PubMed

Mol Metab. 2025 Apr 1:102132. doi: 10.1016/j.molmet.2025.102132. Online ahead of print.ABSTRACTOBJECTIVE: Liver fibrosis is a crucial condition for evaluating the prognosis of chronic liver disease. Lectin-1ike oxidized low density lipoprotein receptor-1 (LOX-1) has been shown potential research value and therapeutic targeting possibilities in different fibrotic diseases. However, the role of LOX-1 and the underlying mechanisms in liver fibrosis progression remain unclear.METHODS: LOX-1 expression was detected in liver tissues from patients and rodents with liver fibrosis. LOX-1 knockout rats were subjected to CCl4 or methionine and choline-deficient diet (MCD) to induce liver fibrosis. Transcriptomic and metabolomics analysis were used to investigate the involvement and mechanism of LOX-1 on liver fibrosis.RESULTS: We found that LOX-1 exacerbated liver fibrosis by promoting hepatic stellate cells (HSCs) activation. LOX-1 deletion reversed the development of liver fibrosis. We further verified that LOX-1 drove liver fibrosis by reprogramming glutamine metabolism through mediating isoform switching of glutaminase (GLS). Mechanistically, we revealed the crucial role of the LOX-1/OCT1/GLS1 axis in the pathogenesis of liver fibrosis. Moreover, LOX-1 rewired ammonia metabolism by regulating glutamine metabolism-urea cycle to drive the progression of liver fibrosis.CONCLUSIONS: Our findings uncover the pivotal role of LOX-1 in the progression of liver fibrosis, enrich the pathological significance of LOX-1 regulation of hepatic ammonia metabolism, and provide an insight into promising targets for the therapeutic strategy of liver fibrosis, demonstrating the potential clinical value of targeting LOX-1 in antifibrotic therapy.PMID:40180177 | DOI:10.1016/j.molmet.2025.102132

Toxicology. 2025 Apr 1:154131. doi: 10.1016/j.tox.2025.154131. Online ahead of print.ABSTRACTCopper oxide nanoparticles (CuO NPs) are increasingly used in various industrial fields, and the toxicity of CuO NPs raises concerns. However, the CuO NPs-induced pulmonary inflammation and the underlying mechanism have not been fully illustrated. Cellular cuproptosis provides a new perspective to elucidate the toxicity of CuO NPs. Here, we exposed C57BL/6 mice and murine alveolar macrophage cells (MH-S) to CuO NPs, respectively. A suspension of 2mg/mL CuO NPs was directly once administered by intratracheal instillation, and mice were sacrificed on day 7. The histopathology results showed that CuO NPs induced pulmonary inflammation in C57BL/6 mice. CuO NPs increased Cu2+ levels by 203.0% in mouse lung tissues. Also, CuO NPs increased the cuproptosis-related indicators of ferredoxin (FDX1), dihydrolipoamide succinyltransferase (DLST), dihydrolipoamide acetyltransferase (DLAT) and Cu transporter 1 (CTR1) in both mouse lung tissues and MH-S cells. Transcript sequencing and non-targeted metabolomics indicated that CuO NPs induced cellular cuproptosis and inflammatory responses both in vivo and in vitro. Interleukin-17a (IL-17A) was remarkably increased in the process of CuO NPs-induced cellular cuproptosis. Additionally, interference of FDX1 reduced cellular cuproptosis and decreased the release of IL-17A. In summary, CuO NPs increased the accumulation of intracellular Cu2+ and the expressions of cuproptosis-related proteins, induced FDX1-mediated cuproptosis, and led to pulmonary inflammation in mice. This study highlights the respiratory toxicity of CuO NPs and reveals a unique cuproptosis-driven mechanism underlying the CuO NPs-induced pulmonary inflammation.PMID:40180017 | DOI:10.1016/j.tox.2025.154131

