Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 16 min 38 sec ago

Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke.

Fri, 11/05/2018 - 15:00
Related Articles Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke. J Appl Physiol (1985). 2017 Sep 01;123(3):544-557 Authors: Audet GN, Dineen SM, Stewart DA, Plamper ML, Pathmasiri WW, McRitchie SL, Sumner SJ, Leon LR Abstract It has been suggested that medications can increase heat stroke (HS) susceptibility/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (Tc) of male, C57BL/6J mice (n = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg/kg or high dose (HI) 5 mg/kg in flavored treat] or vehicle (flavored treat) before heating. HS animals were heated to 42.4°C and euthanized at three time points for histological, molecular, and metabolic analysis: onset of HS [maximal core temperature (Tc,Max)], 3 h of recovery [minimal core temperature or hypothermia depth (HYPO)], and 24 h of recovery (24 h). Nonheated (control) animals underwent identical treatment in the absence of heat. INDO (LO or HI) had no effect on physiological indicators of performance (e.g., time to Tc,Max, thermal area, or cooling time) during heating or recovery. HI INDO resulted in 45% mortality rate by 24 h (HI INDO + HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO + HS in both survivors and nonsurvivors. HI INDO + HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at Tc,Max, HYPO, and 24 h; however, there was additional effect with INDO + HS group. Furthermore, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO + HS. This suggests that there is an increase in morbidity risk with INDO + HS, likely resulting from significant gut injury.NEW & NOTEWORTHY This paper suggests that in a translational mouse model, NSAIDs may be counterindicated in situations that put an individual at risk of heat injury. We show here that a small, single dose of the NSAID indomethacin before heat stroke has a dramatic and highly damaging effect on the gut, which ultimately leads to increased systemic morbidity. PMID: 28596269 [PubMed - indexed for MEDLINE]

[Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency].

Fri, 11/05/2018 - 15:00
Related Articles [Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency]. Nan Fang Yi Ke Da Xue Xue Bao. 2016 Nov 20;36(11):1489-1495 Authors: Xiao Y, Jing Y, Chen JY, Li F, Cheng JR, Bi JL, Luo R, Zhao XS Abstract OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. RESULTS: Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate were increased in the plasma of yang-deficient subjects after lifestyle intervention. GFDHW treatment with lifestyle intervention significantly increased the concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol. CONCLUSION: GFDHW treatment improves yang deficiency possibly by increasing the concentrations of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol and promoting energy metabolism of the body. PMID: 27881338 [PubMed - indexed for MEDLINE]

metabolomics; +18 new citations

Thu, 10/05/2018 - 14:42
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 2018/05/10PubMed 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.

Epoxide Value-A Novel Marker for the Quality Assessment of Food Lipids.

Wed, 09/05/2018 - 14:15
Related Articles Epoxide Value-A Novel Marker for the Quality Assessment of Food Lipids. J Agric Food Chem. 2018 May 08;: Authors: Grüneis V, Pignitter M PMID: 29738241 [PubMed - as supplied by publisher]

Lipidomics reveal Aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate(ANIT)-induced intrahepatic cholestasis.

Wed, 09/05/2018 - 14:15
Related Articles Lipidomics reveal Aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate(ANIT)-induced intrahepatic cholestasis. Xenobiotica. 2018 May 08;:1-33 Authors: Wang BL, Zhang CW, Wang L, Tang KL, Tanaka N, Gonzalez FJ, Xu Y, Fang ZZ Abstract 1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employ to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine, and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1). 3. Knockout of Aryl hydrocarbon receptor (Ahr) in mice can significantly reverse alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor (Ahr) knockout significantly reversed alpha-naphthyl isothiocyanate (ANIT)-induced lipid metabolism alteration through regulating the expression of Chka. 4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice. PMID: 29737914 [PubMed - as supplied by publisher]

Metabolomics research on potential role for 9-cis-Retinoic acid in breast cancer progression.

