PubMed

Maternal serum metabolome and traffic-related air pollution exposure in pregnancy. Environ Int. 2019 Jun 19;130:104872 Authors: Yan Q, Liew Z, Uppal K, Cui X, Ling C, Heck JE, von Ehrenstein OS, Wu J, Walker DI, Jones DP, Ritz B Abstract BACKGROUND: Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and neurodevelopmental disorders. By utilizing high-resolution metabolomics (HRM), we investigated perturbations of the maternal serum metabolome in response to traffic-related air pollution to identify biological mechanisms. METHODS: We retrieved stored mid-pregnancy serum samples from 160 mothers who lived in the Central Valley of California known for high air particulate levels. We estimated prenatal traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 μm) during first-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) to select metabolic features associated with air pollution exposure. Pathway analyses were employed to identify biologic pathways related to air pollution exposure. As potential confounders we included maternal age, maternal race/ethnicity, and maternal education. RESULTS: In total we extracted 4038 and 4957 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for confounding factors, PLS-DA (Variable Importance in Projection (VIP) ≥2) yielded 181 and 251 metabolic features (HILIC and C18, respectively) that discriminated between the high (n = 98) and low exposed (n = 62). Pathway enrichment analysis for discriminatory features associated with air pollution indicated that in maternal serum oxidative stress and inflammation related pathways were altered, including linoleate, leukotriene, and prostaglandin pathways. CONCLUSION: The metabolomic features and pathways we found to be associated with air pollution exposure suggest that maternal exposure during pregnancy induces oxidative stress and inflammation pathways previously implicated in pregnancy complications and adverse outcomes. PMID: 31228787 [PubMed - as supplied by publisher]

Urine metabolites associated with cardiovascular effects from exposure of size-fractioned particulate matter in a subway environment: A randomized crossover study. Environ Int. 2019 Jun 19;130:104920 Authors: Zhang Y, Chu M, Zhang J, Duan J, Hu D, Zhang W, Yang X, Jia X, Deng F, Sun Z Abstract BACKGROUND: Ambient particulate matter (PM) is closely associated with morbidity and mortality from cardiovascular disease. Urine metabolites can be used as a non-invasive means to explore biological mechanisms for such associations, yet has not been performed in relation to different sizes of PM. In this randomized crossover study, we used metabolomics approach to explore the urine biomarkers linked with cardiovascular effects after PM exposure in a subway environment. METHODS AND RESULTS: Thirty-nine subjects were exposed to PM for 4 h in subway system, with either a respirator intervention phase (RIP) with facemask and no intervention phase (NIP) in random order with a 2-week washout period. Electrocardiogram (ECG) parameters and ambulatory blood pressure (BP) were monitored during the whole riding period and urine samples were collected for metabolomics analysis. After exposure to PM for 4 h in subway system, 4 urine metabolites in male and 7 urine metabolites in female were screened out by UPLC/Q-TOF MS/MS-based metabolomics approach. Cardiovascular parameters (HRV and HR) predominantly decreased in response to all size-fractions of PM and were more sensitive in response to different size-fractioned PM in males than females. Besides LF/HF, most of the HRV indices decrease induced by the increase of all size-fractioned PM while PM1.0 was found as the most influential one on indicators of cardiovascular effects and urine metabolites both genders. Prolyl-arginine and 8-OHdG were found to have opposing role regards to HRV and HR in male. CONCLUSION: Our data indicated that short-term exposure to PM in a subway environment may increase the risk of cardiovascular disease as well as affect urine metabolites in a size dependent manner (besides PM0.5), and male were more prone to trigger the cardiovascular events than female after exposure to PM; whereas wearing facemask could effectively reduce the adverse effects caused by PM. PMID: 31228782 [PubMed - as supplied by publisher]