Neuroimmunomodulation. 2025 Apr 3:1-15. doi: 10.1159/000545484. Online ahead of print.ABSTRACTThe gut microbiota is increasingly recognized as a critical regulator of brain function, influencing neurodevelopment, adult brain physiology, and disease vulnerability in part through its interactions with microglia, the resident immune cells of the central nervous system. Emerging evidence demonstrates that microbial metabolites, beginning prenatally and persisting throughout the lifespan, regulate fundamental aspects of microglial biology including maturation, metabolic function, and activation. Microglia from germ-free mice exhibit persistent immaturity, altered energy metabolism, and blunted inflammatory responses, which are partially reversible by restoring microbial communities or supplementing key microbial metabolites. Short-chain fatty acids, tryptophan-derived indoles, and other bacterial metabolites derived from the gut microbiota shape microglial function to modulate neurons and synaptic architecture, and influence neuroinflammatory processes. These findings reveal distinct metabolite-driven pathways linking microbial composition to microglial phenotypes, positioning the microbiome as a potential key influencer of neurodevelopmental trajectories and the pathophysiology of psychiatric and neurological disorders. Despite recent advances, major knowledge gaps persist in understanding the precise molecular intermediaries and mechanisms through which metabolite signaling to microglia shape neural function to influence susceptibility or resilience to brain-based disorders. Understanding both the bacterial metabolomic landscape and its collective impact on microglial programming holds substantial therapeutic promise, offering avenues to target microbial metabolite production or administer them directly to modulate brain health.PMID:40179831 | DOI:10.1159/000545484

J Hazard Mater. 2025 Mar 29;492:138088. doi: 10.1016/j.jhazmat.2025.138088. Online ahead of print.ABSTRACTRecent findings indicate elevated levels of total Hg in the waters of the Lagoa Mundaú-Manguaba Estuarine Complex (CELMM, Maceió-AL, Brazil) and the biological fluids of fishermen that live near CELMM. This study assessed Hg levels in whole blood and the functionality, structure, morphology, and oxidative stress of blood cells from fishermen (n = 60) compared with control volunteers (n = 65). A systematic assessment was performed, and our results revealed increased Hg concentration in fishermen's blood. Erythrocyte functionality showed a 39 % decrease in O2 uptake. For peripheral blood mononuclear cells (PBMCs), ROS generation demonstrated an 87 and 116 % increase in O2•- and H2O2 production, respectively, confirmed by fluorescence microscopy. Scanning electron microscopy showed increased roughness in the PBMCs membrane. Secondary oxidative stress markers revealed a reduction in the GSH/GSSG ratio and thiol content. MDA production increased by 89 %, while antioxidant enzyme activities showed a 159 and 22 % increase in SOD and CAT, respectively; otherwise, a depletion of 33 % in GPx. The metabolomic profile exhibited changes in essential amino acids for GSH formation, and energy pathways were modified. Finally, our data indicates that exposure to a polluted environment alters redox status, leading to compromised function and structure of blood cells.PMID:40179776 | DOI:10.1016/j.jhazmat.2025.138088

J Am Soc Mass Spectrom. 2025 Apr 3. doi: 10.1021/jasms.4c00467. Online ahead of print.ABSTRACTTargeted quantification metabolomics provides dynamic insights across various domains within the life sciences. Nevertheless, maintaining high-quality data obtained through liquid chromatography-mass spectrometry presents ongoing challenges. It is essential to develop normalization methods to correct for unwanted variations in metabolomic profiling such as batch effects and analytical drift. In this study, we assessed the normalization efficacy of Norm ISWSVR in targeted quantification metabolomics by comparing it with IS normalization and SERRF normalization. Consequently, Norm ISWSVR demonstrated exceptional efficacy in mitigating batch effects and reducing the relative standard deviation of quality control samples, in addition to correcting signal drift. Following normalization with Norm ISWSVR, the number of metabolites suitable for quantification increased with high precision. Collectively, Norm ISWSVR proves to be a robust and reliable method for enhancing data quality in targeted metabolomics, establishing itself as a promising approach for metabolomics research.PMID:40179246 | DOI:10.1021/jasms.4c00467