Wed, 09/05/2018 - 14:15
Related Articles Metabolomics research on potential role for 9-cis-Retinoic acid in breast cancer progression. Cancer Sci. 2018 May 08;: Authors: Wu J, Yang R, Zhang L, Li Y, Liu B, Kang H, Fan Z, Tian Y, Liu S, Li T Abstract Deciphering the molecular networks that discriminate organ-confined breast cancer from metastatic breast cancer may lead to the identification of critical biomarkers for breast cancer invasion and aggressiveness. Here metabolomics, a global study of metabolites, has been applied to explore the metabolic alterations that characterize breast cancer progression. We profiled a total of 693 metabolites across 87 serum samples related to breast cancer (46 clinically localized and 41 metastatic breast cancer) and 49 normal samples. These unbiased metabolomic profiles were able to distinguish normal individuals, clinically localized and metastatic breast cancer patients. 9-cis-Retinoic acid, an isomer of all-trans retinoic acid, was identified as a differential metabolite that significantly decreased during breast cancer progression to metastasis, and its levels were also reduced in urine samples from biopsy positive breast cancer patients relative to biopsy negative individuals and in invasive breast cancer cells relative to benign MCF-10A cells. The addition of exogenous 9-cis-Retinoic acid to MDA-MB-231 cells and knock-down of aldehyde dehydrogenase 1 family member A1, an regulatory enzyme for 9-cis-Retinoic acid, remarkably impaired cell invasion and migration, presumably through preventing the key regulator cofilin from activation and inhibiting MMP2 and MMP9 expression. Taken together, our study revealed the potential inhibitory role for 9-cis-Retinoic acid in breast cancer progression by attenuating cell invasion and migration. This article is protected by copyright. All rights reserved. PMID: 29737597 [PubMed - as supplied by publisher]

metabolomics; +37 new citations

Tue, 08/05/2018 - 22:42
37 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 2018/05/08PubMed 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.

Metabolomics and Isotope Tracing.

Mon, 07/05/2018 - 22:26
Related Articles Metabolomics and Isotope Tracing. Cell. 2018 May 03;173(4):822-837 Authors: Jang C, Chen L, Rabinowitz JD Abstract Great strides have been made over the past decade toward comprehensive study of metabolism. Mass spectrometry (MS) has played a central role by enabling measurement of many metabolites simultaneously. Tracking metabolite labeling from stable isotope tracers can in addition reveal pathway activities. Here, we describe the basics of metabolite measurement by MS, including sample preparation, metabolomic analysis, and data interpretation. In addition, drawing on examples of successful experiments, we highlight the ways in which metabolomics and isotope tracing can illuminate biology. PMID: 29727671 [PubMed - in process]

TD/GC-MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum.

Mon, 07/05/2018 - 22:26
Related Articles TD/GC-MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum. Metabolomics. 2018;14(5):66 Authors: Lawal O, Knobel H, Weda H, Nijsen TME, Goodacre R, Fowler SJ, BreathDx consortium Abstract Introduction: Infections such as ventilator-associated pneumonia (VAP) can be caused by one or more pathogens. Current methods for identifying these pathogenic microbes often require invasive sampling, and can be time consuming, due to the requirement for prolonged cultural enrichment along with selective and differential plating steps. This results in delays in diagnosis which in such critically ill patients can have potentially life-threatening consequences. Therefore, a non-invasive and timely diagnostic method is required. Detection of microbial volatile organic compounds (VOCs) in exhaled breath is proposed as an alternative method for identifying these pathogens and may distinguish between mono- and poly-microbial infections. Objectives: To investigate volatile metabolites that discriminate between bacterial mono- and co-cultures. Methods: VAP-associated pathogens Enterobacter cloacae and Pseudomonas aeruginosa were cultured individually and together in artificial sputum medium for 24 h and their headspace was analysed for potential discriminatory VOCs by thermal desorption gas chromatography-mass spectrometry. Results: Of the 70 VOCs putatively identified, 23 were found to significantly increase during bacterial culture (i.e. likely to be released during metabolism) and 13 decreased (i.e. likely consumed during metabolism). The other VOCs showed no transformation (similar concentrations observed as in the medium). Bacteria-specific VOCs including 2-methyl-1-propanol, 2-phenylethanol, and 3-methyl-1-butanol were observed in the headspace of axenic cultures of E. cloacae, and methyl 2-ethylhexanoate in the headspace of P. aeruginosa cultures which is novel to this investigation. Previously reported VOCs 1-undecene and pyrrole were also detected. The metabolites 2-methylbutyl acetate and methyl 2-methylbutyrate, which are reported to exhibit antimicrobial activity, were elevated in co-culture only. Conclusion: The observed VOCs were able to differentiate axenic and co-cultures. Validation of these markers in exhaled breath specimens could prove useful for timely pathogen identification and infection type diagnosis. PMID: 29725275 [PubMed]

Metabolomics Research in Chronic Kidney Disease.

