PubMed

Related Articles [Initial study on discrimination of oral microorganisms with the metabonomics technique]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2007 Aug;25(4):342-4 Authors: Li M, Xiao LY, Li JY, Kong XL, Yu JH, Zhou JL, Xiao XR, Zhu Z, Gong QM, Li W Abstract OBJECTIVE: To evaluate the feasibility of employing metabonomics method in identification of oral pathogenic bacteria. METHODS: The Streptococcus mutans ATCC25175 and Actinomyces viscosus ATCC15987 were respectively inoculated in same certain culture medium. The growth curves of the inoculated bacteria were drown by turbidimetry. The culture solutions in four different growth phases of the both bacteria were used to test with the 1H-Nuclear magnetic resonance (1H-NMR) spectroscopy respectively. The data of 1H-NMR spectroscopy results were analyzed by principal components analysis (PCA). RESULTS: The PCA showed the obvious clustering phenomena and the points of two group data stayed differentially together by two clusters. Therefore, the NMR-based metabonomics profiles can discriminate the two different kind of bacteria. CONCLUSION: The metabonomics can be expected to be a kind of promising useful method in quick discrimination of oral pathogenic bacteria. PMID: 17896487 [PubMed - indexed for MEDLINE]

Integrative Metabolic Signatures for Hepatic Radiation Injury. PLoS One. 2015;10(6):e0124795 Authors: Kurland IJ, Broin PÓ, Golden A, Su G, Meng F, Liu L, Mohney R, Kulkarni S, Guha C Abstract BACKGROUND: Radiation-induced liver disease (RILD) is a dose-limiting factor in curative radiation therapy (RT) for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice. METHODS: Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI) and were contrasted to mice, which received 10 Gy whole body irradiation (WBI). Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry. RESULTS: Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate), fatty acids (lineolate, n-hexadecanoic acid) and DNA damage markers (uridine). CONCLUSIONS : We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney. PMID: 26046990 [PubMed - as supplied by publisher]

A comprehensive quantification method for eicosanoids and related compounds by using liquid chromatography/mass spectrometry with high speed continuous ionization polarity switching. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 May 27;995-996C:74-84 Authors: Yamada M, Kita Y, Kohira T, Yoshida K, Hamano F, Tokuoka SM, Shimizu T Abstract Fatty acids and related metabolites, comprising several hundreds of molecular species, are an important target in disease metabolomics, as they are involved in various mammalian pathologies and physiologies. Selected reaction monitoring (SRM) analysis, which is capable of monitoring hundreds of compounds in a single run, has been widely used for comprehensive quantification. However, it is difficult to monitor a large number of compounds with different ionization polarity, as polarity switching requires a sub-second period per cycle in classical mass spectrometers. In the present study, we developed and evaluated a comprehensive quantification method for eicosanoids and related compounds by using LC/MS with high-speed continuous ionization polarity switching. The new method employs a fast (30ms/cycle) continuous ionization polarity switching, and differentiates 137 targets either by chromatography or by SRM transition. Polarity switching did not affect the lower limits of quantification, which ranged similarly from 0.5 to 200pg on column. Lipid extracts from mouse tissues were analyzed by this method, and 65 targets were quantitatively detected in the brain, including 6 compounds analyzed in the positive ion mode. We demonstrated that a fast continuous ionization polarity switching enables the quantification of a wide variety of lipid mediator species without compromising the sensitivity and reliability. PMID: 26046978 [PubMed - as supplied by publisher]

MUC16-mediated activation of mTOR and c-Myc reprograms pancreatic cancer metabolism. Oncotarget. 2015 Jun 3; Authors: Shukla SK, Gunda V, Abrego J, Haridas D, Mishra A, Souchek J, Chaika NV, Yu F, Sasson AR, Lazenby AJ, Batra SK, Singh PK Abstract MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global metabolic alterations in MUC16 knockdown pancreatic cancer cells, as compared to the controls. Specifically, glycolytic and nucleotide metabolite pools were significantly decreased. We observed similar metabolic alterations that correlated with MUC16 expression in primary tumor tissue specimens from human pancreatic adenocarcinoma cancer patients. Overall, our results demonstrate that MUC16 plays an important role in metabolic reprogramming of pancreatic cancer cells by increasing glycolysis and enhancing motility and invasiveness. PMID: 26046375 [PubMed - as supplied by publisher]