PLoS Comput Biol. 2025 Apr 3;21(4):e1012901. doi: 10.1371/journal.pcbi.1012901. eCollection 2025 Apr.ABSTRACTThe Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large language model (LLM). Completed workflows are compatible with Common Workflow Language (CWL) and can be published as research publications, slideshows, and posters. To demonstrate how the PWB generates meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases prioritizes drug targets for individual cancer patients using data from the NIH Common Fund programs GTEx, LINCS, Metabolomics, GlyGen, and ExRNA. The workflows created with PWB can be repurposed to tackle similar use cases using different inputs. The PWB platform is available from: https://playbook-workflow-builder.cloud/.PMID:40179105 | DOI:10.1371/journal.pcbi.1012901

Cancer Epidemiol Biomarkers Prev. 2025 Apr 3. doi: 10.1158/1055-9965.EPI-24-1646. Online ahead of print.ABSTRACTBACKGROUND: The metabolomics approach using blood samples from epidemiological studies has the potential to elucidate pathways or uncover biomarkers for breast cancer (BC) outcomes. Therefore, understanding the within-person reproducibility of the blood metabolome and the factors that influence metabolite levels over time in BC survivors are crucial, but these remain largely unknown.METHODS: We estimated the within-person reproducibility of plasma metabolites in 61 Black BC survivors from the Women's Circle of Health Follow-Up Study. Samples were collected from each participant at two time points, approximately two and three years post-diagnosis. Untargeted metabolomic profiles were analyzed by Metabolon using ultrahigh-performance liquid chromatography-tandem mass spectrometry. We calculated the intraclass correlation coefficients (ICC) for each metabolite by dividing the between-person variance by the total variance. ICCs were compared across preanalytical factors (e.g., fasting) and participant characteristics using the Wilcoxon test.RESULTS: Among 857 named metabolites, the median ICC was 0.58 (interquartile range [IQR]: 0.44-0.70). 16.6% of the metabolites showed high within-person reproducibility (ICC≥0.75), spanning all metabolite classes, while 65.6% had an ICC within 0.4-0.75, and 17.9% had an ICC<0.4. Reasonable ICCs were also observed for non-fasting samples (median 0.53, IQR: 0.39-0.67), although lower than those for fasting samples (median 0.63, IQR: 0.45-0.77). ICCs were slightly lower in younger, non-obese participants and in women with estrogen receptor-positive BC.CONCLUSIONS: The within-person reproducibility of plasma metabolites over 1 year among BC survivors was generally acceptable.IMPACT: A single-time-point measurement could be useful in evaluating associations between metabolites and breast cancer outcomes.PMID:40178939 | DOI:10.1158/1055-9965.EPI-24-1646

J Agric Food Chem. 2025 Apr 3. doi: 10.1021/acs.jafc.4c12906. Online ahead of print.ABSTRACTThe exopolysaccharides (EPSs) from Agaricus bitorquis (Quél.) Sacc. Chaidam (ABSC) have great application value due to their significant biological activities. In order to promote ABSC growth and increase EPS production, the method of adding antioxidants and its regulatory mechanism were studied. Taking the anthocyanin extract from Lycium ruthenicum Murr (ALR) as the best regulatory factor, the optimal dosage was determined to be 0.06 mg/mL, and the EPS yield was significantly increased by 65.46% (p < 0.05) compared with the control group (at the peak). Through the combined analysis of metabolomics and transcriptomics, the results showed that ALR promoted mycelial growth and enhanced EPS synthesis and release by upregulating the biosynthesis pathway of amino acids and UDP-monosaccharides, the degradation pathway of toxic and harmful substances in cells, and the desaturation metabolic pathway of fatty acids. At the same time, it was found that the various regulatory effects of ALR on EPS synthesis were related to the synergistic effects of its main active ingredients. These results not only provide a new strategy for the efficient production of EPS but also lay a solid scientific foundation for future research applications.PMID:40178384 | DOI:10.1021/acs.jafc.4c12906

