machine learning models were performed to identify biomarkers in cross-sectional and longitudinal analysis, which was further optimised using quantitative targeted metabolomics in an independent validation cohort.RESULTS: Participants in the acute and intercritical groups showed distinct metabolic profiles, including carbohydrate, lipid and nucleotide metabolism. Many metabolites were associated with recurrent gout flare in the prospective analysis. The metabolic risk score with six LASSO-derived metabolites, including 5-methoxytryptamine, differentiated well for gout flare risk, yielding an area under the ROC curve (AUC) of 0.82 (95% CI 0.74 to 0.90). Machine learning models achieved an AUC of 0.828 for comparison between the acute and intercritical groups. For the prediction of recurrent flare, AUC reached 0.807-0.867 with combined metabolites and clinical measurements.CONCLUSIONS: Metabolic reprogramming differentiates between the acute and intercritical stages of gout, and implicated metabolites may serve as biomarkers for future gout flares.PMID:40345707 | DOI:10.1136/rmdopen-2024-005278

Clin Nutr ESPEN. 2025 May 7:S2405-4577(25)00309-2. doi: 10.1016/j.clnesp.2025.05.012. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, is a chronic inflammatory condition with global prevalence and varying incidence. The IBD pathogenesis involves intricate interactions among genetic, host and environmental factors, leading to dysregulated immune responses and chronic intestinal inflammation. Alongside elevated levels of inflammatory cytokines and altered miRNAs expression, more studies highlight significant dysbiosis in both fecal and ileal microbiota of IBD patients. This dysbiosis is characterized by an increase in pro-inflammatory and mucin- degrading bacteria (e.g., Fusobacterium spp., Escherichia spp.) and a decline in short-chain fatty acids (SCFAs) -producing microbes (e.g., Roseburia spp., Faecalibacterium spp.) which play a protective role in gut health. Diet emerges as a key environmental factor influencing IBD onset and progression and recent advancements in"omics" technologies, such as genomics, transcriptomics, and metabolomics, provide a deeper understanding of the molecular interactions between genes, gut microbiota (GM) and nutrition. Finally, new technologies like artificial intelligence (AI), further enhance findings by enabling data integration and personalized dietary strategies. In this scenario, this review aims to summarize accumulating data on the effects of dietary interventions in IBD patients and introduce the role of artificial intelligence (AI) in facilitating precision dietary approaches to improve IBD management.PMID:40345659 | DOI:10.1016/j.clnesp.2025.05.012

Physiol Behav. 2025 May 7:114944. doi: 10.1016/j.physbeh.2025.114944. Online ahead of print.ABSTRACTMethamphetamine (MA) use disorder has become a global public health problem, and the peripheral mechanisms underlying exercise as a potential treatment for MA addiction are still not fully understood. This study aims to identify a plasma metabolic biomarker in MA-administered mice under exercise interventions. The peripheral plasma metabolic profiles of C57BL/6J mice were quantified by ultra-high-performance liquid chromatography and tandem mass spectrometry metabolomics methods. The mice were randomized into saline control (C), MA model control (NE-MA) and MA model exercise intervention (E-MA) groups, and a conditioned place preference paradigm was used to assess drug reward. Anxiety-like behavior and cognitive behavior was evaluated using the open field and Y-maze tests. A total of 35 differential metabolites effectively distinguished between NE-MA and C groups. These metabolites are mainly involved in membrane lipid, energy, and amino acid metabolism. Compared with the NE-MA group, the expression of five reward-related metabolites in the E-MA group was reversed: L-tryptophan, niacinamide, uridine, 2'-deoxyuridine, and uric acid, which are involved in amino acid, energy, purine, and pyrimidine metabolism. Upregulation in uric acid and L-tryptophan levels was associated with improved anxiety-like behavior and cognitive function after exercise intervention. These metabolites may serve as markers of exercise intervention in MA addiction and deserve further study.PMID:40345472 | DOI:10.1016/j.physbeh.2025.114944

