Metabolomics最新文献

{"title":"Metabolomic profiling reveals distinct and shared biology in COPD and IPF.","authors":"Aldric Rosario, Nicole Prince, Shariq Madha-Krause, Sharon M Lutz, Julian E Hecker, Jeong H Yun, Michael H Cho, Arda Halu, George R Washko, Frank C Sciurba, Lucas Barwick, Andrew H Limper, Kevin R Flaherty, Gerard J Criner, Kevin K Brown, Robert Wise, Fernando J Martinez, Russell P Bowler, Robert E Gerszten, Clary B Clish, Edwin K Silverman, Rachel S Kelly","doi":"10.1007/s11306-026-02508-3","DOIUrl":"10.1007/s11306-026-02508-3","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic Obstructive Pulmonary disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic pulmonary disorders with distinct pathologies but shared risk factors. Metabolomics may provide insights into mechanisms.</p><p><strong>Objectives: </strong>To identify metabolites associated with COPD and IPF, and to characterize shared and disease-specific signatures.</p><p><strong>Methods: </strong>Plasma metabolomic profiling was conducted in the Lung Tissue Research Consortium (LTRC). Logistic regression identified metabolites associated with COPD and IPF, and results were replicated in an external cohort, COPDGene. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to explore disease-associated metabolite modules. We further evaluated relationships between significant metabolites and risk genes of interest.</p><p><strong>Results: </strong>Of 1131 metabolites in LTRC, 246 (21.8%) differed between COPD and controls, and 136 (12.0%) between IPF and controls (FDR < 0.05). Among 80 shared significant metabolites in COPD and IPF, 77 showed concordant directions of effect. Shared metabolomic changes included reduced levels of steroids, triglycerides, diglycerides, phosphatidylcholines, and increased levels of carnitines. In contrast, polyunsaturated fatty acids, nicotine, and thyroxine metabolites differed between COPD and IPF; these findings were further explored by the WGCNA. External replication was performed for 120 metabolites measured in both cohorts, of which 49 (40.8%) replicated in COPD vs. control. In exploratory analyses leveraging quantitative imaging abnormalities (QIA) as a surrogate for IPF; only 4 (3.3%) metabolites replicated in the QIA vs. control model, and only 9 (7.5%) for COPD vs. QIA.</p><p><strong>Conclusion: </strong>Alterations in metabolomic profiles of COPD and IPF suggested shared dysregulation of several lipids. However, some metabolites pointed to disease-specific differences.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum metabolic signatures associated with maximal voluntary ventilation in native high-altitude Tibetans.","authors":"Tao Zhou, Jiawei Yang, Qiong Zhang, Haichen Zhang, Lening Chen, Shusheng Luo, Qianqian Xiao, Qinghe Meng, Jianjun Jiang, Labasangzhu Labasangzhu, Dunyou Dunyou, Danbalangjie Danbalangjie, Weidong Hao, Xuetao Wei","doi":"10.1007/s11306-026-02517-2","DOIUrl":"10.1007/s11306-026-02517-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aimed to identify serum metabolites independently associated with maximal voluntary ventilation (MVV) among native high‑altitude Tibetan adults, and explore metabolic correlates of pulmonary ventilatory function under chronic hypoxic exposure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Untargeted serum metabolomic profiling comprising 5310 initially detected metabolic features, with 3381 high-quality annotated metabolites retained after strict quality filtering and comprehensive clinical data were collected from 168 native high‑altitude Tibetan adults with complete clinical, phenotypic, and metabolomic data (no missing values in the final analytical dataset). Continuous phenotypic and metabolomic variables were Z‑score‑standardized before analysis. Participants were stratified by MVV quartiles and randomly split into a training set (70%, n = 119) and an independent validation set (30%, n = 49). A multi‑tier metabolite‑screening pipeline was implemented solely within the training set: tiered‑threshold univariate regression generated candidate metabolites, followed by elastic‑net regularized regression (α = 0.5, lambda.1se). A prespecified fallback rule selected the top‑five metabolites with the smallest univariate P‑values when elastic‑net produced no non‑zero‑coefficient features. Selected candidates were entered into confounder‑adjusted multivariable linear regression, retaining metabolites with P &lt; 0.05. Bootstrap resampling assessed screening stability. Ten‑fold cross‑validation evaluated internal performance, and the final model was tested on the independent validation set. Sensitivity analysis was performed by excluding the exogenous drug‑related metabolite to evaluate robustness of core associations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Three serum metabolites showed independent associations with MVV: N‑Undecanoylglycine (β = -5.237, P = 0.002), Isosorbide Dinitrate (β = 0.245, P = 0.007), and Hypoglycin B (β = 4.655, P = 0.006). The metabolite‑based model yielded a 10‑fold cross‑validated R&lt;sup&gt;2&lt;/sup&gt; of 0.191 in the training set, with predictive R&lt;sup&gt;2&lt;/sup&gt; decreasing to 0.090 in the independent validation set. Bootstrap inclusion frequencies for target metabolites were moderate, suggesting relatively weak marginal metabolite‑MVV effects. Sensitivity analysis confirmed that core endogenous associations were not driven by the exogenous Isosorbide Dinitrate. Formal pathway enrichment was not conducted due to the small number of significant metabolites.