Anal Chem. 2025 Apr 3. doi: 10.1021/acs.analchem.4c05315. Online ahead of print.ABSTRACTMetabolomics, which involves the comprehensive analysis of small molecules within biological systems, plays a crucial role in elucidating the biochemical underpinnings of physiological processes and disease conditions. However, current coverage of the metabolome remains limited. In this study, we present a heuristic strategy for untargeted metabolomics analysis (HeuSMA) based on multiple chromatographic gradients to enhance the metabolome coverage in untargeted metabolomics. This strategy involves performing LC-MS analysis under multiple gradient conditions on a given sample (e.g., a pooled sample or a quality control sample) to obtain a comprehensive metabolomics data set, followed by constructing a heuristic peak list using a retention index system. Guided by this list, heuristic peak picking in quantitative metabolomics data is achieved. The benchmarking and validation results demonstrate that HeuSMA outperforms existing tools (such as MS-DIAL and MZmine) in terms of metabolite coverage and peak identification accuracy. Additionally, HeuSMA improves the accessibility of MS/MS data, thereby facilitating the metabolite annotation. The effectiveness of the HeuSMA strategy was further demonstrated through its application in serum metabolomics analysis of human hepatocellular carcinoma (HCC). To facilitate the adoption of the HeuSMA strategy, we also developed two user-friendly graphical interface software solutions (HPLG and HP), which automate the analysis process, enabling researchers to efficiently manage data and derive meaningful conclusions (https://github.com/Lacterd/HeuSMA).PMID:40178068 | DOI:10.1021/acs.analchem.4c05315

Int J Cancer. 2025 Apr 3. doi: 10.1002/ijc.35427. Online ahead of print.ABSTRACTIncreasing evidence links the gut microbiome to carcinogenesis. Disruptions in estrogen regulation by the estrobolome-gut microbiota with estrogen-related functions-may promote breast cancer. However, precise information on estrobolome targets and their underlying mechanisms is limited. This review identifies relevant targets for measuring the estrobolome, focusing on enzymes and microbial taxa involved in processing estrogens, precursors, metabolites, and phytoestrogens, to facilitate the exploration of potential links to breast cancer. Evidence from breast cancer case-control studies is synthesized to assess alignment with these targets, highlight gaps in the evidence, and suggest new paths forward. Findings from case-control studies were heterogeneous and showed limited alignment with estrobolome targets, with only Escherichia coli and Roseburia inulinivorans identified as differentially abundant and functionally relevant between cases and controls. The lack of compelling evidence for estrobolome-specific mechanisms may reflect measurement challenges or may suggest that broader ecological changes in the microbiome, which influence a network of interacting mechanisms, are more influential for carcinogenesis. To clarify the estrobolome's role in breast cancer, future research should use advanced sequencing techniques and methods such as metabolomics and transcriptomics, while considering clinical and behavioral factors that may modify estrobolome mechanisms.PMID:40177842 | DOI:10.1002/ijc.35427

Acta Pharm Sin B. 2025 Feb;15(2):973-990. doi: 10.1016/j.apsb.2024.10.011. Epub 2024 Oct 30.ABSTRACTIncreasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.PMID:40177576 | PMC:PMC11959932 | DOI:10.1016/j.apsb.2024.10.011