Mol Metab. 2025 May 7:102163. doi: 10.1016/j.molmet.2025.102163. Online ahead of print.ABSTRACTParkinson's disease (PD) is recognized as a systemic condition, with clinical features potentially modifiable by dietary intervention. Diets high in saturated fats and refined sugars significantly increase PD risk and exacerbate motor and non-motor symptoms, yet precise metabolic mechanisms are unclear. To investigate the interplay between diet and PD, we used a model of early-onset PD under chronic glycative stress induced by prolonged high-fat high-sucrose (HFHS) diet. We found this obesogenic diet drives loss of fat and muscle mass in early-onset PD mice, with a selective vulnerability of glycolytic myofibers. We show that PD mice and early-onset familial PD patients are under pervasive glycative stress with pathological accumulation of advanced glycation end products (AGEs), including two previously unknown glycerinyl-AGE markers.PMID:40345387 | DOI:10.1016/j.molmet.2025.102163

Mol Metab. 2025 May 7:102162. doi: 10.1016/j.molmet.2025.102162. Online ahead of print.ABSTRACTOBJECTIVE: Sucrose-rich diets promote hepatic de novo lipogenesis (DNL) and steatosis through interactions with the gut microbiota. However, the role of sugar-microbiota dynamics in the absence of dietary fat remains unclear. This study aimed to investigate the effects of a high-sucrose, zero-fat diet (ZFD) on hepatic steatosis and host metabolism in conventionally raised (CONVR) and germ-free (GF) mice.METHODS: CONVR and GF mice were fed a ZFD, and hepatic lipid accumulation, gene expression, and metabolite levels were analyzed. DNL activity was assessed by measuring malonyl-CoA levels, expression of key DNL enzymes, and activation of the transcription factor SREBP-1c. Metabolomic analyses of portal vein plasma identified microbiota-derived metabolites linked to hepatic steatosis. To further examine the role of SREBP-1c, its hepatic expression was knocked down using antisense oligonucleotides in CONVR ZFD-fed mice.RESULTS: The gut microbiota was essential for sucrose-induced DNL and hepatic steatosis. In CONVR ZFD-fed mice, hepatic fat accumulation increased alongside elevated expression of genes encoding DNL enzymes, higher malonyl-CoA levels, and upregulation of SREBP-1c. Regardless of microbiota status, ZFD induced fatty acid elongase and desaturase gene expression and increased hepatic monounsaturated fatty acids. Metabolomic analyses identified microbiota-derived metabolites associated with hepatic steatosis. SREBP-1c knockdown in CONVR ZFD-fed mice reduced hepatic steatosis and suppressed fatty acid synthase expression.CONCLUSION: Sucrose-microbiota interactions and SREBP-1c are required for DNL and hepatic steatosis in the absence of dietary fat. These findings provide new insights into the complex interplay between diet, gut microbiota, and metabolic regulation.PMID:40345386 | DOI:10.1016/j.molmet.2025.102162

