PubMed

Related Articles Application of GC/MS-based metabonomic profiling in studying the therapeutic effects of Huangbai-Zhimu herb-pair (HZ) extract on streptozotocin-induced type 2 diabetes in mice. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 1;997:96-104 Authors: Song L, Liu H, Wang Y, Wang Y, Liu J, Zhou Z, Chu H, Zhuang P, Zhang Y Abstract A protocol for metabolic profiling of mice urine was developed based on gas chromatograph-mass spectrometer (GC-MS) to explore metabolic state directly. The intra-day, inter-day, repeatability, and stability RSD for most endogenous compounds were less than 3%. Type 2 diabetic mellitus (T2DM) mice model was induced by high calorie diet combined with streptozocin. Urine from the control, T2DM and Huangbai-Zhimu herb-pair (HZ) treatment mice were enrolled in the subsequent study to show the usefulness of the method. OPLS-DA scores plots demonstrate that the cluster of T2DM mice is separated from that of control mice, while HZ-T2DM mice are located close to control mice, indicating that metabolic profiles of these HZ-T2DM mice are placed toward those of control group. The results illustrate that HZ treatment could lower the level of d-glucose, hexadecanoic acid, octadecanoic acid, propanoic acid, 3-hydroxybutyric acid, and 2,3-dihydroxybutanoic acid in urine of DM mice, meanwhile the results show that HZ treatment could ameliorate T2DM symptoms by intervening the fatty acid metabolism, starch and sucrose metabolism, and glyoxylate and dicarboxylate metabolism. This preliminary application indicated that the method is suitable and reliable for urine metabolic profiling. This study might explain the metabolic effects of T2DM and the mechanisms of action of HZ against T2DM. PMID: 26094210 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/01/13PubMed 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.

Related Articles Volatile Organic Compounds (VOC) as new biomarkers for colorectal cancer: a review. Colorectal Dis. 2016 Jan 11; Authors: Di Lena M, Porcelli F, Altomare DF Abstract AIM: The analysis of the volatile part of the metabolome (Volatile Organic Compounds (VOC)) present in the gas phase of excreted materials is a promising new research field for the identification of screening tools for several cancers, including colorectal cancer (CRC). The VOC signature can reflect the health status as a 'fingerprint', which can be modified in several diseases. Technical difficulties still limit the widespread use of VOC analysis in the clinical setting, but this approach has already been applied successfully in the diagnosis of CRC. The present study reviews the available data on VOC present in DEAR AUITHOR THE WORD 'HEADSPACE' IS NOT ENGLISH AS FAR AS I KNOW. IF YOU WANT TO INCLUDE A WORD THAT IS RECOGNISED THEN PLEASE LET ME KNOW. OTHERWISE I WILL REMOVE IT FROM THE TEXT. Headspace is the word used to identify "the gaseous constituents of a closed space above liquids or solid emitting and vapors measured using headspace gas chromatography" the headspace (the gaseous constituents of a closed space above a liquid or solid) of blood, urine, faeces and breath as a potential screening tool for CRC. METHOD: A systematic electronic literature search was conducted in PubMed, Scirus and Google using the keywords Metabolomic, Volatile Organic Compounds (VOC), Electronic-nose and Colorectal Cancer. Only articles published in English between 2000-2015 were selected and independently checked by two of the authors. RESULTS: Ten papers describing the reliability of VOC analysis in breath and faeces, blood and urine were selected, all indicating good reliability in detecting colorectal cancer. The use of different substrates and different analytical platforms has led to the identification of different patterns of VOC. CONCLUSION: The reliability of a metabolomic approach in CRC screening as a non-invasive biomarker is supported by this review despite several limitation due to the number of patients included in each study, the different analytical platforms and the biological material used and different VOCs identified This article is protected by copyright. All rights reserved. PMID: 26752703 [PubMed - as supplied by publisher]

Related Articles Metabolic Analysis of Medicinal Dendrobium officinale and Dendrobium huoshanense during Different Growth Years. PLoS One. 2016;11(1):e0146607 Authors: Jin Q, Jiao C, Sun S, Song C, Cai Y, Lin Y, Fan H, Zhu Y Abstract Metabolomics technology has enabled an important method for the identification and quality control of Traditional Chinese Medical materials. In this study, we isolated metabolites from cultivated Dendrobium officinale and Dendrobium huoshanense stems of different growth years in the methanol/water phase and identified them using gas chromatography coupled with mass spectrometry (GC-MS). First, a metabolomics technology platform for Dendrobium was constructed. The metabolites in the Dendrobium methanol/water phase were mainly sugars and glycosides, amino acids, organic acids, alcohols. D. officinale and D. huoshanense and their growth years were distinguished by cluster analysis in combination with multivariate statistical analysis, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Eleven metabolites that contributed significantly to this differentiation were subjected to t-tests (P<0.05) to identify biomarkers that discriminate between D. officinale and D. huoshanense, including sucrose, glucose, galactose, succinate, fructose, hexadecanoate, oleanitrile, myo-inositol, and glycerol. Metabolic profiling of the chemical compositions of Dendrobium species revealed that the polysaccharide content of D. huoshanense was higher than that of D. officinale, indicating that the D. huoshanense was of higher quality. Based on the accumulation of Dendrobium metabolites, the optimal harvest time for Dendrobium was in the third year. This initial metabolic profiling platform for Dendrobium provides an important foundation for the further study of secondary metabolites (pharmaceutical active ingredients) and metabolic pathways. PMID: 26752292 [PubMed - as supplied by publisher]

