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

Exhaled breath condensate to discriminate individuals with different smoking habits by GC-TOF/MS.

Fri, 05/05/2017 - 14:27
Related Articles Exhaled breath condensate to discriminate individuals with different smoking habits by GC-TOF/MS. Sci Rep. 2017 May 03;7(1):1421 Authors: Peralbo-Molina A, Calderón-Santiago M, Jurado-Gámez B, Luque de Castro MD, Priego-Capote F Abstract Smoking is a crucial factor in respiratory diseases and lung inflammation, which are the reasons for high mortality worldwide. Despite the negative impact that tobacco consumption causes on health, few metabolomics studies have compared the composition of biofluids from smoker and non-smoker individuals. Exhaled breath condensate (EBC) is one of the biofluids less employed for clinical studies despite its non-invasive sampling and the foreseeable relationship between its composition and respiratory diseases. EBC was used in this research as clinical sample to compare three groups of individuals: current smokers (CS), former smokers (FS) and never smokers (NS). Special attention was paid to the cumulative consumption expressed as smoked pack-year. The levels of 12 metabolites found statistically significant among the three groups of individuals were discussed to find an explanation to their altered levels. Significant compounds included monoacylglycerol derivatives, terpenes and other compounds, the presence of which could be associated to the influence of smoking on the qualitative and quantitative composition of the microbiome. PMID: 28469199 [PubMed - in process]

Simultaneous Quantification of Amino Metabolites in Multiple Metabolic Pathways Using Ultra-High Performance Liquid Chromatography with Tandem-mass Spectrometry.

Fri, 05/05/2017 - 14:27
Related Articles Simultaneous Quantification of Amino Metabolites in Multiple Metabolic Pathways Using Ultra-High Performance Liquid Chromatography with Tandem-mass Spectrometry. Sci Rep. 2017 May 03;7(1):1423 Authors: Wang J, Zhou L, Lei H, Hao F, Liu X, Wang Y, Tang H Abstract Metabolites containing amino groups cover multiple pathways and play important roles in redox homeostasis and biosyntheses of proteins, nucleotides and neurotransmitters. Here, we report a new method for simultaneous quantification of 124 such metabolites. This is achieved by derivatization-assisted sensitivity enhancement with 5-aminoisoquinolyl-N-hydroxysuccinimidyl carbamate (5-AIQC) followed with comprehensive analysis using ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry (UHPLC-MS/MS). In an one-pot manner, this quantification method enables simultaneous coverage of 20 important metabolic pathways including protein biosynthesis/degradation, biosyntheses of catecholamines, arginine and glutathione, metabolisms of homocysteine, taurine-hypotaurine etc. Compared with the reported ones, this method is capable of simultaneously quantifying thiols, disulfides and other oxidation-prone analytes in a single run and suitable for quantifying aromatic amino metabolites. This method is also much more sensitive for all tested metabolites with LODs well below 50 fmol (at sub-fmol for most tested analytes) and shows good precision for retention time and quantitation with inter-day and intra-day relative standard deviations (RSDs) below 15% and good recovery from renal cancer tissue, rat urine and plasma. The method was further applied to quantify the amino metabolites in silkworm hemolymph from multiple developmental stages showing its applicability in metabolomics and perhaps some clinical chemistry studies. PMID: 28469184 [PubMed - in process]

Serum Metabolomics Investigation of Humanized Mouse Model with Dengue Infection.

Fri, 05/05/2017 - 14:27
Related Articles Serum Metabolomics Investigation of Humanized Mouse Model with Dengue Infection. J Virol. 2017 May 03;: Authors: Cui L, Hou J, Fang J, Lee YH, Costa VV, Wong LH, Chen Q, Ooi EE, Tannenbaum SR, Chen J, Ong CN Abstract Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted a mass spectrometry-based serum metabolic profiling from a humanized mice (humice) model with DENV serotype 2 infection at 0, 3, 7, 14 and 28 days post infection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acid and derivatives, free fatty acids, bile acid, etc. These metabolites showed a reversible change trend - most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that these metabolites might serve as prognostic markers of the disease in humice. Major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, bile acid biosynthesis, etc. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses between humice and human to DENV infections and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.Importance: Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. As yet, there is currently no effective treatment against the disease, and the lack of an appropriate small-animal model of dengue infection has greatly increased the challenges in the study of dengue pathogenesis and the development of therapeutics. Metabolomics provides global views of small molecule metabolites and is a useful tool of finding metabolic pathways related to disease processes. Here we conducted serum metabolomics study on a humanized mice model, which has significant levels of human platelets, monocytes/macrophages, and hepatocytes, with dengue infection. Forty-eight differential metabolites were identified, and the underlying perturbed metabolic pathways are quite similar to the pathways altered in dengue patients in previous metabolomics studies, indicating that humanized mice could be a highly relevant small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. PMID: 28468882 [PubMed - as supplied by publisher]

