PubMed

Related Articles Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging. Am J Physiol Renal Physiol. 2016 May 15;310(10):F1136-47 Authors: Rao S, Walters KB, Wilson L, Chen B, Bolisetty S, Graves D, Barnes S, Agarwal A, Kabarowski JH Abstract Acute kidney injury (AKI) is one of the leading causes of in-hospital morbidity and mortality, particularly in critically ill patients. Although our understanding of AKI at the molecular level remains limited due to its complex pathophysiology, recent advances in both quantitative and spatial mass spectrometric approaches offer new opportunities to assess the significance of renal metabolomic changes in AKI models. In this study, we evaluated lipid changes in early ischemia-reperfusion (IR)-related AKI in mice by using sequential window acquisition of all theoretical spectra (SWATH)-mass spectrometry (MS) lipidomics. We found a significant increase in two abundant ether-linked phospholipids following IR at 6 h postinjury, a plasmanyl choline, phosphatidylcholine (PC) O-38:1 (O-18:0, 20:1), and a plasmalogen, phosphatidylethanolamine (PE) O-42:3 (O-20:1, 22:2). Both of these lipids correlated with the severity of AKI as measured by plasma creatinine. In addition to many more renal lipid changes associated with more severe AKI, PC O-38:1 elevations were maintained at 24 h post-IR, while renal PE O-42:3 levels decreased, as were all ether PEs detected by SWATH-MS at this later time point. To further assess the significance of this early increase in PC O-38:1, we used matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to determine that it occurred in proximal tubules, a region of the kidney that is most prone to IR injury and also rich in the rate-limiting enzymes involved in ether-linked phospholipid biosynthesis. Use of SWATH-MS lipidomics in conjunction with MALDI-IMS for lipid localization will help in elucidating the role of lipids in the pathobiology of AKI. PMID: 26911846 [PubMed - indexed for MEDLINE]

24 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 2017/06/27PubMed 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.

Systematic biobanking, novel imaging techniques, and advanced molecular analysis for precise tumor diagnosis and therapy: The Polish MOBIT project. Adv Med Sci. 2017 Jun 21;62(2):405-413 Authors: Niklinski J, Kretowski A, Moniuszko M, Reszec J, Michalska-Falkowska A, Niemira M, Ciborowski M, Charkiewicz R, Jurgilewicz D, Kozlowski M, Ramlau R, Piwkowski C, Kwasniewski M, Kaczmarek M, Ciereszko A, Wasniewski T, Mroz R, Naumnik W, Sierko E, Paczkowska M, Kisluk J, Sulewska A, Cybulski A, Mariak Z, Kedra B, Szamatowicz J, Kurzawa P, Minarowski L, Charkiewicz AE, Mroczko B, Malyszko J, Manegold C, Pilz L, Allgayer H, Abba ML, Juhl H, Koch F, MOBIT Study Group Abstract Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized. The continued identification of new genes and biomarkers specific to disease subtypes and individual patients is essential and inevitable for translation into personalized medicine, in estimating both, disease risk and response to therapy. Taking into consideration the mostly unsolved necessity of tailored therapy in oncology the innovative project MOBIT (molecular biomarkers for individualized therapy) was designed. The aims of the project are: (i) establishing integrative management of precise tumor diagnosis and therapy including systematic biobanking, novel imaging techniques, and advanced molecular analysis by collecting comprehensive tumor tissues, liquid biopsies (whole blood, serum, plasma), and urine specimens (supernatant; sediment) as well as (ii) developing personalized lung cancer diagnostics based on tumor heterogeneity and integrated genomics, transcriptomics, metabolomics, and radiomics PET/MRI analysis. It will consist of 5 work packages. In this paper the rationale of the Polish MOBIT project as well as its design is presented. (iii) The project is to draw interest in and to invite national and international, private and public, preclinical and clinical initiatives to establish individualized and precise procedures for integrating novel targeted therapies and advanced imaging techniques. PMID: 28646744 [PubMed - as supplied by publisher]