Related Articles Comprehensive metabolomic and proteomic analyses reveal candidate biomarkers and related metabolic networks in atrial fibrillation. Metabolomics. 2019 Jun 21;15(7):96 Authors: Zhou J, Sun L, Chen L, Liu S, Zhong L, Cui M Abstract INTRODUCTION: Atrial fibrillation (AF) is an abnormal heart rhythm characterized by an irregular beating of the atria and is associated with an increased risk of heart failure, dementia, and stroke. Currently, the perturbation of plasma content due to AF disease onset is not well known. OBJECTIVES: To investigate dysregulated molecules in blood plasma of untreated AF patients, with the goal of identifying biomarkers for disease screening and pathological studies. METHODS: LC-MS based untargeted metabolomics, lipidomics and proteomics analyses were performed to find candidate biomarkers. A targeted quantification assay and an ELISA were performed to validate the results of the omics analyses. RESULTS: We found that 24 metabolites, 16 lipids and 16 proteins were significantly dysregulated in AF patients. Pathway enrichment analysis showed that the purine metabolic pathway and fatty acid metabolism were perturbed by AF onset. FA 20:2 and FA 22:4 show great linear correlational relationship with the left atrial area and could be considered for AF disease stage monitoring or prognosis evaluation. CONCLUSION: we used a comprehensive multiple-omics strategy to systematically investigate the dysregulated molecules in the plasma of AF patients, thereby revealing potential biomarkers for diagnosis and providing information for pathological studies. PMID: 31227919 [PubMed - in process]

Related Articles Metabolomics of childhood exposure to perfluoroalkyl substances: a cross-sectional study. Metabolomics. 2019 Jun 21;15(7):95 Authors: Kingsley SL, Walker DI, Calafat AM, Chen A, Papandonatos GD, Xu Y, Jones DP, Lanphear BP, Pennell KD, Braun JM Abstract INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. OBJECTIVE: To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. METHODS: We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. RESULTS: Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. CONCLUSIONS: In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health. PMID: 31227916 [PubMed - in process]

Related Articles Integrated multiomic analysis reveals comprehensive tumour heterogeneity and novel immunophenotypic classification in hepatocellular carcinomas. Gut. 2019 Jun 21;: Authors: Zhang Q, Lou Y, Yang J, Wang J, Feng J, Zhao Y, Wang L, Huang X, Fu Q, Ye M, Zhang X, Chen Y, Ma C, Ge H, Wang J, Wu J, Wei T, Chen Q, Wu J, Yu C, Xiao Y, Feng X, Guo G, Liang T, Bai X Abstract OBJECTIVE: Hepatocellular carcinoma (HCC) is heterogeneous, especially in multifocal tumours, which decreases the efficacy of clinical treatments. Understanding tumour heterogeneity is critical when developing novel treatment strategies. However, a comprehensive investigation of tumour heterogeneity in HCC is lacking, and the available evidence regarding tumour heterogeneity has not led to improvements in clinical practice. DESIGN: We harvested 42 samples from eight HCC patients and evaluated tumour heterogeneity using whole-exome sequencing, RNA sequencing, mass spectrometry-based proteomics and metabolomics, cytometry by time-of-flight, and single-cell analysis. Immunohistochemistry and quantitative polymerase chain reactions were performed to confirm the expression levels of genes. Three independent cohorts were further used to validate the findings. RESULTS: Tumour heterogeneity is considerable with regard to the genomes, transcriptomes, proteomes, and metabolomes of lesions and tumours. The immune status of the HCC microenvironment was relatively less heterogenous. Targeting local immunity could be a suitable intervention with balanced precision and practicability. By clustering immune cells in the HCC microenvironment, we identified three distinctive HCC subtypes with immunocompetent, immunodeficient, and immunosuppressive features. We further revealed the specific metabolic features and cytokine/chemokine expression levels of the different subtypes. Determining the expression levels of CD45 and Foxp3 using immunohistochemistry facilitated the correct classification of HCC patients and the prediction of their prognosis. CONCLUSION: There is comprehensive intratumoral and intertumoral heterogeneity in all dimensions of HCC. Based on the results, we propose a novel immunophenotypic classification of HCCs that facilitates prognostic prediction and may support decision making with regard to the choice of therapy. PMID: 31227589 [PubMed - as supplied by publisher]