Proceedings of 3(rd) Australian Lipid Meeting.

Fri, 05/05/2017 - 14:27
Related Articles Proceedings of 3(rd) Australian Lipid Meeting. Metabolites. 2017 May 01;7(2): Authors: Brown SH, Rupasinghe TWT Abstract n/a. PMID: 28468309 [PubMed - in process]

The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease.

Fri, 05/05/2017 - 14:27
Related Articles The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease. Am J Hum Genet. 2017 Feb 02;100(2):185-192 Authors: Ramoni RB, Mulvihill JJ, Adams DR, Allard P, Ashley EA, Bernstein JA, Gahl WA, Hamid R, Loscalzo J, McCray AT, Shashi V, Tifft CJ, Undiagnosed Diseases Network, Wise AL Abstract Diagnosis at the edges of our knowledge calls upon clinicians to be data driven, cross-disciplinary, and collaborative in unprecedented ways. Exact disease recognition, an element of the concept of precision in medicine, requires new infrastructure that spans geography, institutional boundaries, and the divide between clinical care and research. The National Institutes of Health (NIH) Common Fund supports the Undiagnosed Diseases Network (UDN) as an exemplar of this model of precise diagnosis. Its goals are to forge a strategy to accelerate the diagnosis of rare or previously unrecognized diseases, to improve recommendations for clinical management, and to advance research, especially into disease mechanisms. The network will achieve these objectives by evaluating patients with undiagnosed diseases, fostering a breadth of expert collaborations, determining best practices for translating the strategy into medical centers nationwide, and sharing findings, data, specimens, and approaches with the scientific and medical communities. Building the UDN has already brought insights to human and medical geneticists. The initial focus has been on data sharing, establishing common protocols for institutional review boards and data sharing, creating protocols for referring and evaluating patients, and providing DNA sequencing, metabolomic analysis, and functional studies in model organisms. By extending this precision diagnostic model nationally, we strive to meld clinical and research objectives, improve patient outcomes, and contribute to medical science. PMID: 28157539 [PubMed - indexed for MEDLINE]

Analyzing and interpreting genome data at the network level with ConsensusPathDB.

Fri, 05/05/2017 - 14:27
Related Articles Analyzing and interpreting genome data at the network level with ConsensusPathDB. Nat Protoc. 2016 Oct;11(10):1889-907 Authors: Herwig R, Hardt C, Lienhard M, Kamburov A Abstract ConsensusPathDB consists of a comprehensive collection of human (as well as mouse and yeast) molecular interaction data integrated from 32 different public repositories and a web interface featuring a set of computational methods and visualization tools to explore these data. This protocol describes the use of ConsensusPathDB (http://consensuspathdb.org) with respect to the functional and network-based characterization of biomolecules (genes, proteins and metabolites) that are submitted to the system either as a priority list or together with associated experimental data such as RNA-seq. The tool reports interaction network modules, biochemical pathways and functional information that are significantly enriched by the user's input, applying computational methods for statistical over-representation, enrichment and graph analysis. The results of this protocol can be observed within a few minutes, even with genome-wide data. The resulting network associations can be used to interpret high-throughput data mechanistically, to characterize and prioritize biomarkers, to integrate different omics levels, to design follow-up functional assay experiments and to generate topology for kinetic models at different scales. PMID: 27606777 [PubMed - indexed for MEDLINE]

metabolomics; +21 new citations

Thu, 04/05/2017 - 13:52
21 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 2017/05/04PubMed 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.

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischemic heart?