Related Articles Urinary Biomarkers of Brain Diseases. Genomics Proteomics Bioinformatics. 2016 Jan 2; Authors: An M, Gao Y Abstract Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome. PMID: 26751805 [PubMed - as supplied by publisher]

Related Articles Influence of weight reduction on blood levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and oxylipins in obese subjects. Prostaglandins Leukot Essent Fatty Acids. 2015 Dec 17; Authors: Möller K, Ostermann AI, Rund K, Thoms S, Blume C, Stahl F, Hahn A, Schebb NH, Schuchardt JP Abstract INTRODUCTION: Obesity is associated with inflammation and weight reduction has been shown to influence the inflammatory process. Besides classic inflammatory markers, oxidized polyunsaturated fatty acid (PUFA) metabolites (oxylipins) are potent mediators of inflammation. Little is known about endogenous levels of oxylipins, e.g. hydroxy, epoxy and dihydroxy FA in obese subjects with persistent low-grade inflammation. We aimed to evaluate levels of inflammatory markers and blood oxylipins in obese subjects before and after weight reduction. SUBJECTS AND METHODS: In the present study, 42 obese (BMI 32.7±0.22kg/m(2)) men and women were classified in groups according to high-sensitivity C-reactive protein (hsCRP) levels (no inflammation<1mg/L; low-grade inflammation≥3mg/L). Subjects underwent an intervention for eight weeks, which consisted of two phases: (1) week 1 and 2: total replacement of three meals by a formula diet and (2) six week partial formula diet (replacement of 1-2 meals). Blood samples were taken prior and post intervention for analysis of plasma protein levels of hsCRP, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Plasma Levels of free (unesterified) hydroxy, epoxy, and dihydroxy FAs as well as several prostanoids were analyzed in plasma by means of LC-MS-based targeted metabolomics. RESULTS: At baseline subjects with low-grade inflammation (hsCRP 8.95±1.39mg/L) showed significant higher levels of IL-6 (22.7±1.15ng/L) and TNF-α (17.4±0.75ng/L) compared to subjects with no inflammation (hsCRP: 0.69±0.05mg/L; IL-6: 15.9±1.18ng/L; TNF-α: 14.6±0.80ng/L). In both group's body weight was significantly reduced (p<0.001) after intervention (no inflammation group: -7.19±0.86kg, -7.3±0.89%, p<0.001; low-grade inflammation group: -6.78±0.87kg, -6.7±0.81%, p<0.001). Moreover, we observed significant decreases in levels of hsCRP (4.66±0.64mg/L; p=0.006), IL-6 (6.81±1.15ng/L; p<0.001) and TNF-α (6.09±0.47ng/L; p<0.001) in subjects with low-grade inflammation. Of 60 quantified oxylipins, 11 linoleic acid (LA)-, 1 dihomo-γ-linolenic acid (DGLA)-, 7 alpha linolenic acid (ALA)-, 15 arachidonic acid (AA)-, 8 eicosapentaenoic acid (EPA)- and 18 docosahexaenoic acid (DHA)-metabolites could be detected in plasma. For most oxylipins no differences were found between the low and high hsCRP groups before and after weight reduction. Interestingly, in subjects with low- grade inflammation several AA-derived oxylipins (5-, 8-, 12-hydroxyeicosatetraenoic acids (HETE)) were significantly higher compared to subjects with no inflammation before weight reduction and significantly reduced after weight reduction. CONCLUSION: Even moderate weight loss in obese subjects correlates to a significant improvement in the inflammatory state, by reducing hsCRP, IL-6, TNF-α and few oxylipins. The biological consequences of these changes remain to be further investigated. PMID: 26751601 [PubMed - as supplied by publisher]

Related Articles Advances in mass spectrometry-based clinical biomarker discovery. Clin Proteomics. 2016;13:1 Authors: Crutchfield CA, Thomas SN, Sokoll LJ, Chan DW Abstract The greatest unmet needs in biomarker discovery are those discoveries that lead to the development of clinical diagnostic tests. These clinical diagnostic tests can provide early intervention when a patient would present otherwise healthy (e.g., cancer or cardiovascular disease) and aid clinical decision making with improved clinical outcomes. The past two decades have seen significant technological improvements in the analytical capabilities of mass spectrometers. Mass spectrometers are unique in that they can directly analyze any biological molecule susceptible to ionization. The biological studies of human metabolites and proteins using contemporary mass spectrometry technology (metabolomics and proteomics, respectively) has been ongoing for over a decade. Some of these studies have resulted in exciting insights into human biology. However, relatively few biomarkers have been translated into clinical tests. This review will discuss some key technological developments that have occurred over this time with an emphasis on technologies that will create new avenues for biomarker discovery. PMID: 26751220 [PubMed - as supplied by publisher]