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study identified three serum metabolites independently correlated with MVV in native high‑altitude Tibetans using a multi‑stage metabolome‑wide screening workflow. These metabolites represent preliminary metabolic correlates of ventilatory function under chronic high‑altitude hypoxia. The marked attenuation of predictive performance from internal cross‑validation to external validation reflects limited generalisability of met","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excess glutamine rewires endothelial cell metabolism.","authors":"Marzyeh Kheradmand, Xinyao Zhou, Funke Okunrinboye, Ganesh Sriram, Alisa Morss Clyne","doi":"10.1007/s11306-026-02515-4","DOIUrl":"10.1007/s11306-026-02515-4","url":null,"abstract":"<p><strong>Introduction: </strong>Glutamine, the most abundant amino acid in the body, is a key metabolic substrate for endothelial cells. Glutamine supplementation protects against cardiovascular disease in animal models and in humans; however, glutamine in vitro has inconsistent effects on endothelial function. Furthermore, little is known about how altered metabolite concentrations, for example excess glucose in hyperglycemia or excess glutamine in cell culture media, affect endothelial cell metabolism.</p><p><strong>Objectives: </strong>The objective of this study was to determine how physiological and supplemented glutamine affect endothelial metabolism in normal and high glucose conditions.</p><p><strong>Methods: </strong>Primary human coronary artery endothelial cells were cultured in varied glutamine concentrations and in normal and high glucose. Glutamine uptake and glutamate secretion were measured using a YSI bioanalyzer; oxidative respiration was assessed using a Seahorse Metabolic Analyzer; and glutamine carbon incorporation into the TCA cycle, amino acids, antioxidants, and other pathways was evaluated via liquid chromatography-mass spectrometry.</p><p><strong>Results: </strong>As extracellular glutamine increased, endothelial cells took up more glutamine, but glutamate secretion saturated above 2 mM glutamine. Excess glutamine was primarily stored intracellularly, although increasing extracellular glutamine concentration did increase oxidative respiration and TCA cycle isotope enrichment. We also observed increased glutamine incorporation into glutathione, UDP-GlcNAc, and amino acids. When total metabolite abundance was examined, intracellular succinate, unsaturated fatty acids, and one-carbon metabolism-related metabolites decreased with increasing glutamine.</p><p><strong>Conclusion: </strong>These findings demonstrate that excess extracellular glutamine reprograms endothelial metabolism, suggesting that glutamine supplementation should be used with caution in cardiovascular therapies and endothelial cell culture.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic bisphenol A exposure at LOAEL induces hepatic metabolic remodeling associated with NAFLD-related pathways and hepatocarcinogenic susceptibility.","authors":"Ewa Lepiarczyk, Marta Wiszpolska, Mateusz A Maździarz, Krystyna Makowska, Sławomir Gonkowski, Jerzy Kaleczyc, Marta Majewska","doi":"10.1007/s11306-026-02513-6","DOIUrl":"10.1007/s11306-026-02513-6","url":null,"abstract":"<p><strong>Introduction: </strong>Bisphenol A (BPA) is a widely distributed endocrine-disrupting chemical with documented metabolic effects in experimental models. Although hepatic transcriptional alterations following BPA exposure have been reported, the extent to which these changes translate into functional metabolic remodeling remains unclear.</p><p><strong>Objectives: </strong>This study aimed to characterize global hepatic metabolomic alterations following chronic exposure to BPA at the lowest observed adverse effect level (LOAEL) in mice and to determine whether the affected metabolic networks overlap with pathways implicated in non-alcoholic fatty liver disease (NAFLD) progression and early events associated with hepatocarcinogenic susceptibility.</p><p><strong>Methods: </strong>Untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was performed on liver samples from BPA-exposed (n = 8) and control (n = 6) mice. Differential metabolite analysis and pathway enrichment analysis were conducted to identify significantly altered metabolites and metabolic pathways.