Related Articles Metabolomics of Diabetes in Pregnancy. Curr Diab Rep. 2017 Aug;17(8):57 Authors: McCabe CF, Perng W Abstract PURPOSE OF REVIEW: The purpose of this review is to describe ways in which metabolomics may enhance understanding of gestational diabetes mellitus (GDM) etiology and refine current diagnostic criteria. RECENT FINDINGS: Current clinical recommendations suggest screening for GDM between 24 and 28 of gestational weeks using an oral glucose tolerance test. Despite this consensus, there are discrepancies regarding the exact criteria for GDM diagnosis. Further, emerging evidence has unveiled heterogeneous physiological pathways underlying GDM-specifically, GDM with defective insulin secretion vs. sensitivity-that have important implications for disease diagnosis and management. The objectives of this review are threefold. First, we seek to provide a brief summary of current knowledge regarding GDM pathophysiology. Next, we describe the potential role of metabolomics to refine and improve the prediction, screening, and diagnosis of GDM. Finally, we propose ways in which metabolomics may eventually impact clinical care and risk assessment for GDM and its comorbidities. PMID: 28646358 [PubMed - in process]

Related Articles Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats. Cancer Chemother Pharmacol. 2017 Jun 23;: Authors: Forsgård RA, Marrachelli VG, Korpela K, Frias R, Collado MC, Korpela R, Monleon D, Spillmann T, Österlund P Abstract PURPOSE: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. METHODS: A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance ((1)H-NMR). RESULTS: Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. CONCLUSIONS: Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes. PMID: 28646338 [PubMed - as supplied by publisher]

Related Articles Metabolic Reprogramming via PPARα Signaling in Cardiac Hypertrophy and Failure From Metabolomics to Epigenetics. Am J Physiol Heart Circ Physiol. 2017 Jun 23;:ajpheart.00103.2017 Authors: Warren JS, Oka SI, Zablocki D, Sadoshima J Abstract Studies using -omics-based approaches have advanced our knowledge of metabolic remodeling in cardiac hypertrophy and failure. Metabolomic analysis of the failing heart has revealed global changes in mitochondrial substrate metabolism. Peroxisome proliferator-activated receptor alpha (PPARα) plays a critical role in synergistic regulation of cardiac metabolism through transcriptional control. Metabolic reprogramming via PPARα signaling in heart failure ultimately propagates into myocardial energetics. However, emerging evidence suggests that the expression level of PPARα per se does not always explain the energetic state in the heart. The transcriptional activities of PPARα are dynamic, yet highly coordinated. An additional level of complexity in the PPARα regulatory mechanism arises from its ability to interact with various partners, which ultimately determines the metabolic phenotype of the diseased heart. This review summarizes our current knowledge of the PPARα regulatory mechanisms in cardiac metabolism and the possible role of PPARα in epigenetic modifications in the diseased heart. In addition, we discuss how metabolomics can contribute to a better understanding of the role of PPARα in the progression of cardiac hypertrophy and failure. PMID: 28646024 [PubMed - as supplied by publisher]