ISME Commun. 2025 Feb 13;5(1):ycaf030. doi: 10.1093/ismeco/ycaf030. eCollection 2025 Jan.ABSTRACTMicrobial methane-consuming communities significantly impact biogeochemical processes and greenhouse gas emissions. In this study, we explored secondary metabolites produced by methane-oxidizing bacteria (MOB) and their ecological roles. We analyzed the volatile profiles of four MOB strains under controlled conditions and conducted a meta-analysis using high-quality genomes from 62 cultured MOB strains and 289 metagenome-assembled genomes to investigate their potential for producing secondary metabolites. Results show species-specific volatile production, such as germacrene by Methylobacter luteus, which may play a role in the regulation of environmental methane consumption. The meta-analysis revealed that biosynthetic gene clusters (BGCs) for terpenes and β-lactones were more prevalent in the Methylocystaceae and/or Beijerinckiaceae families, while aryl polyene BGCs were dominant in the Methylococcaceae family, reflecting habitat-specific adaptations. These findings advance our understanding of the metabolic capabilities of MOB and underscore the importance of integrating experimental data with genomic and metabolomic analyses to elucidate their ecology, environmental interactions, and contributions to methane cycling.PMID:40177465 | PMC:PMC11964084 | DOI:10.1093/ismeco/ycaf030

Front Plant Sci. 2025 Mar 19;16:1502436. doi: 10.3389/fpls.2025.1502436. eCollection 2025.ABSTRACTINTRODUCTION: In Mediterranean areas like Spain, global warming has endangered stone fruit production by reducing chill accumulation, leading to significant agronomical and economical losses. To mitigate this issue, agrochemicals have been applied for decades to promote endodormancy release and initiate flowering. However, many of these chemicals have been associated with strong phytotoxicity, resulting in their recent ban. As a result, identifying novel pathways to modulate endodormancy release is critical and essential for developing effective, non-toxic agrobiochemicals.METHODS: In this study, we investigated the effect of two different agrochemicals mixes: 1% Broston® + 5% NitroActive® and 3% Erger® + 5% Activ Erger®, sprayed on peach trees during endodormancy over two years, followed by non-target metabolomic analyses on flower buds to identify metabolic changes in treated versus control trees.RESULTS AND DISCUSSION: Significant variations were observed in metabolites from the abscisic acid and phenylpropanoid pathways. Notably, six types of phospholipids were identified, with most increasing exclusively in treated samples during endodormancy release. These results were in concomitance with the increased expression of 4-coumarate-CoA ligase 1, 9-cis-epoxycarotenoid dioxygenase, and xanthoxin dehydrogenase genes. In a subsequent validation experiment performed in the third year, branches treated with phospholipids and cinnamic, caffeic, and abscisic acids advanced endodormancy release by one to two weeks, which represents the first evidence of endodormancy release modulation by the use of these metabolites. Moreover, this study contributes to our understanding of the biochemical mechanisms involved in endodormancy release and highlights the potential of phenylpropanoids, phospholipids, and related compounds as targets for developing sustainable agrochemicals, addressing challenges posed by climate change to Prunus spp. cultivation.PMID:40177021 | PMC:PMC11962625 | DOI:10.3389/fpls.2025.1502436

Front Plant Sci. 2025 Mar 19;16:1549156. doi: 10.3389/fpls.2025.1549156. eCollection 2025.ABSTRACTPlant chloroplasts produce excess reactive oxygen species (ROS) during photosynthesis, particularly under biotic and abiotic stress conditions. These adverse environmental stresses lead to significant alterations in various cellular components, especially within the chloroplast, which serves as a key stress-sensor organelle. The stress response of chloroplasts can trigger plastid-to-nucleus retrograde signaling and enhance the biosynthesis of biologically active compounds and phytohormones, which are mechanisms that aid plants in acclimating to environmental stress. While ROS act as signaling molecules to help re-adjust cellular metabolic homeostasis, they also risk damaging chloroplasts' structural and functional integrity. Recent research on stress-induced plant metabolism has provided new insights into the chloroplast's stress response. In particular, advancements in mass spectrometry (MS) techniques have expanded our understanding of how oxidative stress affects plants through metabolomics analyses of metabolites involved in this process. Here, we emphasize the MS-based profiling of lipids, apocarotenoids, and phytohormones linked to ROS-triggered processes in plants. Moreover, we discuss the plants' metabolic responses to abiotic stress. Finally, we outline future directions for chloroplast stress research. We advocate for integrating MS-based metabolomics with biochemical and molecular genetic approaches to discover new signaling molecules and identify interconnected signaling components that function across multiple chloroplast signaling pathways.PMID:40177010 | PMC:PMC11962030 | DOI:10.3389/fpls.2025.1549156