Related Articles Evolutionary Metabolomics Identifies Substantial Metabolic Divergence between Maize and its Wild Ancestor, Teosinte. Plant Cell. 2019 Jun 21;: Authors: Xu G, Cao J, Wang X, Chen Q, Jin W, Li Z, Tian F Abstract Maize was domesticated from its wild ancestor, teosinte. Maize's new morphology and adaptation to diverse environments require coordinated changes in various metabolic pathways. However, how the metabolome was reshaped since domestication remains poorly understood. Here, we report a comprehensive assessment of divergence in the seedling metabolome between maize and teosinte. A total of 461 metabolites exhibited significant divergence due to selection. Interestingly, teosinte, tropical and temperate maize, representing major stages of maize evolution, targeted distinct sets of metabolites. Alkaloids, terpenoids and lipids were specifically targeted in the divergence between teosinte and tropical maize, while benzoxazinoids were specifically targeted in the divergence between tropical and temperate maize. To identify genetic factors controlling metabolic divergence, we assayed the seedling metabolome of a large maize-by-teosinte cross population. We show that the recent metabolic divergence between tropical and temperate maize tended to have simpler genetic architecture than the divergence between teosinte and tropical maize. Through integrating transcriptome data, we identified candidate genes contributing to metabolic divergence, many of which were under selection at nucleotide and transcript levels. Through overexpression or mutant analysis, we verified the roles of FHT1, Pr1, and ZmTPS1 in the divergence of their related biosynthesis pathways. Our findings not only provide important insights into domestication-associated changes in metabolism but also highlight the power of combining omics data for trait dissection. PMID: 31227559 [PubMed - as supplied by publisher]

Related Articles Polycyclic aromatic compounds in urban air and associated inhalation cancer risks: A case study targeting distinct source sectors. Environ Pollut. 2019 Jun 06;: Authors: Jariyasopit N, Tung P, Su K, Halappanavar S, Evans GJ, Su Y, Khoomrung S, Harner T Abstract Passive air sampling was conducted in Toronto and the Greater Toronto Area from 2016 to 2017 for 6 periods, in order to investigate ambient levels of polycyclic aromatic compounds (PACs) associated with different source types. The selected sampling sites (n = 8) cover geographical areas with varying source emissions including background, traffic, urban, industrial and residential sites. Passive air samples were analyzed for PACs which include PAHs, alkylated PAHs (alk-PAHs), dibenzothiophene and alkylated dibenzothiophenes (DBTs) and results for PAHs were used to calculate inhalation cancer risks using different approaches. The samples were also characterized for PAH derivatives including nitrated PAHs (NPAHs) and oxygenated PAHs (OPAHs). Concentrations of Σalk-PAHs and DBTs, which are known to be enriched in fossil fuels, as well as ΣNPAHs, were highest at a traffic site (MECP) located adjacent to the 18-lane Highway 401 that runs across Toronto. Except for an industrial site (HH/BU), PAC compositions were similar across the sampling sites with Σalk-PAHs being the most abundant class of PACs suggesting traffic emission was a major contributor to PACs in the atmosphere of Toronto. The industrial site exhibited a distinct chemical composition with ΣPAHs dominating over Σalk-PAHs and with elevated levels of fluoranthene, 9-nitroanthracene, and 9,10-anthraquinone, which likely reflects emissions from nearby industrial sources. MECP and HH/BU exhibited higher lifetime excess inhalation cancer risks indicating an association with traffic and industrial sources. The importance of the traffic sector as a source of PACs to ambient air is further supported by strong correlations of the ΣPAHs, Σalk-PAHs, DBTs, and ΣOPAHs with NOx. This study highlights the importance of traffic as an emission source of PACs to urban air and the relevance of PAC classes other than just unsubstituted PAHs that are important but currently not included in air quality guidelines or for assessing inhalation cancer risks. PMID: 31227350 [PubMed - as supplied by publisher]