Related Articles Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets. Free Radic Biol Med. 2017 Jun 20;: Authors: McDougall M, Choi J, Truong L, Tanguay R, Traber MG Abstract Vitamin E (α-tocopherol; VitE) is a lipophilic antioxidant required for normal embryonic development in vertebrates, but the long-term effects of embryonic VitE deficiency, and whether they are ameliorated by feeding VitE-adequate diets, remain unknown. We addressed these questions using a zebrafish (Danio rerio) model of developmental VitE deficiency followed by dietary remediation. Adult zebrafish maintained on VitE-deficient (E-) or sufficient (E+) diets were spawned to obtained E- and E+ embryos, respectively, which we evaluated up to 12 days post-fertilization (dpf). The E- group suffered significantly increased morbidity and mortality as well as altered DNA methylation status through 5 dpf when compared to E+ larvae, but upon feeding with a VitE-adequate diet from 5-12 dpf both the E- and E+ groups survived and grew normally; the DNA methylation profile also was similar between groups by 12 dpf. However, 12 dpf E- larvae still had behavioral defects. These observations coincided with sustained VitE deficiency in the E- vs. E+ larvae (p< 0.0001), despite adequate dietary supplementation. We also found in E- vs. E+ larvae continued docosahexaenoic acid (DHA) depletion (p< 0.0001) and significantly increased lipid peroxidation. Further, targeted metabolomics analyses revealed persistent dysregulation of the cellular antioxidant network, the CDP-choline pathway, and glucose metabolism. While anaerobic processes were increased, aerobic metabolism was decreased in the E- vs. E+ larvae, indicating mitochondrial damage. Taken together, these outcomes suggest embryonic VitE deficiency causes lasting behavioral impairments due to persistent lipid peroxidation and metabolic perturbations that are not resolved via later dietary VitE supplementation. PMID: 28645790 [PubMed - as supplied by publisher]

Related Articles AKR1C3-mediated adipose androgen generation drives lipotoxicity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017 Jun 22;: Authors: O'Reilly MW, Kempegowda P, Walsh M, Taylor AE, Manolopoulos KN, Allwood JW, Semple RK, Hebenstreit D, Dunn WB, Tomlinson JW, Arlt W Abstract Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder, occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS. Methods: We performed a human deep metabolic in vivo phenotyping study, examining the systemic and intra-adipose effects of acute and chronic androgen exposure in ten PCOS women, in comparison to ten body mass index-matched healthy controls, complemented by in vitro experiments. Results: PCOS women had increased intra-adipose concentrations of testosterone (p=0.0006) and dihydrotestosterone (p=0.01), with increased expression of the androgen-activating enzyme aldo-ketoreductase type 1 C3 (AKR1C3, p=0.04) in subcutaneous adipose tissue. Adipose glycerol levels in subcutaneous adipose tissue microdialysate supported in vivo suppression of lipolysis after acute androgen exposure in PCOS (p=0.04). Mirroring this, non-targeted serum metabolomics revealed pro-lipogenic effects of androgens in PCOS women only. In vitro studies showed that insulin increased adipose AKR1C3 expression and activity while androgen exposure increased adipocyte de novo lipid synthesis. Pharmacological AKR1C3 inhibition in vitro decreased de novo lipogenesis. Conclusions: These findings define a novel intra-adipose mechanism of androgen activation that contributes to adipose remodelling and a systemic lipotoxic metabolome, with intra-adipose androgens driving lipid accumulation and insulin resistance in PCOS. AKR1C3 represents a promising novel therapeutic target in PCOS. PMID: 28645211 [PubMed - as supplied by publisher]

Related Articles System-wide analysis of short-term response to high temperature in Pinus radiata. J Exp Bot. 2017 Jun 22;: Authors: Escandón M, Valledor L, Pascual J, Pinto G, Cañal MJ, Meijón M Abstract Pinus radiata seedlings, the most widely planted pine species in the world, were exposed to temperatures within a range mimicking future scenarios based on current models of heat increase. The short-term heat response in P. radiata was studied in detail by exploring the metabolome, proteome and targeted transcriptome. The use of complementary mass spectrometry techniques, GC-MS and LC-Orbitrap-MS, together with novel bioinformatics tools allowed the reliable quantification of 2,075 metabolites and 901 protein groups. Integrative analyses of different functional levels and plant physiological status revealed a complex molecular interaction network of positive and negative correlations between proteins and metabolites involved in short-term heat response, including three main physiological functions as: 1) A hormone subnetwork, where fatty acids, flavonoids and hormones presented a key role; 2) An oxidoreductase subnetwork, including several dehydrogenase and peroxidase proteins; and 3) A heat shock protein subnetwork, with numerous proteins that contain a HSP20 domain, all of which were overexpressed at the transcriptional level. Integrated analysis pinpointed the basic mechanisms underlying the short-term physiological reaction of P. radiata during heat response. This approach was feasible in forest species and unmasked two novel candidate biomarkers of heat resistance, PHO1 and TRANSCRIPTION FACTOR APFI, and a MITOCHONDRIAL SMALL HEAT SHOCK PROTEIN, for use in future breeding programs. PMID: 28645179 [PubMed - as supplied by publisher]

33 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 2017/06/24PubMed 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.