Front Pharmacol. 2025 Mar 19;16:1565030. doi: 10.3389/fphar.2025.1565030. eCollection 2025.ABSTRACTINTRODUCTION: Obesity, a global health challenge, is characterized by excessive fat accumulation and associated metabolic disorders. The ZhiZhu decoction, a traditional Chinese herbal formula consisting of Citrus aurantium L. (ZS, ZhiShi in Chinese) and Atractylodes macrocephala Koidz (BZ, Baizhu in Chinese), is widely recognized in clinics for its gastrointestinal regulatory effects.METHODS: The chemical composition of ZS-BZ essential oil (ZBEO) was characterized using gas chromatography-mass spectrometry (GC-MS). Concurrently, we conducted in vitro investigations using HepG2 hepatoma cells to evaluate its anti-lipid deposition potential. To further elucidate the anti-obesity mechanisms, an in vivo model was established through high-fat diet (HFD)-induced obese rats, followed by transdermal ZBEO administration. Systemic analyses were performed integrating serum metabolomic profiling via UPLC-QTOF-MS and gut microbiota dynamics assessment through 16S rRNA gene sequencing.RESULTS: ZBEO, rich in atractylon, D-limonene, and γ-elemene and shown to reduce lipid accumulation. Transdermal ZBEO administration in obese rats led to significant weight loss and improved serum metabolic indexes related to the POMC/CART signaling pathway. Additionally, ZBEO altered gut microbiota, enhancing beneficial bacteria and affecting metabolic pathways linked to obesity.DISCUSSION: We discovered that ZBEO exerts a significant influence on obesity by modulating key biological processes, including glucose metabolism, lipid metabolism, and the composition of gut microbiota.PMID:40176906 | PMC:PMC11962428 | DOI:10.3389/fphar.2025.1565030

Front Immunol. 2025 Mar 19;16:1557790. doi: 10.3389/fimmu.2025.1557790. eCollection 2025.ABSTRACTINTRODUCTION: Lung cancer is characterized by a poor prognosis and is a significant comorbidity of chronic obstructive pulmonary disease (COPD). Therefore, effective chemopreventive agents are warranted. We evaluated the effects of the cyclooxygenase-2 (COX-2) inhibitor celecoxib on the prevention of lung-carcinoma development using an intermittent smoking-induced lung-carcinoma mouse model. Additionally, we explored COX-2's role in lipid metabolism.METHODS: Male A/J mice were exposed to sham air or mainstream cigarette smoke for 20 weeks. Vehicle or celecoxib was administered via intragastric feeding once daily. Lung tissues were analyzed for tumor nodules and emphysema; the bronchoalveolar lavage fluid was collected for cell counting. COX-2 expression was measured using real-time polymerase chain reaction and western blotting; lipidomic analysis was conducted using liquid chromatography-tandem mass spectrometry. Cell proliferation and colony-forming assays were performed on LA-4 cells to assess the effects of prostaglandins and COX-2 inhibitors.RESULTS: Intermittent smoking exposure increased lung adenomas, adenocarcinomas, and COX-2 expression. Lung adenomas were characterized by abundant COX-2-positive cells. Celecoxib reduced intermittent smoking-induced inflammation, emphysema, and cell counts in the bronchoalveolar lavage fluid and decreased the incidence of lung adenocarcinomas, whereas the total number of observed lung tumors was unchanged. Celecoxib markedly suppressed single-smoke-induced prostaglandin E2 (PGE2) production in the airway. PGE2 increased LA-4 cell viability via the EP4 receptor and promoted colony formation.DISCUSSION: Celecoxib effectively inhibited lung-carcinoma development, inflammation, and emphysema, demonstrating the potential for chemoprevention in smokers and patients with COPD. Further studies on EP4 inhibitors for the prevention of emphysema and lung cancer are warranted.PMID:40176805 | PMC:PMC11961424 | DOI:10.3389/fimmu.2025.1557790