</p><p><strong>Results: </strong>BPA exposure induced marked hepatic metabolic remodeling involving polyunsaturated fatty acids, arachidonic acid-derived eicosanoids, lysophospholipids, retinoid metabolism, and phase II detoxification pathways. Dysregulation of omega-3 and omega-6 fatty acids and altered prostaglandin and thromboxane derivatives indicated disruption of inflammatory lipid mediator balance. Changes in retinol- and retinoic acid-related metabolites suggested impaired differentiation-associated signaling, while increased sulfated and glucuronidated metabolites reflected enhanced xenobiotic metabolism. Pathway enrichment analysis highlighted biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and retinol metabolism as significantly affected pathways.</p><p><strong>Conclusion: </strong>Chronic BPA exposure at a LOAEL dose induces coordinated hepatic metabolic reprogramming characterized by pro-inflammatory lipid remodeling, disruption of retinoid signaling, and activation of detoxification mechanisms. These alterations may represent metabolic features associated with pathways relevant to NAFLD progression and hepatocarcinogenic susceptibility.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-species urinary metabolomics identifies 2-hydroxyisovalerate as a candidate biomarker for mtDNA-based disorders.","authors":"Marianne Venter, Karin Terburgh, Jeremie Z Lindeque, Emi Ogasawara, Mirian C H Janssen, Jan A M Smeitink, Kazuto Nakada, Roan Louw","doi":"10.1007/s11306-026-02518-1","DOIUrl":"10.1007/s11306-026-02518-1","url":null,"abstract":"<p><p>Pathogenic mitochondrial DNA (mtDNA) mutations contribute to a broad spectrum of both common and rare metabolic diseases. However, clinical presentation is highly variable and only partially explained by the proportion of mutant mtDNA or heteroplasmy. With the relationship between mutation burden and clinical manifestation poorly defined, controlled models are required to uncover underlying mechanisms. Here, we explore the metabolic consequences of increasing heteroplasmy in a well-characterised mouse model harbouring a pathogenic mtDNA deletion. Untargeted urinary metabolomics reveals distinct mutation load-dependent metabolic shifts with some metabolites declining early on, while others exhibit threshold-like increases beyond ~ 60% mutation load - the level at which lactic acidemia and OXPHOS defects become apparent in this model. To assess translational relevance, we examined these heteroplasmy-associated metabolites in urine from patients carrying the most common mtDNA mutation, m.3243 A > G. Several of these metabolites were differentially expressed in patients relative to controls, with conserved directionality across species. Among these, 2-hydroxyisovalerate (2-HIVA), which was most strongly affected in the mouse model, also emerged as the top discriminator in patients. Receiver operating characteristic analysis indicated that urinary 2-HIVA has strong discriminatory power, supporting its potential utility as a biomarker for mtDNA-based disorders. These findings enhance our understanding of mtDNA-related disease pathophysiology and establish a foundation for further validation studies.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of serum NMR metabolomics in fibrotic diseases of the myocardium.","authors":"Mark V Füzesi, Ella J Zhang, Rajshree Ghosh Biswas, Antonia Leist, Anna-Laura M Hasubek, Xiaoyu Wang, Jiashang Chen, Xin Zhou, Angela Rao, Evan Zhang, Isabella H Muti, Piet Habbel, Johannes Nowak, Leo L Cheng","doi":"10.1007/s11306-026-02512-7","DOIUrl":"10.1007/s11306-026-02512-7","url":null,"abstract":"<p><strong>Introduction: </strong>Heart failure accounts for more than 43% of annual deaths worldwide, and isdriven by widespread pathological remodeling, in which myocardial fibrosis plays an important role. Currently, accurate clinical diagnosis of myocardialfibrosis (MF) remains difficult, with even greater challenges in differentiating among lesser-understood etiologies, such as cardiac sarcoidosis (CS) andcardiac amyloidosis (CA).</p><p><strong>Objectives: </strong>To investigate the capability of high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR)spectroscopy to differentiate amongst patients with MF of different origins (CS, CA) using blood sera.</p><p><strong>Methods: </strong>HRMAS NMR spectroscopy of 10 ìL ofblood sera from three patient groups, with matched controls, was conducted:1)MF due to common causes including hypertension and coronary arterydisease (n = 13),2)transthyretin CA (n = 18), and3)CS (n = 12). NMR spectra were analyzed as regions of interest (ROIs). ROIAL-NMR was used toidentify metabolites present in the determined ROIs. Statistical analysis, such as hierarchical clustering, Wilcoxon/Kruskal-Wallis tests (paired andunpaired), and unsupervised multivariate principal component analyses (PCA), were performed to distinguish diseased individuals from their matchedcontrols.</p><p><strong>Results: </strong>Analysis of NMR spectra identified 61 ROIs highlighting metabolite alterations such as changes in fatty acids, branched chain aminoacids, and markers of energy and inflammatory states, that may contribute to disease-specific metabolic signatures.