Related Articles The holy grail of cystic fibrosis research: pharmacological repair of the F508del-CFTR mutation. Ann Transl Med. 2015 May;3(Suppl 1):S24 Authors: Maiuri L, De Stefano D, Raia V, Kroemer G PMID: 26046070 [PubMed]

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 2015/06/05PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2015/06/04PubMed comprises more than 24 million 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.

Ecotoxicogenomic Approaches for Understanding Molecular Mechanisms of Environmental Chemical Toxicity Using Aquatic Invertebrate, Daphnia Model Organism. Int J Mol Sci. 2015;16(6):12261-12287 Authors: Kim HJ, Koedrith P, Seo YR Abstract Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term "ecotoxicogenomics" has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development's toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotypic outcomes linked to particular gene function(s) and mechanistic understanding of aquatic ecotoxicology as well as exploration of useful biomarkers. Furthermore, key challenges that currently face aquatic ecotoxicology (e.g., predicting toxicant responses among a broad spectrum of phytogenetic groups, predicting impact of temporal exposure on toxicant responses) necessitate the parallel use of other model organisms, both aquatic and terrestrial. By investigating gene expression profiling in an environmentally important organism, this provides viable support for the utility of ecotoxicogenomics. PMID: 26035755 [PubMed - as supplied by publisher]

Comparison of Fruits of Forsythia suspensa at Two Different Maturation Stages by NMR-Based Metabolomics. Molecules. 2015;20(6):10065-10081 Authors: Jia J, Zhang F, Li Z, Qin X, Zhang L Abstract Forsythiae Fructus (FF), the dried fruit of Forsythia suspensa, has been widely used as a heat-clearing and detoxifying herbal medicine in China. Green FF (GF) and ripe FF (RF) are fruits of Forsythia suspensa at different maturity stages collected about a month apart. FF undergoes a complex series of physical and biochemical changes during fruit ripening. However, the clinical uses of GF and RF have not been distinguished to date. In order to comprehensively compare the chemical compositions of GF and RF, NMR-based metabolomics coupled with HPLC and UV spectrophotometry methods were adopted in this study. Furthermore, the in vitro antioxidant and antibacterial activities of 50% methanol extracts of GF and RF were also evaluated. A total of 27 metabolites were identified based on NMR data, and eight of them were found to be different between the GF and RF groups. The GF group contained higher levels of forsythoside A, forsythoside C, cornoside, rutin, phillyrin and gallic acid and lower levels of rengyol and β-glucose compared with the RF group. The antioxidant activity of GF was higher than that of RF, but no significant difference was observed between the antibacterial activities of GF and RF. Given our results showing their distinct chemical compositions, we propose that NMR-based metabolic profiling can be used to discriminate between GF and RF. Differences in the chemical and biological activities of GF and RF, as well as their clinical efficacies in traditional Chinese medicine should be systematically investigated in future studies. PMID: 26035103 [PubMed - as supplied by publisher]

A 1H-NMR-Based Metabonomic Study on the Anti-Depressive Effect of the Total Alkaloid of Corydalis Rhizoma. Molecules. 2015;20(6):10047-10064 Authors: Wu H, Wang P, Liu M, Tang L, Fang J, Zhao Y, Zhang Y, Li D, Xu H, Yang H Abstract Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics. PMID: 26035102 [PubMed - as supplied by publisher]