Tue, 02/05/2017 - 13:12
Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischemic heart? Cardiovasc Res. 2017 Apr 29;: Authors: Perrino C, Barabási AL, Condorelli G, Davidson SM, De Windt L, Dimmeler S, Engel FB, Hausenloy DJ, Hill JA, Van Laake LW, Lecour S, Leor J, Madonna R, Mayr M, Prunier F, Sluijter JP, Schulz R, Thum T, Ytrehus K, Ferdinandy P Abstract Despite advances in myocardial reperfusion therapies, acute myocardial ischemia/reperfusion injury and consequent ischemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signaling networks activated in the ischemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischemia, putting it in the context of the human "diseasome".Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischemia/reperfusion injury and ischemic heart failure in the post-genomic era. PMID: 28460026 [PubMed - as supplied by publisher]

Metabolomics reveals intratumor heterogeneity - Implications for precision medicine.

Tue, 02/05/2017 - 13:12
Related Articles Metabolomics reveals intratumor heterogeneity - Implications for precision medicine. EBioMedicine. 2017 Apr 24;: Authors: Liu X, Locasale JW PMID: 28457617 [PubMed - as supplied by publisher]

Changes in hepatic TRβ protein expression, lipogenic gene expression, and long chain acylcarnitine levels during chronic hyperthyroidism and T3 withdrawal in a mouse model.

Tue, 02/05/2017 - 13:12
Related Articles Changes in hepatic TRβ protein expression, lipogenic gene expression, and long chain acylcarnitine levels during chronic hyperthyroidism and T3 withdrawal in a mouse model. Thyroid. 2017 Apr 29;: Authors: Ohba K, Sinha RA, Leow MK, Iannucci LF, Singh BK, Zhou J, Kovalik JP, Liao XH, Refetoff S, Sng JCG, Yen PM Abstract BACKGROUND: Thyroid hormone (TH) has important roles in regulating hepatic metabolism. We previously reported that most hepatic genes activated by a single T3 injection became desensitized after multiple injections, and that approximately 10% of target genes did not return to basal expression levels after T3 withdrawal despite normalization of serum TH and TSH levels. To determine the possible mechanism(s) for desensitization and incomplete recovery of hepatic target gene transcription and their effects on metabolism, we measured mRNA and/or protein expression levels of key regulators of TH action as well as metabolomic changes after chronic T3 treatment and withdrawal. METHODS: Adult male mice were treated with daily injections of T3 (20 μg per100 g body weight) for 14 days followed by the cessation of T3 for 10 days. Livers were harvested at 6 hours, 24 hours, and 14 days after the first T3 injection, and 10 days after withdrawal, and then analyzed by qRT-PCR, Western blotting, and metabolomics. RESULTS: Although TH receptor (TRα and TRβ) mRNAs decreased slightly after chronic T3 treatment, only TRβ protein decreased before returning to basal expression level after withdrawal. Expression of other regulators of TH action was unchanged. TRβ protein expression also was decreased in adult male monocarboxylate transporter-8 (Mct8)-knockout mice, an in vivo model of chronic intrahepatic hyperthyroidism. Previously, we found increased hepatic long-chain acylcarnitines (LCACs) after acute TH treatment; however, in this study, LCACs were unchanged after chronic T3, and paradoxically increased after T3 withdrawal. Pathway analyses of our previous microarray results showed up-regulation of lipogenic genes after acute T3 treatment and withdrawal. Phosphorylation of acetyl-CoA carboxylase also decreased after T3 withdrawal. CONCLUSIONS: Decreased hepatic TRβ protein expression occurred after chronic T3 exposure in adult male wild-type and Mct8-knockout mice. Gene array pathway and metabolomics analyses showed abnormalities in hepatic lipogenic gene expression and acylcarnitine levels, respectively, after withdrawal despite normalization of serum TSH and TH levels. These findings may help explain the variable clinical presentations of some patients during hyperthyroidism and recovery, since TRβ protein, target gene expression, and metabolic adaptive changes can occur in individual tissues without necessarily being reflected by circulating TH and TSH concentrations. PMID: 28457184 [PubMed - as supplied by publisher]

Ionomic and physiological responses to low nitrogen stress in Tibetan wild and cultivated barley.