Microb Pathog. 2025 May 7:107667. doi: 10.1016/j.micpath.2025.107667. Online ahead of print.ABSTRACTEnvironmental arsenic exposure and Helicobacter pylori (H. pylori) infection are widespread public health concerns, yet their combined effects on gastric pathophysiology remain poorly understood. This study investigated the impact of H. pylori infection and arsenic co-exposure on gastric barrier integrity, oxidative stress, and serum metabolic profiles using a murine model. Mice were divided into control, single-exposure (arsenic), and multiple exposure group (H. pylori infection and arsenic exposure). Gastric barrier function was assessed via immunofluorescence staining of ZO-1 and occludin proteins. Untargeted metabolomics, including PCA, PLS-DA, and KEGG pathway enrichment analyses, were employed to characterize serum metabolic alterations. Gene expression levels of IL-18, Nrf2, Keap1, Cat, Sod1, and Hmox1 in gastric tissues were quantified by qRT-PCR, with Spearman correlation analysis to evaluate metabolite-gene expression relationships. Fluorescence intensity of ZO-1 and occludin was significantly reduced in H. pylori-infected mice, with further deterioration under arsenic co-exposure. Metabolomic profiling revealed distinct serum metabolic perturbations across groups, with the multiple exposure group exhibiting more pronounced fluctuations in metabolite levels (e.g., lipids, amino acids, and peptides) and greater pathway diversity compared to single exposure groups. qRT-PCR analysis demonstrated synergistic upregulation of oxidative stress (Nrf2, Hmox1) and inflammatory (IL-18) markers in the multiple exposure group. Spearman correlation analysis identified significant associations between specific metabolites (e.g., acylcarnitines, bile acids) and antioxidant gene expression, suggesting bidirectional interactions between systemic metabolism and gastric oxidative responses. This study establishes a murine model of H. pylori infection and arsenic co-exposure, revealing synergistic disruption of gastric barrier function, oxidative homeostasis, and metabolic regulation. These findings provide critical insights into the pathophysiological interplay between microbial infection and environmental toxicants, highlighting potential therapeutic targets for mitigating combined exposure risks.PMID:40345345 | DOI:10.1016/j.micpath.2025.107667

Biochim Biophys Acta Rev Cancer. 2025 May 7:189343. doi: 10.1016/j.bbcan.2025.189343. Online ahead of print.ABSTRACTGliomas, the most prevalent primary brain tumors, continue to present significant challenges in oncology due to poor patient prognosis despite advances in treatment such as immunotherapy and cancer vaccines. Recent research highlights the potential of targeting tryptophan metabolism, particularly the kynurenine pathway (KP) and combinatorial approaches with immunotherapies, as a promising strategy in cancer research. The key enzymes of the kynurenine pathway, such as IDO1, IDO2, and TDO, and metabolites like kynurenine, kynurenic acid, and quinolinic acid, are implicated in fostering an immunosuppressive tumor microenvironment and promoting glioma cell survival. In glioblastoma, a highly aggressive glioma subtype, elevated IDO and TDO expression correlates with reduced survival rates. KP metabolites, such as kynurenine (KYN), 3-hydroxykynurenine (3-HK), kynurenic acid (KYNA), and quinolinic acid (QUIN), are involved in modulating immune responses, oxidative stress, neuroprotection, and neurotoxicity. This review synthesizes recent findings on the kynurenine pathway involvement in glioma pathogenesis, examining potential therapeutic targets within this pathway and discussing ongoing clinical trials that draw attention to treatments based on this pathway. Furthermore, it highlights novel findings on the post-translational modifications of kynurenine pathway enzymes and their regulatory roles, presenting their potential as therapeutic targets in gliomas.PMID:40345262 | DOI:10.1016/j.bbcan.2025.189343

J Sci Food Agric. 2025 May 9. doi: 10.1002/jsfa.14360. Online ahead of print.ABSTRACTBACKGROUND: This study aimed to investigate the anti-obesity mechanism of walnut-derived peptides (WMP) combined with intermittent fasting (IF) through modulating the gut microbiota-liver metabolism axis in high-fat-diet (HFD)-induced obese mice, providing theoretical support for dietary intervention strategies.METHODS: Fifty C57BL/6 mice were divided into five groups (n = 10): normal diet, HFD, WMP, IF and WMP + IF, with an 8-week intervention. Biochemical analysis, 16S rRNA sequencing, and untargeted liver metabolomics were employed to explore the underlying mechanisms.RESULTS: WMP + IF significantly alleviated hyperlipidemia, glucose metabolism disorders, insulin resistance, and visceral fat deposition in HFD mice, while suppressing systemic inflammation. Gut microbiota analysis revealed reduced abundance of Firmicutes, Kineothrix, and Dubosiella, along with a decreased Firmicutes/Bacteroidota (F/B) ratio, whereas Bacteroidota and CAG-873 were enriched. Correlation analysis demonstrated positive associations between Firmicutes and obesity-related markers (lipid profiles, liver dysfunction, pro-inflammatory cytokines), while Bacteroidota exhibited negative correlations. Untargeted metabolomics identified upregulated levels of 16-hydroxypalmitic acid and 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), alongside activation of ABC transporters and galactose metabolism pathways. Notably, 13(S)-HODE showed negative correlations with Firmicutes, F/B ratio, and Kineothrix, but positive correlations with Bacteroidota and CAG-873.CONCLUSION: The synergistic anti-obesity effects of WMP and IF are mediated through restoring gut microbial balance and reprogramming hepatic metabolic pathways. These findings highlight novel mechanisms involving the gut-liver axis, offering innovative strategies for obesity prevention through natural bioactive compounds combined with dietary interventions. © 2025 Society of Chemical Industry.PMID:40345144 | DOI:10.1002/jsfa.14360