Mon, 07/05/2018 - 22:26
Related Articles Metabolomics Research in Chronic Kidney Disease. J Am Soc Nephrol. 2018 May 03;: Authors: Grams ME, Shafi T, Rhee EP PMID: 29724883 [PubMed - as supplied by publisher]

Empowering thyroid hormone research in human subjects using OMICs-technologies.

Mon, 07/05/2018 - 22:26
Related Articles Empowering thyroid hormone research in human subjects using OMICs-technologies. J Endocrinol. 2018 May 03;: Authors: Pietzner M, Kacprowski T, Friedrich N Abstract OMICs subsume different physiological layers including the genome, transcriptome, proteome, and metabolome. Recent advances in analytical techniques allow for the exhaustive determination of bio-molecules in all OMICs levels from less invasive human specimens such as blood and urine. Investigating OMICs in deeply characterized population-based or experimental studies has led to seminal improvement of our understanding of genetic determinants of thyroid function, identified putative thyroid hormone target genes and thyroid hormone-induced shifts in the plasma protein and metabolite content. Consequently, plasma bio-molecules have been suggested as surrogates of tissue-specific action of thyroid hormones. This review provides a brief introduction to OMICs in thyroid research with a particular focus on metabolomics studies in humans elucidating the important role of thyroid hormones for whole body metabolism in adults. PMID: 29724864 [PubMed - as supplied by publisher]

Validation of a plasma metabolomics model that allows anticipation of the occurrence of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients.

Mon, 07/05/2018 - 22:26
Related Articles Validation of a plasma metabolomics model that allows anticipation of the occurrence of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients. J Med Microbiol. 2018 May 04;: Authors: Monleón D, Talaya A, Giménez E, Vinuesa V, Morales JM, Hernández-Boluda JC, Pérez A, Piñana JL, Solano C, Navarro D Abstract A plasma metabolomic model obtained by means of untargeted 1H nuclear magnetic resonance, to which taurine, choline, methylamine, total glutathione, trimethylamine N-oxide, lactate, lysine, isoleucine, total fatty acids and unsaturated fatty acids contributed, was validated for the prediction of first episodes of cytomegalovirus (CMV) DNAaemia in a cohort of 79 allogeneic stem haematopoietic stem cell transplant (allo-HSCT) recipients. The predictive success rate was nearly 65 % for patients at both low and high risk of CMV-related complications according to their baseline characteristics. Plasma metabolomics profiling shortly after engraftment (day 21 after transplantation) allowed the anticipation of the occurrence of CMV DNAaemia in 71 % of patients. Plasma metabolomics analyses may be ancillary for identifying allo-HSCT patients at the highest risk of CMV DNAaemia who may benefit from early targeted antiviral prophylaxis. PMID: 29724268 [PubMed - as supplied by publisher]

Cigarette Smoking and the Pathogenesis of Systemic Lupus Erythematosus.

Mon, 07/05/2018 - 22:26
Related Articles Cigarette Smoking and the Pathogenesis of Systemic Lupus Erythematosus. Expert Rev Clin Immunol. 2018 May 03;: Authors: Speyer CB, Costenbader KH Abstract INTRODUCTION: Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures "trigger" or accelerate the disease in genetically-predisposed individuals. Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE- specific autoantibodies. Research has begun to search for possible explanations for the temporal nature of the relationship between current smoking and autoantibody positive-SLE. Here we review potential biologic mechanisms linking smoking and SLE risk, including effects upon T and B cells, inflammatory cytokines, oxidative stress, and the formation of short-lived DNA adducts. Expert Commentary: The directions for future research in this field include studies of gene-environment interactions, epigenetics, metabolomics and putative biologic mechanisms. PMID: 29724134 [PubMed - as supplied by publisher]

Unraveling Nutritional Regulation of Tacrolimus Biosynthesis in Streptomyces tsukubaensis through omic Approaches.

Mon, 07/05/2018 - 22:26
Related Articles Unraveling Nutritional Regulation of Tacrolimus Biosynthesis in Streptomyces tsukubaensis through omic Approaches. Antibiotics (Basel). 2018 May 01;7(2): Authors: Ordóñez-Robles M, Santos-Beneit F, Martín JF Abstract Streptomyces tsukubaensis stands out among actinomycetes by its ability to produce the immunosuppressant tacrolimus. Discovered about 30 years ago, this macrolide is widely used as immunosuppressant in current clinics. Other potential applications for the treatment of cancer and as neuroprotective agent have been proposed in the last years. In this review we introduce the discovery of S. tsukubaensis and tacrolimus, its biosynthetic pathway and gene cluster (fkb) regulation. We have focused this work on the omic studies performed in this species in order to understand tacrolimus production. Transcriptomics, proteomics and metabolomics have improved our knowledge about the fkb transcriptional regulation and have given important clues about nutritional regulation of tacrolimus production that can be applied to improve production yields. Finally, we address some points of S. tsukubaensis biology that deserve more attention. PMID: 29724001 [PubMed]

Improved phosphometabolome profiling applying isotope dilution strategy and capillary ion chromatography-tandem mass spectrometry.