Tue, 02/05/2017 - 13:12
Related Articles Ionomic and physiological responses to low nitrogen stress in Tibetan wild and cultivated barley. Plant Physiol Biochem. 2017 Feb;111:257-265 Authors: Quan X, Zeng J, Han Z, Zhang G Abstract In a previous study, we identified the low-nitrogen (LN) tolerant accessions from the Tibetan wild barley (Hordeum vulgare subsp. spontaneum). In this study, two wild barley genotypes (XZ149, LN-tolerant and XZ56, LN-sensitive) and a barley cultivar ZD9 (H. vulgare) were used to determine the LN tolerant mechanism underlying the wild barley in the ionomic and physiological aspects. XZ149 exhibited higher LN tolerance with highest relative dry weight and N accumulation among three barley genotypes under LN stress. When exposed to LN stress, XZ149 had more N transportation from roots to leaves, and remained relatively higher activities of nitrate reductase (NR, EC.1.7.1.1) and glutamine synthetase (GS, EC.6.3.1.2) in leaves than other two genotypes, ensuring its higher capacity of N assimilation and utilization. The ionome analysis showed that LN stress had a significant effect on tissue ionome and the effect was genotypic and tissue-specific difference. On the whole, XZ149 maintained more stable Mn and Cu contents in roots, and less reduction of root P, K and Ca contents than XZ56 and ZD9 when exposed to LN stress. It may be assumed that more N movement into shoots, greater N assimilating capacity and specific rearrangement of nutrient element levels in tissues under LN stress are attributed to LN tolerance in XZ149. PMID: 27951495 [PubMed - indexed for MEDLINE]

Experimental Evolution of Metabolic Dependency in Bacteria.

Tue, 02/05/2017 - 13:12
Related Articles Experimental Evolution of Metabolic Dependency in Bacteria. PLoS Genet. 2016 Nov;12(11):e1006364 Authors: D'Souza G, Kost C Abstract Bacteria frequently lose biosynthetic genes, thus making them dependent on an environmental uptake of the corresponding metabolite. Despite the ubiquity of this 'genome streamlining', it is generally unclear whether the concomitant loss of biosynthetic functions is favored by natural selection or rather caused by random genetic drift. Here we demonstrate experimentally that a loss of metabolic functions is strongly selected for when the corresponding metabolites can be derived from the environment. Serially propagating replicate populations of the bacterium Escherichia coli in amino acid-containing environments revealed that auxotrophic genotypes rapidly evolved in less than 2,000 generations in almost all replicate populations. Moreover, auxotrophs also evolved in environments lacking amino acids-yet to a much lesser extent. Loss of these biosynthetic functions was due to mutations in both structural and regulatory genes. In competition experiments performed in the presence of amino acids, auxotrophic mutants gained a significant fitness advantage over the evolutionary ancestor, suggesting their emergence was selectively favored. Interestingly, auxotrophic mutants derived amino acids not only via an environmental uptake, but also by cross-feeding from coexisting strains. Our results show that adaptive fitness benefits can favor biosynthetic loss-of-function mutants and drive the establishment of intricate metabolic interactions within microbial communities. PMID: 27814362 [PubMed - indexed for MEDLINE]

Functional and cellular consequences of covalent target protein modification by furan in rat liver.

Tue, 02/05/2017 - 13:12
Related Articles Functional and cellular consequences of covalent target protein modification by furan in rat liver. Toxicology. 2016 Jun 15;361-362:49-61 Authors: Ramm S, Limbeck E, Mally A Abstract Furan hepatotoxicity is thought to be linked to covalent binding of its reactive metabolite, cis-2-butene-1,4-dial, to hepatic proteins critical for cell homeostasis and survival. We previously identified 61 putative furan target proteins, which participate in various cellular processes including carbohydrate metabolism, fatty acid β-oxidation, adenosine triphosphate (ATP) synthesis, protein folding and maintenance of redox homeostasis. To further investigate the biological significance of target protein modification, this study was designed to determine the impact of furan on the activity of key target enzymes involved in glycolysis, β-oxidation, ATP synthesis, and redox regulation in rat liver, and to link these functional changes to alterations in cellular processes. While cis-2-butene-1,4-dial inhibited thioredoxin 1 (Txn1) in a cell-free assay, in livers of rats treated with a single high dose of furan Txn1 activity was markedly increased due to rapid up-regulation of Txn1 mRNA expression. Significant inhibition of glyceraldehyde-3-phosphate dehydrogenase and metabolic changes consistent with blocked glycolytic breakdown of glucose were observed in rat liver in response to a single high dose of furan. In contrast, furan treatment resulted in increased activity of enoyl-CoA hydratase and enhanced production of ketone bodies, indicative of increased utilization of fatty acids as energy source. Consistent with changes in TCA cycle metabolites, furan treatment resulted in a reduction of succinate dehydrogenase activity, supporting mitochondrial dysfunction as a critical event in furan toxicity. No significant changes in target protein function were observed following repeated administration of furan at lower dose (0.1 and 0.5mg/kg bw for 4 weeks) closer to estimated human exposure to furan via food. Although the relative contribution of furan mediated alterations in metabolic pathways and antioxidant defense to the overall toxic response to furan, including considerations of dose and time, remains to be established, our work contributes to mapping biological processes and toxicity pathways modulated by reactive electrophiles. PMID: 27402187 [PubMed - indexed for MEDLINE]

Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

Mon, 01/05/2017 - 12:44
Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism. Pharmacol Res. 2017 Apr 26;: Authors: Qu C, Yuan ZW, Yu XT, Huang YF, Yang GH, Chen JN, Lai XP, Su ZR, Zeng HF, Xie Y, Zhang XJ Abstract Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC. PMID: 28456683 [PubMed - as supplied by publisher]

Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

Mon, 01/05/2017 - 12:44
Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease. Arch Biochem Biophys. 2017 Apr 26;: Authors: Nababan S, Nishiumi S, Kawano Y, Kobayashi T, Yoshida M, Azuma T Abstract BACKGROUND: This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. RESULTS: The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend: <0.001). CONCLUSION: Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. PMID: 28456640 [PubMed - as supplied by publisher]

Corrigendum to "Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration" [Metabolism vol. 70, May 2017, pages 31-41].

Mon, 01/05/2017 - 12:44
Corrigendum to "Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration" [Metabolism vol. 70, May 2017, pages 31-41]. Metabolism. 2017 Apr 26;: Authors: Alvarez JA, Chong EY, Walker DI, Chandler JD, Michalski ES, Grossmann RE, Uppal K, Li S, Frediani JK, Tirouvanziam R, Tran VT, Tangpricha V, Jones DP, Ziegler TR PMID: 28456337 [PubMed - as supplied by publisher]

Using precursor ion scan of 184 with liquid chromatography-electrospray ionization-tandem mass spectrometry for concentration normalization in cellular lipidomic studies.

Mon, 01/05/2017 - 12:44
Using precursor ion scan of 184 with liquid chromatography-electrospray ionization-tandem mass spectrometry for concentration normalization in cellular lipidomic studies. Anal Chim Acta. 2017 Jun 08;971:68-77 Authors: Chao HC, Chen GY, Hsu LC, Liao HW, Yang SY, Wang SY, Li YL, Tang SC, Tseng YJ, Kuo CH Abstract Cellular lipidomic studies have been favored approaches in many biomedical research areas. To provide fair comparisons of the studied cells, it is essential to perform normalization of the determined concentration before lipidomic analysis. This study proposed a cellular lipidomic normalization method by measuring the phosphatidylcholine (PC) and sphingomyelin (SM) contents in cell extracts. To provide efficient analysis of PC and SM in cell extracts, flow injection analysis-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS) with a precursor ion scan (PIS) of m/z 184 was used, and the parameters affecting the performance of the method were optimized. Good linearity could be observed between the cell extract dilution factor and the reciprocal of the total ion chromatogram (TIC) area in the PIS of m/z 184 within the dilution range of 1- to 16-fold (R(2) = 0.998). The calibration curve could be used for concentration adjustment of the unknown concentration of a cell extract. The intraday and intermediate precisions were below 10%. The accuracy ranged from 93.0% to 105.6%. The performance of the new normalization method was evaluated using different numbers of HCT-116 cells. Sphingosine, ceramide (d18:1/18:0), SM (d18:1/18:0) and PC (16:1/18:0) were selected as the representative test lipid species, and the results showed that the peak areas of each lipid species obtained from different cell numbers were within a 20% variation after normalization. Finally, the PIS of 184 normalization method was applied to study ischemia-induced neuron injury using oxygen and glucose deprivation (OGD) on primary neuronal cultured cells. Our results showed that the PIS of 184 normalization method is an efficient and effective approach for concentration normalization in cellular lipidomic studies. PMID: 28456285 [PubMed - in process]

metabolomics; +30 new citations

Sun, 30/04/2017 - 12:11
30 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 2017/04/30PubMed 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.