Food Chem. 2025 Apr 30;486:144595. doi: 10.1016/j.foodchem.2025.144595. Online ahead of print.ABSTRACTCongou black tea, a traditional Chinese tea, shows regional variations in flavor and aroma. This study employed metabolomics techniques to compare Congou black tea from Zhejiang, Fujian, Sichuan, and Jiangxi. Using HS-SPME-GC-MS and SPME-GC-IMS, we identified 110 and 60 volatile organic compounds, respectively, with 5 common VOCs. Statistical analysis revealed 45 and 20 differential VOCs (VIP > 1, P < 0.05), essential for distinguishing the regions. The predominant compounds in FJ, SC, ZJ, and JX were esters, hydrocarbons, and ketones, respectively. UPLC-MS/MS analysis identified 180 non-volatile compounds, with SC showing a greater abundance of chemicals. KEGG pathway analysis revealed four common pathways and annotated 11 metabolites. These findings provide insights into the regional flavor differences in Congou black tea and highlight key factors influencing its quality.PMID:40345042 | DOI:10.1016/j.foodchem.2025.144595

Food Chem. 2025 May 6;486:144661. doi: 10.1016/j.foodchem.2025.144661. Online ahead of print.ABSTRACTMetabolomic analysis of volatile compounds in mead during aging in glass bottles and oak barrels revealed significant impacts on sensory characteristics. Using headspace solid-phase microextraction gas chromatography-mass spectrometry with three columns, 247 volatile compounds were identified, including 161 confirmed by standards. The XGBoost model accurately predicted sensory traits after 10 and 12 months of aging. Compared to freshly fermented mead, aged samples showed reduced off-flavors and increased herbal and fruity-sweet compounds, with OM samples exhibiting more pronounced changes (herbal compounds increased by 60.12 %, fruity-sweet compounds by 118.41 %, and off-flavors reduced by 17.07 %). PCA and OPLS-DA analyses highlighted the superiority of oak barrel aging. Key volatile compounds like ethyl caproate and ethyl heptanoate were identified through reconstitution and omission experiments. NetworkX analysis revealed rate-limiting steps in flavor compound formation, such as the conversion of benzaldehyde to phenylethanol and FPP to linalool. These findings provide key insights for optimizing mead's flavor. The abbreviations for all flavor compounds are provided in the supplementary file Table S1.PMID:40345026 | DOI:10.1016/j.foodchem.2025.144661