Related Articles Effectiveness of a muticomponent workout program integrated in an evidence based multimodal program in hyperfrail elderly patients: POWERAGING randomized clinical trial protocol. BMC Geriatr. 2019 Jun 21;19(1):171 Authors: González-Sánchez M, Cuesta-Vargas AI, Del Mar Rodríguez González M, Caro ED, Núñez GO, Galán-Mercant A, Belmonte JJB Abstract BACKGROUND: Short-term and mid-term comparison of the efficacy of a multimodal program that incorporates a therapeutic workout program, medication review, diet adjustment and health education, in comparison to the standard medical practice in the improvement of the neuromuscular and physiological condition. Furthermore, it is intended to analyse the maintenance of these effects in a long-term follow-up (12 months) from the onset of the intervention. METHODS: A randomized clinical trial of elderly frail patients drawn from the Clinical Management Unit "Tiro de Pichón", Health District of Malaga, will be included in the study (after meeting the inclusion / exclusion criteria) will be randomized in two groups: a control group that will undergo an intervention consistent of medication review + diet adjustment + health education (regular workout recommendations within a complete advice on healthy lifestyles) and an experimental group whose intervention will consist of a multimodal treatment: therapeutic workout program+ medication review+ diet adjustment + health education. The sociodemographic, clinical and tracing variables will be reflected at the beginning of the study. In addition, the follow-up variables will be gathered at the second and sixth months after the beginning of the treatment and at the third and sixth months after the treatment (follow-up). The follow-up variables that will be measured are: body mass index, general health condition, fatigue, frailty, motor control, attention- concentration- memory, motor memory, spatial orientation, grip strength, balance (static, semi-dynamic), gait speed and metabolomics. A descriptive analysis of the sociodemographic variables of the participants will be conducted. One-Factor ANOVA will be used for the Within-Subject analysis and as for the Between-Subject analysis, the outcome variables between both the groups in each moment of the data collection will be compared. DISCUSSION: A multimodal program that incorporates a therapeutic workout program, medication review, diet adjustment and health education may be effective treatment to reduce the functional decline in elderly. The results of the study will provide information on the possible strengths and benefits in multimodal program in elderly. TRIAL REGISTRATION: ClinicalTrials.gov NCT02772952 registered May 2017. PMID: 31226936 [PubMed - in process]

Related Articles A Quantitative HILIC-MS/MS Assay of the Metabolic Response of Huh-7 Cells Exposed to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. Metabolites. 2019 Jun 20;9(6): Authors: Liu Q, Cai J, Nichols RG, Tian Y, Zhang J, Smith PB, Wang Y, Yan C, Patterson AD Abstract A hydrophilic interaction liquid chromatography (HILIC)-ultra high-pressure liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS) method was developed and applied to profile metabolite changes in human Huh-7 cells exposed to the potent aryl hydrocarbon receptor (AHR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Comparisons of sensitivity (limit of detection as low as 0.01 µM) and reproducibility (84% of compounds had an interday relative standard deviation (RSD) less than 10.0%; 83% of compounds had an intraday RSD less than 15.0%) were assessed for all the metabolites. The exposure of Huh-7 cells to the hepatotoxic carcinogen TCDD at low doses (1 nM and 10 nM for 4 h and 24 h, respectively) was reflected by the disturbance of amino acid metabolism, energy metabolism (glycolysis, TCA cycle), and nucleic acid metabolism. TCDD caused a significant decrease in amino acids such as serine, alanine, and proline while promoting an increase in arginine levels with 24 h treatment. Energy metabolism intermediates such as phosphoenolpyruvate and acetyl-CoA and nucleosides such as UMP, XMP, and CMP were also markedly decreased. These results support the application of HILIC-UHPLC-MS/MS for robust and reliable analysis of the cellular response to environmentally relevant toxicants at lower doses. PMID: 31226775 [PubMed]