</p><p><strong>Conclusions: </strong>HRMAS NMRmetabolomics results may enhance our understanding of the patho-mechanisms underlying myocardial fibrosis across etiologies and serve as a clinicallypractical tool to improve diagnostic precision and identify new therapeutic targets.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic insights into the pathophysiology of tuberculous meningitis in FFPE postmortem human brain tissue.","authors":"Abisola R Isaiah, Du Toit Loots, Aurelia A Williams, Stefan Dan Zaharie, A Marceline Tutu van Furth, Martijn van der Kuip, Shayne Mason","doi":"10.1007/s11306-026-02511-8","DOIUrl":"10.1007/s11306-026-02511-8","url":null,"abstract":"<p><strong>Background: </strong>Tuberculous meningitis (TBM), caused by Mycobacterium tuberculosis, is the most severe form of extrapulmonary tuberculosis and isassociated with high morbidity and mortality, particularly when diagnosis is delayed. Improved understanding of the metabolic alterations associated withTBM may support the development of novel diagnostic biomarkers and provide insights into disease pathophysiology.</p><p><strong>Method: </strong>In this study, we applied anuntargeted two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) metabolomics approach to formalin-fixed, paraffin-embedded (FFPE) postmortem human brain tissue from 41 TBM cases and 36 tissue sections from 6 non-TBM control cases. Metabolomics data wereprocessed, normalized, and analyzed using multivariate and univariate statistical approaches, including principal component analysis (PCA) and partialleast squares-discriminant analysis (PLS-DA), with variable importance in projection (VIP) scores. These results were further correlated with patient clinical data.</p><p><strong>Results: </strong>Distinct metabolic profiles were observed between TBM and control tissues. Several metabolites were significantly reduced in TBM samples, particularly within the alkane and alkene classes, with additional decreases observed in metabolites associated with alcohols, fatty acids, lipids, carbohydrates, and amino acids. These metabolic alterations suggest substantial perturbations, primarily in the host lysine degradation pathway (linked to the kynurenine pathway), in TBM-affected brain tissue.</p><p><strong>Conclusion: </strong>Collectively, these findings provide insight into the metabolic landscape of terminalTBM and suggest potential metabolic pathways that may contribute to disease pathophysiology. Further investigation of these metabolic signatures in accessible patient tissue and biofluids may support the development of biomarkers and inform future therapeutic strategies for TBM.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Select plasma oxylipins as potential biomarkers of effective indomethacin treatment response in preterm infants with patent ductus arteriosus.","authors":"Khanh C K Nguyen, Cindy H T Yeung, Allison Scott, Thomas J Velenosi, Tamorah Lewis","doi":"10.1007/s11306-026-02510-9","DOIUrl":"10.1007/s11306-026-02510-9","url":null,"abstract":"<p><strong>Objectives: </strong>Patent ductus arteriosus (PDA) is one of the most common heart conditions in preterm infants, and indomethacin treatment is used for PDA closure. However, its efficacy varies among patients. This pilot study aimed to identify novel metabolic biomarkers to predict effective indomethacin response in infants with PDA.</p><p><strong>Methods: </strong>Preterm infants with PDA < 34 weeks gestational age were recruited and treated with indomethacin. Plasma and urine samples were collected before and 2-7 days after initial treatment. Longitudinal targeted oxylipin and untargeted metabolomics analysis were performed on plasma and urine samples.</p><p><strong>Results: </strong>Among 17 infants, 12 were responders and 5 non-responders to indomethacin treatment. Before the treatment, four plasma oxylipins: 12,13-DiHOME, 9,10-DiHOME, 15,16-DiHODE, and 9,10-DiHODE were significantly higher in responders compared to non-responders (P < 0.05). Following treatment, these oxylipins decreased in responders but remained stable in non-responders. Urinary 12,13-DiHOME showed an opposite trend, with lower baseline concentrations in the responders.</p><p><strong>Conclusions: </strong>Pre-treatment plasma levels of four oxylipins were associated with effective PDA response to indomethacin. The balance of oxylipins and prostaglandins is important in duct patency and may predict which infants responding to indomethacin. These pilot findings contribute to the identification of potential neonatal pharmacometabolomic biomarkers and create new hypotheses that can guide future research towards personalized PDA management in preterm infants.