Metabolomic Identification of a Novel Pathway of Blood Pressure Regulation Involving Hexadecanedioate. Hypertension. 2015 Jun 1; Authors: Menni C, Graham D, Kastenmüller G, Alharbi NH, Alsanos SM, McBride M, Mangino M, Titcombe P, Shin SY, Psatha M, Geisendorfer T, Huber A, Peters A, Wang-Sattler R, Xu T, Brosnan MJ, Trimmer J, Reichel C, Mohney RP, Soranzo N, Edwards MH, Cooper C, Church AC, Suhre K, Gieger C, Dominiczak AF, Spector TD, Padmanabhan S, Valdes AM Abstract High blood pressure is a major contributor to the global burden of disease and discovering novel causal pathways of blood pressure regulation has been challenging. We tested blood pressure associations with 280 fasting blood metabolites in 3980 TwinsUK females. Survival analysis for all-cause mortality was performed on significant independent metabolites (P<8.9 10(-5)). Replication was conducted in 2 independent cohorts KORA (n=1494) and Hertfordshire (n=1515). Three independent animal experiments were performed to establish causality: (1) blood pressure change after increasing circulating metabolite levels in Wistar-Kyoto rats; (2) circulating metabolite change after salt-induced blood pressure elevation in spontaneously hypertensive stroke-prone rats; and (3) mesenteric artery response to noradrenaline and carbachol in metabolite treated and control rats. Of the15 metabolites that showed an independent significant association with blood pressure, only hexadecanedioate, a dicarboxylic acid, showed concordant association with blood pressure (systolic BP [SBP]: β [95% confidence interval], 1.31 [0.83-1.78], P=6.81×10(-8); diastolic BP [DBP]: 0.81 [0.5-1.11], P=2.96×10(-7)) and mortality (hazard ratio [95% confidence interval], 1.49 [1.08-2.05]; P=0.02) in TwinsUK. The blood pressure association was replicated in KORA and Hertfordshire. In the animal experiments, we showed that oral hexadecanedioate increased both circulating hexadecanedioate and blood pressure in Wistar-Kyoto rats, whereas blood pressure elevation with oral sodium chloride in hypertensive rats did not affect hexadecanedioate levels. Vascular reactivity to noradrenaline was significantly increased in mesenteric resistance arteries from hexadecanedioate-treated rats compared with controls, indicated by the shift to the left of the concentration-response curve (P=0.013). Relaxation to carbachol did not show any difference. Our findings indicate that hexadecanedioate is causally associated with blood pressure regulation through a novel pathway that merits further investigation. PMID: 26034203 [PubMed - as supplied by publisher]

Identification and characterisation of citrullinated antigen-specific B cells in peripheral blood of patients with rheumatoid arthritis. Ann Rheum Dis. 2015 Jun 1; Authors: Kerkman PF, Fabre E, van der Voort EI, Zaldumbide A, Rombouts Y, Rispens T, Wolbink G, Hoeben RC, Spits H, Baeten DL, Huizinga TW, Toes RE, Scherer HU Abstract OBJECTIVES: Immunity to citrullinated antigens is a hallmark of rheumatoid arthritis (RA). We set out to elucidate its biology by identifying and characterising citrullinated antigen-specific B cells in peripheral blood of patients with RA. METHODS: Differentially labelled streptavidin and extravidin tetramers were conjugated to biotinylated CCP2 or control antigens and used in flow cytometry to identify citrullinated antigen-specific B cells in peripheral blood. Tetramer-positive and tetramer-negative B cells were isolated by fluorescence activated cell sorting (FACS) followed by in vitro culture and analysis of culture supernatants for the presence of antibodies against citrullinated protein antigens (ACPA) by ELISA. Cells were phenotypically characterised by flow cytometry. RESULTS: By combining differentially labelled CCP2 tetramers, we successfully separated citrullinated antigen-specific B cells from non-specific background signals. Isolated tetramer-positive B cells, but not tetramer-negative cells, produced large amounts of ACPA upon in vitro stimulation. Phenotypic analyses revealed that citrullinated antigen-specific B cells displayed markers of class-switched memory B cells and plasmablasts, whereas only few cells displayed a naïve phenotype. The frequency of tetramer-positive cells was high (up to 1/500 memory B cells with a median of 1/12 500 total B cells) and correlated with ACPA serum titres and spontaneous ACPA production in culture. CONCLUSIONS: We developed a technology to identify and isolate citrullinated antigen-specific B cells from peripheral blood of patients with RA. Most cells have a memory phenotype, express IgA or IgG and are present in relatively high frequencies. These data pave the path for a direct and detailed molecular characterisation of ACPA-expressing B cells and could lead to the identification of novel therapeutic targets. PMID: 26034045 [PubMed - as supplied by publisher]