Covalent attachment and Pro-Pro endopeptidase (PPEP-1)-mediated release of Clostridium difficile cell surface proteins involved in adhesion. Mol Microbiol. 2017 Jun 21;: Authors: Corver J, Cordo' V, van Leeuwen HC, Klychnikov OI, Hensbergen PJ Abstract In the past decade, Clostridium difficile has emerged as an important gut pathogen. This anaerobic, Gram-positive bacterium is the main cause of infectious nosocomial diarrhea. Whereas much is known about the mechanism through which the C. difficile toxins cause diarrhea, relatively little is known about the dynamics of adhesion and motility, which is mediated by cell surface proteins. This review will discuss the recent advances in our understanding of the sortase-mediated covalent attachment of cell surface (adhesion) proteins to the peptidoglycan layer of C. difficile and their release through the action of a highly specific secreted metalloprotease (Pro-Pro endopeptidase 1, PPEP-1). Specific emphasis will be on a model in which PPEP-1 and its substrates control the switch from a sessile to motile phenotype in C. difficile, and how this is regulated by the cyclic dinucleotide c-di-GMP (3'-5' cyclic dimeric guanosine monophosphate). This article is protected by copyright. All rights reserved. PMID: 28636257 [PubMed - as supplied by publisher]

Evaluation of Classifier Performance for Multiclass Phenotype Discrimination in Untargeted Metabolomics. Metabolites. 2017 Jun 21;7(2): Authors: Trainor PJ, DeFilippis AP, Rai SN Abstract Statistical classification is a critical component of utilizing metabolomics data for examining the molecular determinants of phenotypes. Despite this, a comprehensive and rigorous evaluation of the accuracy of classification techniques for phenotype discrimination given metabolomics data has not been conducted. We conducted such an evaluation using both simulated and real metabolomics datasets, comparing Partial Least Squares-Discriminant Analysis (PLS-DA), Sparse PLS-DA, Random Forests, Support Vector Machines (SVM), Artificial Neural Network, k-Nearest Neighbors (k-NN), and Naïve Bayes classification techniques for discrimination. We evaluated the techniques on simulated data generated to mimic global untargeted metabolomics data by incorporating realistic block-wise correlation and partial correlation structures for mimicking the correlations and metabolite clustering generated by biological processes. Over the simulation studies, covariance structures, means, and effect sizes were stochastically varied to provide consistent estimates of classifier performance over a wide range of possible scenarios. The effects of the presence of non-normal error distributions, the introduction of biological and technical outliers, unbalanced phenotype allocation, missing values due to abundances below a limit of detection, and the effect of prior-significance filtering (dimension reduction) were evaluated via simulation. In each simulation, classifier parameters, such as the number of hidden nodes in a Neural Network, were optimized by cross-validation to minimize the probability of detecting spurious results due to poorly tuned classifiers. Classifier performance was then evaluated using real metabolomics datasets of varying sample medium, sample size, and experimental design. We report that in the most realistic simulation studies that incorporated non-normal error distributions, unbalanced phenotype allocation, outliers, missing values, and dimension reduction, classifier performance (least to greatest error) was ranked as follows: SVM, Random Forest, Naïve Bayes, sPLS-DA, Neural Networks, PLS-DA and k-NN classifiers. When non-normal error distributions were introduced, the performance of PLS-DA and k-NN classifiers deteriorated further relative to the remaining techniques. Over the real datasets, a trend of better performance of SVM and Random Forest classifier performance was observed. PMID: 28635678 [PubMed - in process]