59 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

59 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Metabolomic Insights into the Effects of Breast Milk Versus Formula Milk Feeding in Infants. Curr Nutr Rep. 2019 Jun 15;: Authors: Phan M, Momin SR, Senn MK, Wood AC Abstract PURPOSE OF REVIEW: This review summarizes the latest scientific evidence for the presence of metabolomic differences between infants fed breast milk (I-BM) and infants fed formula milk (I-FM). RECENT FINDINGS: Across the studies included in this review, a total of 261 metabolites were analyzed, of which 151 metabolites were reported as significantly associated with infant feeding modality (BM versus FM). However, taken as a whole, the relevant literature was notable both for methodological limitations, such as small sample sizes, and heterogeneity between the studies. This may be why many associations between infant metabolite profile and feeding modality have not replicated across studies. To our knowledge, this is the first review to integrate the available literature on metabolomic differences between I-BM versus I-FM. This narrative review synthesized the data across studies and identified those metabolites which show the most robust associations with infant feeding modality. Methodological limitations of the current studies are identified, followed by recommendations for how to address these in future studies. PMID: 31203566 [PubMed - as supplied by publisher]

Related Articles Metabolite signatures of grasspea suspension-cultured cells illustrate the complexity of dehydration response. Planta. 2019 Jun 15;: Authors: Rathi D, Pareek A, Zhang T, Pang Q, Chen S, Chakraborty S, Chakraborty N Abstract MAIN CONCLUSION: This represents the first report deciphering the dehydration response of suspension-cultured cells of a crop species, highlighting unique and shared pathways, and adaptive mechanisms via profiling of 330 metabolites. Grasspea, being a hardy legume, is an ideal model system to study stress tolerance mechanisms in plants. In this study, we investigated the dehydration-responsive metabolome in grasspea suspension-cultured cells (SCCs) to identify the unique and shared metabolites crucial in imparting dehydration tolerance. To reveal the dehydration-induced metabolite signatures, SCCs of grasspea were exposed to 10% PEG, followed by metabolomic profiling. Chromatographic separation by HPLC coupled with MRM-MS led to the identification of 330 metabolites, designated dehydration-responsive metabolites (DRMs), which belonged to 28 varied functional classes. The metabolome was found to be constituted by carboxylic acids (17%), amino acids (13.5%), flavonoids (10.9%) and plant growth regulators (10%), among others. Pathway enrichment analysis revealed predominance of metabolites involved in phytohormone biosynthesis, secondary metabolism and osmotic adjustment. Exogenous application of DRMs, arbutin and acetylcholine, displayed improved physiological status in stress-resilient grasspea as well as hypersensitive pea, while administration of lauric acid imparted detrimental effects. This represents the first report on stress-induced metabolomic landscape of a crop species via a suspension culture system, which would provide new insights into the molecular mechanism of stress responses and adaptation in crop species. PMID: 31203447 [PubMed - as supplied by publisher]

Related Articles Study of BDE-47 induced Parkinson's disease-like metabolic changes in C57BL/6 mice by integrated metabolomic, lipidomic and proteomic analysis. J Hazard Mater. 2019 Jun 06;378:120738 Authors: Ji F, Sreenivasmurthy SG, Wei J, Shao X, Luan H, Zhu L, Song J, Liu L, Li M, Cai Z Abstract As the predominant congener of polybrominated diphenyl ethers (PBDEs) detected in human serum, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) has been reported to induce neurotoxicity. However, the possible linkage between BDE-47 and typical neurodegenerative diseases such as Parkinson's disease (PD) is still unclear. Here we carried out omics studies using liquid chromatography-orbitrap mass spectrometry (LC-orbitrap MS) to depict the BDE-47 induced metabolic changes in C57BJ/L mice to explore the possible contribution of BDE-47 exposure to PD pathology. BDE-47 dissolved in corn oil was orally administered to mice for 30 consecutive days. Results of metabolomics and lipidomics studies of PD-related brain regions revealed significant metabolite changes in pathways involved in oxidative stress and neurotransmitter production. Moreover, isobaric tags for relative and absolute quantitation (iTRAQ) proteomics study of the striatum, which is the part of brain that is most intensively studied in PD pathogenesis, revealed that BDE-47 could induce neurotransmitter system disturbance, abnormal phosphorylation, mitochondrial dysfunction and oxidative stress. Overall, this study depicts the possible contribution of BDE-47 exposure to PD pathology and highlights the powerfulness of omics platforms to deepen the mechanistic understanding of environmental pollutant-caused toxicity. PMID: 31203119 [PubMed - as supplied by publisher]