Anal Chem. 2025 Apr 3. doi: 10.1021/acs.analchem.4c06345. Online ahead of print.ABSTRACTCompound 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA) is an emerging per- and polyfluoroalkyl substance (PFAS) with potential toxicity and health risks to biosystems and ecosystems. Here, we developed a metabolomics method based on single-cell mass spectrometry to investigate the hepatotoxicity and heterogeneous responses in zebrafish exposed to 6:2 Cl-PFESA. Zebrafish were exposed to an environmentally relevant concentration (200 ng/L) of 6:2 Cl-PFESA for 14 days. The livers were dissociated and prepared as cell suspensions and then introduced to high-throughput single-cell mass spectrometry for analysis of 6:2 Cl-PFESA and endogenous metabolites in individual primary liver cells. Significant sex-specific heterogeneity in 6:2 Cl-PFESA accumulation was observed (p < 0.05). Metabolomics analysis revealed perturbations in lipid metabolism, particularly affecting unsaturated fatty acids, ether lipids, and sphingolipids in zebrafish liver cells, indicating potential hepatotoxicity. Sex-dependent metabolic responses were evident: males showed notable changes in glucose and fatty acid metabolism, whereas females experienced pronounced disruptions in glycerophospholipid and amino acid pathways. ROC analysis identified sex-specific biomarkers, including FA(18:3) and FA(16:1) in males (AUC > 0.85), as well as proline and phosphatidylcholine in females (AUC > 0.90). These findings reflect metabolic dysregulation and highlight sex-specific responses. This study demonstrates the feasibility of single-cell metabolomics to elucidate the cellular mechanisms and metabolic responses of pollutant exposure, offering insights into precise and comprehensive toxicity assessments at the single-cell level.PMID:40176633 | DOI:10.1021/acs.analchem.4c06345

Gut Microbes. 2025 Dec;17(1):2483783. doi: 10.1080/19490976.2025.2483783. Epub 2025 Apr 2.ABSTRACTUrbanization has significantly transformed dietary habits worldwide, contributing to a globally increased burden of non-communicable diseases and altered gut microbiota landscape. However, it is often overlooked that the adverse effects of these dietary changes can be transmitted from the mother to offspring during early developmental stages, subsequently influencing the predisposition to various diseases later in life. This review aims to delineate the detrimental effects of maternal urban-lifestyle diet (urbanized diet) on early-life health and gut microbiota assembly, provide mechanistic insights on how urbanized diet mediates mother-to-offspring transfer of bioactive substances in both intrauterine and extrauterine and thus affects fetal and neonatal development. Moreover, we also further propose a framework for developing microbiome-targeted precision nutrition and diet strategies specifically for pregnant and lactating women. The establishment of such knowledge can help develop proactive preventive measures from the beginning of life, ultimately reducing the long-term risk of disease and improving public health outcomes.PMID:40176259 | DOI:10.1080/19490976.2025.2483783