Combining metagenomics with metaproteomics and stable isotope probing reveals metabolic pathways used by a naturally occurring marine methylotroph. Environ Microbiol. 2015 Jun 1; Authors: Grob C, Taubert M, Howat AM, Burns OJ, Dixon JL, Richnow HH, Jehmlich N, von Bergen M, Chen Y, Murrell JC Abstract A variety of culture-independent techniques have been developed that can be used in conjunction with culture-dependent physiological and metabolic studies of key microbial organisms, in order to better understand how the activity of natural populations influences and regulates all major biogeochemical cycles. In this study, we combined DNA-stable isotope probing with metagenomics and metaproteomics to characterize an as yet uncultivated marine methylotroph that actively incorporated carbon from (13) C-labeled methanol into biomass. By metagenomic sequencing of the heavy DNA, we retrieved virtually the whole genome of this bacterium and determined its metabolic potential. Through protein-stable isotope probing, the RuMP cycle was established as the main carbon assimilation pathway, and the classical methanol dehydrogenase-encoding gene mxaF, as well as three out of four identified xoxF homologues were found to be expressed. This proof-of-concept study is the first in which theculture-independent techniques of DNA- and protein-stable isotope probing have been used to characterize the metabolism of a naturally-ocurring Methylophaga-like bacterium in the marine environment (i.e. M. thiooxydans L4) and thus provides a powerful approach to access the genome and proteome of uncultivated microbes involved in key processes in the environment. PMID: 26033676 [PubMed - as supplied by publisher]

Metabolome disruption of the rat cerebrum induced by the acute toxic effects of the synthetic cannabinoid MAM-2201. Life Sci. 2015 May 29; Authors: Zaitsu K, Hayashi Y, Suzuki K, Nakayama H, Hattori N, Takahara R, Kusano M, Tsuchihashi H, Ishi A Abstract AIMS: The aims of this study is to investigate the metabolome disruption in rat cerebrum induced by the recently abused synthetic cannabinoid MAM-2201. MAIN METHODS: MAM-2201 was intraperitoneally administered to 6-week Wistar rats at 5 or 15 mg/kg (n=5), and the cerebrum metabolome alteration was investigated using gas chromatography/tandem mass spectrometry (GC/MS/MS)-based metabolomics technique. KEY FINDINGS AND SIGNIFICANCE: MAM-2201 induced oligopnea and hypokinesia at 5 mg/kg dose, while more abnormal symptoms like rotational and seizure-like behaviors were observed at 15 mg/kg dose, suggesting that MAM-2201 induced neurofunctional disruptions. GC/MS/MS detected 72 metabolites in the rat cerebrum. The cerebrum levels of 12 of these metabolites, including intermediates of the tricarboxylic acid cycle (malic acid and succinic acid) and glutamic acid (Glu), were significantly changed in MAM-2201 administered groups compared to the control groups. The synthetic cannabinoid MAM-2201 can disrupt not only glutamatergic neurotransmission but also energy metabolism in the rat cerebrum. Such disruption may contribute to the abnormal symptoms induced by synthetic cannabinoids. PMID: 26032255 [PubMed - as supplied by publisher]