Mon, 07/05/2018 - 22:26
Related Articles Improved phosphometabolome profiling applying isotope dilution strategy and capillary ion chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 15;1083:278-283 Authors: Stafsnes MH, Røst LM, Bruheim P Abstract The phosphometabolome is comprised of all phosphorylated metabolites including the major metabolite classes sugar phosphates and nucleoside phosphates. Phosphometabolites are invaluable in any cell as a part of primary- and energy- metabolism, and as building blocks in the biosynthesis of macromolecules. Here, we report quantitative profiling of the phosphometabolome by applying capillary ion chromatography-tandem mass spectrometry (capIC-MS/MS), ensuring improved chromatographic separation, robustness and quantitative precision. Baseline separation was achieved for six out of eight tested hexose phosphates. Quantitative precision and reproducibility was improved by introducing a fully uniformly (U) 13C-labeled biological extract and applying an isotope dilution (ID) correction strategy. A 13C-labeled biological extract does in principle contain internal standards (IS) for all metabolites, but low abundant metabolites pose a challenge, and solutions to this are discussed. The extreme reproducibility and reliability of this capIC-MS/MS method was demonstrated by running the instrumentation continuously for ten days. PMID: 29571119 [PubMed - indexed for MEDLINE]

Development and validation of an ultra high performance liquid chromatography-electrospray tandem mass spectrometry method using selective derivatisation, for the quantification of two reactive aldehydes produced by lipid peroxidation, HNE (4-hydroxy-2...

Mon, 07/05/2018 - 22:26
Related Articles Development and validation of an ultra high performance liquid chromatography-electrospray tandem mass spectrometry method using selective derivatisation, for the quantification of two reactive aldehydes produced by lipid peroxidation, HNE (4-hydroxy-2(E)-nonenal) and HHE (4-hydroxy-2(E)-hexenal) in faecal water. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 15;1083:171-179 Authors: Chevolleau S, Noguer-Meireles MH, Jouanin I, Naud N, Pierre F, Gueraud F, Debrauwer L Abstract Red or processed meat rich diets have been shown to be associated with an elevated risk of colorectal cancer (CRC). One major hypothesis involves dietary heme iron which induces lipid peroxidation. The quantification of the resulting reactive aldehydes (e.g. HNE and HHE) in the colon lumen is therefore of great concern since these compounds are known for their cytotoxic and genotoxic properties. UHPLC-ESI-MS/MS method has been developed and validated for HNE and HHE quantification in rat faeces. Samples were derivatised using a brominated reagent (BBHA) in presence of pre-synthesized deuterated internal standards (HNE-d11/HHE-d5), extracted by solid phase extraction, and then analysed by LC-positive ESI-MS/MS (MRM) on a TSQ Vantage mass spectrometer. The use of BBHA allowed the efficient stabilisation of the unstable and reactive hydroxy-alkenals HNE and HHE. The MRM method allowed selective detection of HNE and HHE on the basis of characteristic transitions monitored from both the 79 and 81 bromine isotopic peaks. This method was validated according to the European Medicines Agency (EMEA) guidelines, by determining selectivity, sensitivity, linearity, carry-over effect, recovery, matrix effect, repeatability, trueness and intermediate precision. The performance of the method enabled the quantification of HNE and HHE in concentrations 0.10-0.15 μM in faecal water. Results are presented on the application to the quantification of HNE and HHE in different faecal waters obtained from faeces of rats fed diets with various fatty acid compositions thus corresponding to different pro-oxidative features. PMID: 29549740 [PubMed - indexed for MEDLINE]

metabolomics; +26 new citations

Fri, 04/05/2018 - 14:57
26 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 2018/05/04PubMed 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.

metabolomics; +19 new citations

Thu, 03/05/2018 - 14:20
19 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 2018/05/03PubMed 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.

metabolomics; +23 new citations

Wed, 02/05/2018 - 13:52
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 2018/05/02PubMed 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.

metabolomics; +29 new citations

Tue, 01/05/2018 - 19:29
29 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 2018/05/01PubMed 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.

Pages