Microbiome. 2025 Apr 2;13(1):90. doi: 10.1186/s40168-025-02078-x.ABSTRACTBACKGROUND: The Porcine Epidemic Diarrhea Virus (PEDV) is one of the major challenges facing the global pig farming industry, and vaccines and treatments have proven difficult in controlling its spread. Faecalibacterium prausnitzii (F.prausnitzii), a key commensal bacterium in the gut, has been recognized as a promising candidate for next-generation probiotics due to its potential wide-ranging health benefits. A decrease in F.prausnitzii abundance has been associated with certain viral infections, suggesting its potential application in preventing intestinal viral infections. In this study, we utilized a piglet model to examine the potential role of F.prausnitzii in PEDV infections.RESULTS: A piglet model of PEDV infection was established and supplemented with F.prausnitzii, revealing that F.prausnitzii mitigated PEDV infection. Further studies found that outer membrane vesicles (OMVs) are the main functional components of F.prausnitzii, and proteomics, untargeted metabolomics, and small RNA-seq were used to analyze the composition of OMVs. Exhaustion of the gut microbiota demonstrated that the function of Fp. OMVs relies on the presence of the gut microbiota. Additionally, metagenomic analysis indicated that Fp. OMVs altered the gut microbiota composition, enhancing the abundance of Faecalibacterium prausnitzii, Prevotellamassilia timonensis, and Limosilactobacillus reuteri. Untargeted metabolomics analysis showed that Fp. OMVs increased phosphatidylcholine (PC) levels, with PC identified as a key metabolite in alleviating PEDV infection. Single-cell sequencing revealed that PC altered the relative abundance of intestinal cells, increased the number of intestinal epithelial cells, and reduced necroptosis in target cells. PC treatment in infected IPEC-J2 and Vero cells alleviated necroptosis and reduced the activation of the RIPK1-RIPK3-MLKL signaling axis, thereby improving PEDV infection.CONCLUSION: F.prausnitzii and its OMVs play a critical role in mitigating PEDV infections. These findings provide a promising strategy to ameliorate PEDV infection in piglets. Video Abstract.PMID:40176190 | DOI:10.1186/s40168-025-02078-x

Cardiovasc Diabetol. 2025 Apr 2;24(1):152. doi: 10.1186/s12933-025-02701-z.ABSTRACTBACKGROUND: Disruption of lipid metabolism contributes to increased cardiovascular risk in diabetes.METHODS: We evaluated the associations between serum lipidomic profile and subclinical carotid atherosclerosis (SCA) in type 1 (T1D) and type 2 (T2D) diabetes, and in subjects without diabetes (controls) in a cross-sectional study. All subjects underwent a lipidomic analysis using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry, carotid ultrasound (mode B) to assess SCA, and clinical assessment. Multiple linear regression models were used to assess the association between features and the presence and burden of SCA in subjects with T1D, T2D, and controls separately. Additionally, multiple linear regression models with interaction terms were employed to determine features significantly associated with SCA within risk groups, including smoking habit, hypertension, dyslipidaemia, antiplatelet use and sex. Depending on the population under study, different confounding factors were considered and adjusted for, including sample origin, sex, age, hypertension, dyslipidaemia, body mass index, waist circumference, glycated haemoglobin, glucose levels, smoking habit, diabetes duration, antiplatelet use, and alanine aminotransferase levels.RESULTS: A total of 513 subjects (151 T1D, 155 T2D, and 207 non-diabetic control) were included, in whom the percentage with SCA was 48.3%, 49.7%, and 46.9%, respectively. A total of 27 unique lipid species were associated with SCA in subjects with T2D, in former/current smokers with T2D, and in individuals with T2D without dyslipidaemia. Phosphatidylcholines and diacylglycerols were the main SCA-associated lipidic classes. Ten different species of phosphatidylcholines were up-regulated, while 4 phosphatidylcholines containing polyunsaturated fatty acids were down-regulated. One diacylglycerol was down-regulated, while the other 3 were positively associated with SCA in individuals with T2D without dyslipidaemia. We discovered several features significantly associated with SCA in individuals with T1D, but only one sterol could be partially annotated.CONCLUSIONS: We revealed a significant disruption of lipid metabolism associated with SCA in subjects with T2D, and a larger SCA-associated disruption in former/current smokers with T2D and individuals with T2D who do not undergo lipid-lowering treatment.PMID:40176064 | DOI:10.1186/s12933-025-02701-z