The protein Slr1143 is an active diguanylate cyclase in Synechocystis sp. PCC 6803 and interacts with the photoreceptor Cph2. Microbiology. 2017 Jun 21;: Authors: Angerer V, Schwenk P, Wallner T, Kaever V, Hiltbrunner A, Wilde A Abstract Cyclic-di-GMP is an ubiquitous second messenger in bacteria. Several c-di-GMP receptor proteins have been identified to date, and downstream signalling pathways are often mediated through protein-protein interactions. The photoreceptor Cph2 from the cyanobacterium Synechocystis sp. PCC 6803 comprises three domains related to c-di-GMP metabolism: two GGDEF and one EAL domain. It has been shown that the C-terminal GGDEF domain acts as blue-light triggered c-di-GMP producer thereby inhibiting motility of the cells in blue light. The specific function of the other two c-di-GMP related domains remained unclear. In this study, we test knockout mutants of potential interaction partners of Cph2 for altered phototactic behaviour. Whereas wild-type cells are non-motile under high-intensity red light of 640 nm, the mutant Δslr1143 displays positive phototaxis. This phenotype can be complemented by overexpression of full-length Slr1143, which also results in an increased cellular c-di-GMP concentration. However, the non-motile phenotype of wild-type cells under high-intensity red light appears not to be due to an elevated cellular c-di-GMP content. Using co-precipitation and yeast two-hybrid assays, we demonstrate that the GGDEF domain of Slr1143 interacts with the EAL and the GGDEF domains of Cph2. However, under the test conditions, the interaction of the two proteins is not light-dependent. We conclude that Slr1143 is a new Cph2-interacting regulatory factor which modulates motility under red light and accordingly we propose Cip1 (Cph2-interacting protein 1) as a new designation for this gene product. PMID: 28635593 [PubMed - as supplied by publisher]

Anti-adhesive Activity and Metabolomics Analysis of Rat Urine After Cranberry (Vaccinium macrocarpon Aiton) Administration. J Agric Food Chem. 2017 Jun 21;: Authors: Peron G, Anna P, Paola B, Schievano E, Mammi S, Sut S, Castagliuolo I, Dall'Acqua S Abstract Cranberry (Vaccinium macrocarpon Aiton) is used to treat non-complicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents being able to inhibit bacterial adhesion to the urinary epithelium. However, there are doubts about PAC-A role in UTIs, due to their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion and contradictory clinical trials. The effects of 35 days cranberry (11 mg/kg PAC-A, 4 mg/kg PAC-B) supplementation were studied in healthy rats using a UPLC-MS-based metabolomics approach. Microbial PACs metabolites, as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8 and 24 hours after cranberry intake and their anti-adhesive properties were tested against uropathogenic Escherichia coli. The 8 hours samples presented the highest activity. Changes in urinary composition were studied by UPLC-QTOF, observing the presence of PACs metabolites. Furthermore, PAC-A2 levels were measured in all collected samples, allowing the detection of ng/mL levels in the 4 hours ones, being the highest amounts found. Results indicate that anti-adhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to direct PAC-A effect, being the measured PAC-A levels in urine lower than those reported as active in literature. PMID: 28635280 [PubMed - as supplied by publisher]