Aquat Toxicol. 2025 May 4;284:107395. doi: 10.1016/j.aquatox.2025.107395. Online ahead of print.ABSTRACTPerfluorodecanoic acid (PFDA), a long-chain perfluoroalkyl substance (PFAS), is known for its environmental persistence and potential toxicity. This study evaluated PFDA toxicity in the RTgill-W1 cell line, a model for aquatic toxicology, using a combination of cell viability assays, reactive oxygen species (ROS) measurements, and high-throughput metabolomics and lipidomics. PFDA exposure resulted in significant, dose-dependent reductions in cell viability and increased ROS production, with an EC₅₀ value of 51.9 ± 1.7 mg/L, highlighting its cytotoxic potential. Metabolomic profiling revealed dose-dependent disruptions in 168 metabolites, impacting pathways related to amino acid metabolism, carbohydrate metabolism, lipid metabolism, vitamin and cofactor metabolism, and nucleotide metabolism. Furthermore, lipidomic analysis identified 102 significantly altered lipids, primary affecting glycerolipid metabolism, fatty acid biosynthesis, glycerophospholipid metabolism, sphingolipid metabolism - suggesting compromised membrane integrity, energy production, and signalling processes. These findings underscore PFDA's capacity to interfere with critical cellular processes and highlight the utility of integrated omics approaches in elucidating the molecular mechanisms of PFAS toxicity. Future studies should focus on validating fish cell assays through short-term in vivo tests to enhance their reliability and ecological relevance.PMID:40344972 | DOI:10.1016/j.aquatox.2025.107395

J Pharm Biomed Anal. 2025 May 5;263:116948. doi: 10.1016/j.jpba.2025.116948. Online ahead of print.ABSTRACTScutellaria baicalensis Georgi (HQ) and Rubia cordifolia L. (QC) are clinically effective against ulcerative colitis (UC), but their synergistic mechanisms remain unclear. This study evaluated the therapeutic effects of HQ, QC, and their combination (HQ-QC) in dextran sulfate sodium (DSS)-induced colitis and explored underlying mechanisms. Mice were divided into normal, model, HQ, QC, HQ-QC, and 5-ASA groups. Colon tissue metabolomics was performed using UPLC-Q-TOF-MS, while network pharmacology and molecular docking identified potential anti-UC targets. The HQ-QC combination significantly alleviated weight loss, colon shortening, and histopathological damage, and improved intestinal barrier function and inflammation compared to single herbs. Metabolomics revealed xanthine, cytosine, and N-octanoylsphingosine-1-phosphate as key metabolites enriched in vascular smooth muscle contraction and fatty acid metabolism pathways. Network pharmacology identified 62 potential targets, with wogonin and xyloidone as major active compounds. KEGG analysis highlighted platelet activation as a key pathway, and molecular docking confirmed strong binding of wogonin and xyloidone to platelet activation-related targets including PIK3CG, NOS3, PTGS1, and MAPK14. These findings suggest HQ-QC exerts synergistic effects in treating DSS-induced UC by regulating vascular smooth muscle contraction and platelet activation, providing mechanistic insight into its clinical potential.PMID:40344969 | DOI:10.1016/j.jpba.2025.116948

Poult Sci. 2025 Apr 23;104(7):105205. doi: 10.1016/j.psj.2025.105205. Online ahead of print.ABSTRACTCoccidiosis, a protozoan disease caused by Eimeria parasites, significantly impacts the poultry industry. Traditional control methods involve the addition of anticoccidial drugs to feed, which has led to concerns over drug residues. Thus, the search for alternative treatments has become a research priority, with plant essential oils emerging as a promising option. In the study, we evaluated the anticoccidial effects of seven plant-derived products on Eimeria tenella using a broiler cage trial and calculated the anticoccidial index (ACI) to assess their efficacy. The results revealed that eucalyptus oil had the highest ACI (157.79), followed closely by eugenol (155.41), both nearing the 160.00 threshold. Eugenol demonstrated a lower oocyst output compared to eucalyptus oil, leading us to focus on the mechanism of eugenol's anticoccidial activity using transcriptomic and untargeted metabolomic analyses. Transcriptomic analysis of cecal tissue revealed 749 upregulated and 1057 downregulated differentially expressed genes (DEGs). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the extracellular matrix (ECM)-receptor interaction, cell adhesion molecules, and cytokine-cytokine receptor interaction, with the latter pathway showing significant expression differences in 40 genes. This suggests that eugenol modulates the immune response in broilers by regulating the expression of various cytokines. Metabolomic analysis identified 103 upregulated and 22 downregulated differential metabolites, with a high enrichment of the gut IgA production-related immune network pathway. Notably, vitamin A acid, a key metabolite in this pathway, was significantly upregulated. ELISA assays confirmed the upregulation of SIgA, a terminal product of this metabolic pathway. Additionally, several anti-inflammatory metabolites and prebiotics, such as fumaric acid, quinolinic acid, succinic acid, and d-raffinose, were significantly upregulated. These results indicate that eugenol modulates the intestinal immune network and levels of various anti-inflammatory metabolites and prebiotics, suggesting its role in anticoccidial activity through the regulation of DEGs and differential metabolites. This study demonstrates that eugenol has the potential to serve as a safe alternative or adjunct to anticoccidial drugs in poultry and deepens our understanding of its anticoccidial activity.PMID:40344707 | DOI:10.1016/j.psj.2025.105205