Metabolomic profiling and genomic analysis of wheat aneuploid lines to identify genes controlling biochemical pathways in mature grain. Plant Biotechnol J. 2015 Jun 1; Authors: Francki MG, Hayton S, Gummer JP, Rawlinson C, Trengove RD Abstract Metabolomics is becoming an increasingly important tool in plant genomics to decipher the function of genes controlling biochemical pathways responsible for trait variation. Although theoretical models can integrate genes and metabolites for trait variation, biological networks require validation using appropriate experimental genetic systems. In this study, we applied an untargeted metabolite analysis to mature grain of wheat homoeologous group 3 ditelosomic lines, selected compounds that showed significant variation between wheat lines Chinese Spring and at least one ditelosomic line, tracked the genes encoding enzymes of their biochemical pathway using the wheat genome survey sequence and determined the genetic components underlying metabolite variation. A total of 412 analytes were resolved in the wheat grain metabolome, and principal component analysis indicated significant differences in metabolite profiles between Chinese Spring and each ditelosomic lines. The grain metabolome identified 55 compounds positively matched against a mass spectral library where the majority showed significant differences between Chinese Spring and at least one ditelosomic line. Trehalose and branched-chain amino acids were selected for detailed investigation, and it was expected that if genes encoding enzymes directly related to their biochemical pathways were located on homoeologous group 3 chromosomes, then corresponding ditelosomic lines would have a significant reduction in metabolites compared with Chinese Spring. Although a proportion showed a reduction, some lines showed significant increases in metabolites, indicating that genes directly and indirectly involved in biosynthetic pathways likely regulate the metabolome. Therefore, this study demonstrated that wheat aneuploid lines are suitable experimental genetic system to validate metabolomics-genomics networks. PMID: 26032167 [PubMed - as supplied by publisher]

LC-MS untargeted metabolomic analysis of drug-induced hepatotoxicity in HepG2 cells. Electrophoresis. 2015 Jun 1; Authors: García-Cañaveras JC, Jiménez N, Gómez-Lechón MJ, Castell JV, Donato MT, Lahoz A Abstract Hepatotoxicity is the number one cause for agencies not approving and withdrawing drugs for the market. Drug-induced human hepatotoxicity frequently goes undetected in pre-clinical safety evaluations using animal models. Human-derived in vitro models represent a common alternative to in vivo tests to detect toxic effects during pre-clinical testing. Most current in vitro toxicity assays rely on the measurement of nonspecific or low sensitive endpoints, which result in poor concordance with human liver toxicity. Therefore, making more accurate predictions of the potential hepatotoxicity of new drugs remains a challenge. Metabolomics, whose aim is to globally assess all the metabolites in a biological sample, may represent an alternative in the search for sensitive sublethal markers of drug-induced hepatotoxicity. To this end, a comprehensive LC-MS-based untargeted metabolite profiling analysis of HepG2 cells, exposed to a set of well-described model hepatotoxins and innocuous compounds, was performed. It allowed to determine meaningful metabolic changes triggered by a toxic insult and gave a first estimation of the main toxicity-related pathways. Based on these metabolic patterns, a PLS-DA model, able to discriminate between nontoxic and hepatotoxic compounds, was constructed. The approach described herein may provide an alternative for animal testing in pre-clinical stages of drug development and a controlled experimental approach to gain a profound understanding of the underlying causes of hepatotoxicity. This article is protected by copyright. All rights reserved. PMID: 26031481 [PubMed - as supplied by publisher]

[Obesity as pathology of adipocytes: number of cells, volume of arterial bloodstream,local pools of circulation in vivo, natriuretic peptides and arterial hypertension]. Klin Lab Diagn. 2015 Mar;60(3):4-13 Authors: Titov VN, Dmitriev VA Abstract The non-specific systemic biological reaction of arterial pressure from the level of organism. vasomotor center and proximal section of arterial bloodstream is appealed to compensate disorders of metabolism and microcirculation in distal section of arteries. This phenomenon occurs in several cases. The primarily local disorders of metabolism at autocrine level, physiological (aphysiological) death of cells, "littering" of intercellular medium become the cause of disorder of microcirculation in paracrin cenosises and deteriorate realization of biological functions of homeostasis, trophology, endoecology and adaptation. The local compensation of affected perfusion in paracrin cenosises at the expense of function of peripheral peristaltic pumps, redistribution of local bloodflow in biological reaction of endothelium-depended vaso-dilation has no possibility to eliminate disorders in realization of biological functions. The systemic increase of arterial pressure under absence of specific symptoms of symptomatic arterial hypertension is a test to detect disorder of biological functions of homeostasis, trophology, biological function of endoecology and adaptation. Allforms of arterial hypertension develop by common algorithm independently from causes of disorders of blood flow, microcirculation in distal section of arteries. The non-specific systemic compensation ofdisorders of metabolism from level of organism, in proximal section of arterial bloodstream always is the same one and results in aphysiological alterations in organs-targets. To comprehend etiological characteristics of common pathogenesis of arterial hypertension is possible in case of application of such technically complicated and still unclear in differential diagnostic of deranged functions modes of metabolomics. PMID: 26031157 [PubMed - in process]