Microbial use of low molecular weight DOM in filtered and unfiltered freshwater: Role of ultra-small microorganisms and implications for water quality monitoring.

Fri, 28/04/2017 - 14:27
Related Articles Microbial use of low molecular weight DOM in filtered and unfiltered freshwater: Role of ultra-small microorganisms and implications for water quality monitoring. Sci Total Environ. 2017 Apr 24;598:377-384 Authors: Brailsford FL, Glanville HC, Marshall MR, Golyshin PN, Johnes PJ, Yates CA, Owen AT, Jones DL Abstract Dissolved organic matter (DOM) plays a central role in regulating productivity and nutrient cycling in freshwaters. It is therefore vital that we can representatively sample and preserve DOM in freshwaters for subsequent analysis. Here we investigated the effect of filtration, temperature (5 and 25°C) and acidification (HCl) on the persistence of low molecular weight (MW) dissolved organic carbon (DOC), nitrogen (DON) and orthophosphate in oligotrophic and eutrophic freshwater environments. Our results showed the rapid loss of isotopically-labelled glucose and amino acids from both filtered (0.22 and 0.45μm) and unfiltered waters. We ascribe this substrate depletion in filtered samples to the activity of ultra-small (<0.45μm) microorganisms (bacteria and archaea) present in the water. As expected, the rate of C, N and P loss was much greater at higher temperatures and was repressed by the addition of HCl. Based on our results and an evaluation of the protocols used in recently published studies, we conclude that current techniques used to sample water for low MW DOM characterisation are frequently inadequate and lack proper validation. In contrast to the high degree of analytical precision and rigorous statistical analysis of most studies, we argue that insufficient consideration is still given to the presence of ultra-small microorganisms and potential changes that can occur in the low MW fraction of DOM prior to analysis. PMID: 28448929 [PubMed - as supplied by publisher]

Chemodiversity of two closely related tetraploid Centaurium species and their hexaploid hybrid: Metabolomic search for high-resolution taxonomic classifiers.

Fri, 28/04/2017 - 14:27
Related Articles Chemodiversity of two closely related tetraploid Centaurium species and their hexaploid hybrid: Metabolomic search for high-resolution taxonomic classifiers. Phytochemistry. 2017 Apr 24;140:27-44 Authors: Banjanac T, Dragićević M, Šiler B, Gašić U, Bohanec B, Nestorović Živković J, Trifunović S, Mišić D Abstract Species within the genus Centaurium readily hybridize and polyploid complexes are often seen in natural populations. We describe phytochemical profiles of newly discovered allohexaploid hybrid, here named Centaurium pannonicum, and its parental tetraploid species C. erythraea and rare C. littorale ssp. compressum. Our aim was to examine chemodiversity of these taxa in the area of Vojvodina (North Serbia) and to perform metabolomics search for chemical classifiers which would provide high resolution discrimination of parental and hybrid individuals. In sum, UHPLC-MS/MS Orbitrap metabolomics fingerprinting revealed seventy compounds in methanol extracts. Despite the lack of qualitative chemical novelty in hybrid plants, UHPLC-qqqMS targeted metabolomics approach, aimed at three secoiridoid compounds and seventeen phenolics, pointed to considerable differences in quantitative composition of these dominant compounds among the plant taxa studied. In addition to the difference in the ploidy levels, the hybrid taxon was well distinguished from both parental species based on metabolite profiles, and, for most individuals, positioned intermediately to the parental taxa in both PCA and hierarchical clustering. After optimizing and comparing several statistical learning methods, it was possible to narrow the number of taxonomic classifiers to five (three xanthones, one secoiridoid glycoside, and one phenolic acid), while increasing the differentiation resolution. The presented metabolomics approach will certainly, along with morphometrics and molecular genetics studies, have high impact on further elucidation of complex relationships among taxa within the genus Centaurium. PMID: 28448798 [PubMed - as supplied by publisher]

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