Poult Sci. 2025 May 1;104(7):105245. doi: 10.1016/j.psj.2025.105245. Online ahead of print.ABSTRACTIn the fierce market competition, high-quality chicken products often stand out. There are significant differences in meat quality between yellow and white feathered chickens. However, the underlying mechanisms that lead to the differences in their meat quality remain unclear. Single nucleotide polymorphisms (SNP) are effective molecular markers that can be utilized in marker-assisted breeding programs targeting chicken meat quality traits. Our research findings indicated that the bloodline of yellow-feathered chickens can significantly alter the meat quality traits of chickens, especially in terms of the shear force and meat color of the breast muscle. Additionally, through metabolomic, lipidomic, and RNA-seq, we identified differentially expressed metabolites, lipids, and genes that influence meat quality. Furthermore, we discovered a key gene, the purinergic receptor P2 × 5 (P2RX5), which significantly contributes to meat quality traits. We identified five SNP sites within the P2RX5 gene and conducted genotyping. Three of these SNP sites were found to be significantly associated with meat quality traits in chickens, such as the a*value and cooking loss. These results indicated that our findings provide potential molecular markers for changing meat quality traits in chickens. However, due to our small sample size and the absence of testing on males, the generalizability of the results may be insufficient.PMID:40344706 | DOI:10.1016/j.psj.2025.105245

Biomed Pharmacother. 2025 May 7;187:118146. doi: 10.1016/j.biopha.2025.118146. Online ahead of print.ABSTRACTGenetic PLA2G6 variants are associated with C-reactive protein in humans. Myeloid-specific PLA2G6-deficient (Pla2g6M-/-) mice show increased hepatic myeloperoxidase and recruitment of granulocytes in response to lipopolysaccharide (LPS). We hypothesized that Pla2g6M-/- mice could be protected from acetaminophen (APAP) hepatotoxicity whereby neutrophils, eosinophils, and alternatively activated macrophages are reportedly protective. Herein, Pla2g6M-/- mice treated with 300 mg/kg APAP for 24 h showed attenuated hepatic necrosis and plasma cytokines, and with elevated levels of Ly6Clo in peripheral blood mononuclear cells and plasma lipoxin A4. Remarkably, bone-marrow-derived macrophages (BMDMs) from untreated Pla2g6M-/- mice exhibited elevated baseline expression of cPLA2α, NOX2, Rac1, Arg-1, phospho-MLKL, and iNOS protein, which was exacerbated by LPS in vitro. APAP administration preconditioned Pla2g6M-/- BMDMs for further activation of enzymes involving in phagocytosis (Rac1 and phospho-MLKL) and eicosanoids (COX2 and A15LOXB). Pla2g6M-/- BMDMs showed an increased release of pro-resolution lipid mediators lipoxin A4, PGE2, and 15d-PGJ2, which was further elevated by LPS in vitro or APAP in vivo. Phagocytic gene signatures (myeloperoxidase and NOX2) were also upregulated in livers of untreated and APAP-treated Pla2g6M-/- mice. APAP protection in Pla2g6M-/- mice was associated with increased proportion of neutrophils (Ly6G), eosinophils (eosinophilic cationic protein), and M2 macrophages (CD206) in/at the portal tract and central vein as determined by immunohistochemistry. Thus, myeloid-specific PLA2G6 deficiency preconditioned macrophages for eicosanoid and phagocytic pathways rendering protection against APAP hepatotoxicity. Our results may be applicable to patients with PLA2G6 mutations, and PLA2G6 inhibition specifically in myeloid cells may represent a new strategy to alleviate APAP poisoning.PMID:40344700 | DOI:10.1016/j.biopha.2025.118146