Related Articles Multiple mass isotopomer tracing of acetyl-CoA metabolism in Langendorff-perfused rat hearts: channeling of acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. J Biol Chem. 2015 Mar 27;290(13):8121-32 Authors: Li Q, Deng S, Ibarra RA, Anderson VE, Brunengraber H, Zhang GF Abstract We developed an isotopic technique to assess mitochondrial acetyl-CoA turnover (≈citric acid flux) in perfused rat hearts. Hearts are perfused with buffer containing tracer [(13)C2,(2)H3]acetate, which forms M5 + M4 + M3 acetyl-CoA. The buffer may also contain one or two labeled substrates, which generate M2 acetyl-CoA (e.g. [(13)C6]glucose or [1,2-(13)C2]palmitate) or/and M1 acetyl-CoA (e.g. [1-(13)C]octanoate). The total acetyl-CoA turnover and the contributions of fuels to acetyl-CoA are calculated from the uptake of the acetate tracer and the mass isotopomer distribution of acetyl-CoA. The method was applied to measurements of acetyl-CoA turnover under different conditions (glucose ± palmitate ± insulin ± dichloroacetate). The data revealed (i) substrate cycling between glycogen and glucose-6-P and between glucose-6-P and triose phosphates, (ii) the release of small excess acetyl groups as acetylcarnitine and ketone bodies, and (iii) the channeling of mitochondrial acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. Because of this channeling, the labeling of acetylcarnitine and ketone bodies released by the heart are not proxies of the labeling of mitochondrial acetyl-CoA. PMID: 25645937 [PubMed - indexed for MEDLINE]

GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort. PLoS One. 2015;10(6):e0127299 Authors: Nezami Ranjbar MR, Luo Y, Di Poto C, Varghese RS, Ferrarini A, Zhang C, Sarhan NI, Soliman H, Tadesse MG, Ziada DH, Roy R, Ressom HW Abstract This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC) cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS). Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS) and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS). Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM) mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA) metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC. PMID: 26030804 [PubMed - as supplied by publisher]

Myo-inositol improves the host's ability to eliminate balofloxacin-resistant Escherichia coli. Sci Rep. 2015;5:10720 Authors: Chen XH, Zhang BW, Li H, Peng XX Abstract Antibiotic-resistant mechanisms are associated with fitness costs. However, why antibiotic-resistant bacteria usually show increasing adaptation to hosts is largely unknown, especially from the host's perspective. The present study reveals the host's varied response to balofloxacin-resistant Escherichia coli (BLFX-R) using an integrated proteome and metabolome approach and identifies myo-inositol and phagocytosis-related proteins as crucial biomarkers. Originally, macrophages have an optimal attractive preference to BLFX-S due to more polarization of BLFX-S than BLFX-R, which renders faster elimination to BLFX-S than BLFX-R. The slower elimination to BLFX-R may be reversed by exogenous myo-inositol. Primarily, myo-inositol depolarizes macrophages, elevating adherence to both BLFX-S and BLFX-R. Since the altered adherence is equal to both strains, the myo-inositol-treated macrophages are free of the barrier to BLFX-R and thereby promote phagocytosis of BLFX-R. This work provides a novel strategy based on metabolic modulation for eliminating antibiotic-resistant bacteria with a high degree of host adaptation. PMID: 26030712 [PubMed - as supplied by publisher]