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted and Untargeted Urinary Metabolomic Analyses of Organophosphate Pesticides Exposure and Attention-Deficit/Hyperactivity Disorder in Children.","authors":"Hsin-Yun Tseng, Chi-Jen Lo, Boopathi Subramani, Jia-Woei Hou, Ching-Jung Yu, Ting-Yu Fang, Betau Hwang, Mei-Ling Cheng, Mei-Lien Chen","doi":"10.1007/s11306-026-02495-5","DOIUrl":"10.1007/s11306-026-02495-5","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to organophosphate pesticides (OPs) has been associated with increased oxidative stress and a higher risk of attention-deficit/hyperactivity disorder (ADHD). However, metabolic insights underlying ADHD and the potential pathophysiological role of OPs exposure remain limited.</p><p><strong>Objective: </strong>This study characterized urinary metabolomic profiles associated with ADHD and examined their associations with OPs exposure and oxidative stress.</p><p><strong>Methods: </strong>Urinary metabolites from 67 children with ADHD and 98 controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy and ultra-perforamnce liquid chromatography quadrupole time-of-flight mass spectrometry analysis (UPLC-QTOF-MS). Dimethyl phosphate (DMP) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) were used as biomarkers of OPs exposure and oxidative stress, respectively. Children were classified into high- and low-exposure/concentration groups based on DMP or HNE-MA levels.</p><p><strong>Results: </strong>Urinary metabolomic profiles differed significantly between children with ADHD and controls. Several metabolites also differed between children with high and low DMP or HNE-MA levels. Metabolites involved in the tricarboxylic acid cycle were significantly higher in ADHD children and positively correlated with both DMP and HNE-MA. Pathway analysis suggested alterations in energy-related and amino acid metabolic pathways. Stepwise logistic regression and receiver operating characteristic curve analysis identified an 11-compound biomarker panel with good discriminatory performance in the discovery (AUC: 0.8450) and validation (AUC: 0.8748) stages.</p><p><strong>Conclusion: </strong>This metabolomic analysis suggests that OPs exposure and oxidative stress may be associated with metabolic changes in ADHD, particularly in energy metabolism and amino acid pathways. The identified biomarker panel may help distinguish children with ADHD from controls. Larger studies with multiple exposure assessments are warranted.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary and cellular volatile organic compounds as biomarkers for urological cancers: a systematic review of GC-MS-based volatolomics.","authors":"Boyu Xie, Qing Wen","doi":"10.1007/s11306-026-02493-7","DOIUrl":"10.1007/s11306-026-02493-7","url":null,"abstract":"<p><strong>Introduction: </strong>Volatile organic compounds (VOCs) in human biofluids are promising non-invasive cancer biomarkers. However, their potential in urological cancers, including prostate, bladder, and kidney cancers is less explored, and the relationships between urinary and cellular VOC profiles across these cancer types remain unclear.</p><p><strong>Objectives: </strong>This systematic review aimed to evaluate gas chromatography-mass spectrometry (GC-MS)-based untargeted volatolomics studies in urological cancers to investigate cancer-specific, cross-cancer, and cross-matrix (urine vs. cell culture media) VOC biomarkers, while assessing methodological factors influencing biomarker discovery.</p><p><strong>Methods: </strong>Published urinary and cellular VOC studies in prostate, bladder, and kidney cancers were systematically reviewed. VOC biomarkers, direction of change, diagnostic performance, sampling methods, analytical platforms, compound-identification strategies, and statistical approaches were extracted and compared across cancer types and sample matrices.</p><p><strong>Results: </strong>A total of 12 urinary prostate, 9 urinary bladder, 5 urinary renal, and 3 cellular VOC studies were identified. Prostate cancer profiles were mainly characterized by decreased organic acids and alcohols, whereas bladder and renal cancers more frequently showed elevated ketones and aldehydes. Several VOCs, including 2-butanone, 2-heptanone, hexanal and phenol, were identified across multiple cancer types. Cellular studies showed consistent directional changes for six VOCs, and cross-matrix analysis identified 28 shared VOCs, seven of which showed aligned trends in urine and cell models. These findings suggest that VOCs reflect both unique and shared metabolic alterations in urological cancers and may serve as useful diagnostic biomarker candidates.</p><p><strong>Conclusion: </strong>This review integrates urinary and cellular VOC data across major urological cancers and identifies unique, recurrent, and cross-matrix VOCs that warrant further mechanistic and clinical validation. Although methodological heterogeneity remains a challenge, VOC-based approaches have generally shown good sensitivity and specificity for distinguishing malignant from healthy controls. With improved and standardized analytical methods, VOC volatolomics may support the future development of non-invasive and accurate diagnostics for urological cancers.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}