ACS Chem Biol. 2025 May 9. doi: 10.1021/acschembio.4c00562. Online ahead of print.ABSTRACTThe fungus Aspergillus fumigatus and the bacterium Burkholderia cenocepacia cause fatal respiratory infections in immunocompromised humans and patients with lung disease, such as cystic fibrosis (CF). In dual infections, antagonistic interactions contribute to increased mortality. These interactions are further altered by the presence of antimicrobial and antifungal agents. However, studies performed to date on chemical interactions between clinical B. cenocepacia and A. fumigatus have focused on pathogens in isolation and do not include the most abundant chemical signal, i.e., clinically administered therapeutics, present in the lung. Here, we characterize small molecule-mediated interactions between B. cenocepacia and A. fumigatus and their shift in response to trimethoprim exposure by using metabolomics and mass spectrometry imaging. Using these methods, we report that the production of several small-molecule natural products of both the bacteria and the fungus is affected by cocultivation and exposure to trimethoprim. By systematic analysis of metabolomics data, we hypothesize that the B. cenocepacia-encoded ham gene cluster plays a role in the trimethoprim-mediated alteration of bacterial-fungal interactions. We support our findings by generating a genetically modified strain lacking the ham gene cluster and querying its interaction with A. fumigatus. Using comparative analyses of the extracts of wild-type and knockout strains, we report the inactivation of a bacterially produced antifungal compound, fragin, by A. fumigatus, which was verified by the addition of purified fragin to the A. fumigatus culture. Furthermore, we report that trimethoprim does not inhibit fungal growth, but affects the biochemical pathway for DHN-melanin biosynthesis, an important antifungal drug target, altering the pigmentation of the fungal conidia and is associated with modification of ergosterol to ergosteryl-3β-O-l-valine in coculture. This study demonstrates the impact of therapeutics on shaping microbial and fungal metabolomes, which influence interkingdom interactions and the expression of virulence factors. Our findings enhance the understanding of the complexity of chemical interactions between therapeutic compounds, bacteria, and fungi and may contribute to the development of selective treatments.PMID:40344688 | DOI:10.1021/acschembio.4c00562

Plant J. 2025 May;122(3):e70209. doi: 10.1111/tpj.70209.ABSTRACTAllene oxide cyclase (AOC) catalyzes the formation of 12-oxo-phytodienoic acid (12-OPDA) and represents an understudied step in jasmonate biosynthesis. Here the effects of eliminating AOC function in maize (Zea mays) are investigated. Gene editing was used to disrupt a pair of redundant AOC-coding genes, and mutants were analyzed with targeted metabolomics in a biochemical characterization of jasmonate deficiency. Our findings confirm essential roles for AOC in male flower development and resistance to biotic stresses. Metabolomic examinations show that AOC deficiency leads to a 90% reduction in 12-OPDA and a 99% reduction in jasmonic acid (JA) and JA-Isoleucine after treatment with fall armyworm. The presence of 12-OPDA in equal proportions of cis-(+) and cis-(-) stereochemical isomers indicates nonenzymatic allene oxide cyclization in the absence of functional AOC. This residual 12-OPDA is not converted into JA or other downstream jasmonates during herbivory, revealing the necessity of enzymatic cyclization of allene oxide by AOC for insect-induced JA and JA-dependent defense responses. The AOC-deficient mutants developed here provide a new tool for investigating the roles of jasmonates in maize.PMID:40344686 | DOI:10.1111/tpj.70209