Related Articles Metabolomic Analysis and Mode of Action of Metabolites of Tea Tree Oil Involved in the Suppression of Botrytis cinerea. Front Microbiol. 2017;8:1017 Authors: Xu J, Shao X, Li Y, Wei Y, Xu F, Wang H Abstract Tea tree oil (TTO), a volatile essential oil, has been widely used as an antimicrobial agent. However, the mechanism underlying TTO antifungal activity is not fully understood. In this study, a comprehensive metabolomics survey was undertaken to identify changes in metabolite production in Botrytis cinerea cells treated with TTO. Significant differences in 91 metabolites were observed, including 8 upregulated and 83 downregulated metabolites in TTO-treated cells. The results indicate that TTO inhibits primary metabolic pathways through the suppression of the tricarboxylic acid (TCA) cycle and fatty acid metabolism. Further experiments show that TTO treatment decreases the activities of key enzymes in the TCA cycle and increases the level of hydrogen peroxide (H2O2). Membrane damage is also induced by TTO treatment. We hypothesize that the effect of TTO on B. cinerea is achieved mainly by disruption of the TCA cycle and fatty acid metabolism, resulting in mitochondrial dysfunction and oxidative stress. PMID: 28634477 [PubMed - in process]

Related Articles Fetal metabolic stress disrupts immune homeostasis and induces pro-inflammatory responses in HIV-1 and cART-exposed infants. J Infect Dis. 2017 Jun 17;: Authors: Schoeman JC, Moutloatse GP, Harms AC, Vreeken RJ, Scherpbier HJ, Van Leeuwen L, Kuijpers TW, Reinecke CJ, Berger R, Hankemeier T, Bunders MJ Abstract Increased morbidity and fetal growth restriction are reported in uninfected children born to HIV-1-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART)-exposure on the infants' immune-metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning. The lipid metabolism was further dysregulated with increased triglyceride species and a subsequent decrease in phospholipids in cART/HIV-1-exposed infants compared to control infants. Pro-inflammatory immune mediators, lysophospholipids as well as cytokines such as CXCL10 and CCL3 were increased while anti-inflammatory metabolites from cytochrome P450 pathway were reduced in cART/HIV-1-exposed infants. Taken together, these data demonstrate that the fetal metabolism is impacted by maternal factors (cART and HIV-1) and skews physiological immune responses towards inflammation in the newborn infant. PMID: 28633455 [PubMed - as supplied by publisher]

Related Articles Neonatal Metabolomic Profiles Related to Prenatal Arsenic Exposure. Environ Sci Technol. 2017 Jan 03;51(1):625-633 Authors: Laine JE, Bailey KA, Olshan AF, Smeester L, Drobná Z, Stýblo M, Douillet C, García-Vargas G, Rubio-Andrade M, Pathmasiri W, McRitchie S, Sumner SJ, Fry RC Abstract Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in Gómez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure. PMID: 27997141 [PubMed - indexed for MEDLINE]

Related Articles Current LC-MS methods and procedures applied to the identification of new steroid metabolites. J Steroid Biochem Mol Biol. 2016 Sep;162:41-56 Authors: Marcos J, Pozo OJ Abstract The study of the metabolism of steroids has a long history; from the first characterizations of the major metabolites of steroidal hormones in the pre-chromatographic era, to the latest discoveries of new forms of excretions. The introduction of mass spectrometers coupled to gas chromatography at the end of the 1960's represented a major breakthrough for the elucidation of new metabolites. In the last two decades, this technique is being complemented by the use of liquid chromatography-mass spectrometry (LC-MS). In addition of becoming fundamental in clinical steroid determinations due to its excellent specificity, throughput and sensitivity, LC-MS has emerged as an exceptional tool for the discovery of new steroid metabolites. The aim of the present review is to provide an overview of the current LC-MS procedures used in the quest of novel metabolic products of steroidal hormones and exogenous steroids. Several aspects regarding LC separations are first outlined, followed by a description of the key processes that take place in the mass spectrometric analysis, i.e. the ionization of the steroids in the source and the fragmentation of the selected precursor ions in the collision cell. The different analyzers and approaches employed together with representative examples of each of them are described. Special emphasis is placed on triple quadrupole analyzers (LC-MS/MS), since they are the most commonly employed. Examples on the use of precursor ion scan, neutral loss scan and theoretical selected reaction monitoring strategies are also explained. PMID: 26709140 [PubMed - indexed for MEDLINE]

16 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 2017/06/21PubMed 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.

25 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 2017/06/20PubMed 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.