PLoS One. 2025 May 9;20(5):e0322853. doi: 10.1371/journal.pone.0322853. eCollection 2025.ABSTRACTOxidative stress is a major cause of semen quality decline in old roosters. Dendrobium nobile Lindl (DNL), a Chinese herbal medicine, exhibits excellent antioxidant activity. Therefore, the present study aimed to investigate the effects of dietary DNL supplementation on semen quality, antioxidant capacity, reproductive hormone levels, and testicular tissue structure in aged roosters. This study further aimed to elucidate the potential mechanism for improving reproductive performance. Thus, the expression of antioxidant defense system-related genes was verified, and metabolomic analysis was performed. Twenty 56-week-old recessive, white-feathered roosters were randomly assigned into two groups. The DNL group was fed a basal diet supplemented with 2500 mg/kg DNL for 60 days, whereas the control group was fed a basal diet. Here, DNL improved the semen quality (sperm density and motility) and antioxidant capacity of aged roosters, increased the expression of genes in the Nrf2 pathway, increased serum hormone levels, and delayed testicular tissue degradation. Seventy-six differential metabolites that are mainly enriched in amino acid biosynthesis pathways, taurine and hypotaurine metabolism, and cysteine and methionine metabolism were identified. DL-serine, DL-cysteine, and α-ketoglutarate were related to improved testicular antioxidant capacity. In this study, dietary supplementation with 2500 mg/kg DNL delayed the decline in reproductive performance by improving the antioxidant capacity of aging roosters. These findings could facilitate the use of DNL as a feed additive to improve the reproductive performance of aged roosters.PMID:40344569 | DOI:10.1371/journal.pone.0322853

Hepatology. 2025 May 9. doi: 10.1097/HEP.0000000000001394. Online ahead of print.ABSTRACTBACKGROUND AIMS: Research on metabolic reprogramming in hepatocellular carcinoma (HCC) has increased; however, studies on the metabolism of glycerolipids or interactions between different pathways remain scarce. Enzymes of glycerol phosphate dehydrogenase (GPD) family, which regulate glycerol-3-phosphate shuttle, link the metabolic processes of glycolysis and glycerolipids. Therefore, we aimed to understand the role and regulation of GPDs in HCC.APPROACH RESULTS: We performed transcriptomic analysis on clinical HCC samples from in-house and public cohorts and detected upregulation of glycerol-3-phosphate dehydrogenase 1 like (GPD1L) among GPD family genes in HCC. Further analysis showed that high GPD1L expression was associated with more frequent venous invasion and shorter overall survival. Consistent with these clinical findings, GPD1L knockdown suppressed invasiveness of HCC cells, reduced colony- and sphere-forming abilities, and inhibited stemness gene expression in vitro, while also inhibiting tumor growth and metastasis in vivo. On the other hand, we used mass-spectrometry-based metabolomics to confirm that GPD1L facilitated the biogenesis of the glycerolipid precursor glycerol-3-phosphate (G3P) from dihydroxyacetone phosphate (DHAP). Further untargeted lipidomic analysis revealed that GPD1L supported triacylglycerol synthesis. Additionally, our study identified E74 like E-Twenty-Six transcription factor 1 (ELF1) as a direct activator of GPD1L transcription, binding to the GPD1L promoter to boost its transcription while reducing GPD1L expression when ELF1 levels were lowered.CONCLUSIONS: GPD1L is overexpressed in human HCCs and associated with worse clinical outcomes. Aberrant GPD1L expression, driven by ELF1, facilitates conversion of DHAP to G3P conversion to support triacylglycerol synthesis in HCC, promoting tumor growth and metastasis.PMID:40344414 | DOI:10.1097/HEP.0000000000001394