Related Articles 1H NMR and GC-MS based metabolomics reveal defense and detoxification mechanism of cucumber plant under nano-Cu stress. Environ Sci Technol. 2016 Jan 11; Authors: Zhao L, Huang Y, Hu J, Zhou H, Adeleye AS, Keller AA Abstract Since copper nanoparticles are being increasingly used in agriculture as pesticides, it is important to assess their potential implications for agriculture. Concerns have been raised about the bioaccumulation of nano-Cu and their toxicity to crop plants. Here, the response of cucumber plants in hydroponic culture at early development stages to two concentrations of nano-Cu (10 and 20 mg/L) was evaluated by proton nuclear magnetic resonance spectroscopy (1H NMR) and Gas Chromatography-Mass Spectrometry (GC-MS) based metabolomics. Changes in mineral nutrient metabolism induced by nano-Cu were determined by ICP-OES. Results showed that nano-Cu at both concentrations interfere with the uptake of a number of micro- and macro-nutrients, such as Na, P, S, Mo, Zn, and Fe. Metabolomics data revealed that nano-Cu at both levels triggered significant metabolic changes in cucumber leaves and root exudates. The root exudate metabolic changes revealed an active defense mechanism against nano-Cu stress: up-regulation of amino acids to sequester/exclude Cu/nano-Cu; down-regulation of citric acids to reduce the mobilization of Cu ions; ascorbic acid up-regulation to combat reactive oxygen species; up-regulation of phenolic compounds to improve antioxidant system. Thus, we demonstrate that non-targeted 1H NMR and GC-MS based metabolomics can successfully identify physiological responses induced by nanoparticles. Root exudates metabolomics revealed important detoxification mechanisms. PMID: 26751164 [PubMed - as supplied by publisher]

Related Articles Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease. PLoS One. 2016;11(1):e0141738 Authors: Missailidis C, Hällqvist J, Qureshi AR, Barany P, Heimbürger O, Lindholm B, Stenvinkel P, Bergman P Abstract BACKGROUND: The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. OBJECTIVE: To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. METHODS: Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3-5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. RESULTS: GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3-5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32-14.2; p = 0.016). CONCLUSION: Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3-5 patients. PMID: 26751065 [PubMed - as supplied by publisher]

Related Articles An integrated chinmedomics strategy for discovery of effective constituents from traditional herbal medicine. Sci Rep. 2016;6:18997 Authors: Wang X, Zhang A, Zhou X, Liu Q, Nan Y, Guan Y, Kong L, Han Y, Sun H, Yan G Abstract Traditional natural product discovery affords no information about compound structure or pharmacological activities until late in the discovery process, and leads to low probabilities of finding compounds with unique biological properties. By integrating serum pharmacochemistry-based screening with high-resolution metabolomics analysis, we have developed a new platform, termed chinmedomics which is capable of directly discovering the bioactive constituents. In this work, the focus is on ShenQiWan (SQW) treatment of ShenYangXu (SYX, kidney-yang deficiency syndrome) as a case study, as determined by chinmedomics. With serum pharmacochemistry, a total of 34 peaks were tentatively characterised in vivo, 24 of which were parent components and 10 metabolites were detected. The metabolic profiling and potential biomarkers of SYX were also investigated and 23 differential metabolites were found. 20 highly correlated components were screened by the plotting of correlation between marker metabolites and serum constituents and considered as the main active components of SQW. These compounds are imported into a database to predict the action targets: 14 importantly potential targets were found and related to aldosterone-regulated sodium reabsorption and adrenergic signaling pathways. Our study showed that integrated chinmedomics is a powerful strategy for discovery and screening of effective constituents from herbal medicines. PMID: 26750403 [PubMed - in process]

Related Articles [Cardiotoxicity study of Shenfu compatibility in rats based on metabonomics]. Zhongguo Zhong Yao Za Zhi. 2015 Jul;40(14):2743-7 Authors: He JL, Zhao JW, Ma ZC, Liang QD, Wang YG, Tan HL, Xiao CR, Tang Xiang-lin, Gao Y Abstract To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity. PMID: 26666020 [PubMed - indexed for MEDLINE]

Related Articles Cyclic diGMP regulates production of sortase substrates of Clostridium difficile and their surface exposure through ZmpI protease-mediated cleavage. J Biol Chem. 2015 Oct 2;290(40):24453-69 Authors: Peltier J, Shaw HA, Couchman EC, Dawson LF, Yu L, Choudhary JS, Kaever V, Wren BW, Fairweather NF Abstract In Gram-positive pathogens, surface proteins may be covalently anchored to the bacterial peptidoglycan by sortase, a cysteine transpeptidase enzyme. In contrast to other Gram-positive bacteria, only one single sortase enzyme, SrtB, is conserved between strains of Clostridium difficile. Sortase-mediated peptidase activity has been reported in vitro, and seven potential substrates have been identified. Here, we demonstrate the functionality of sortase in C. difficile. We identify two sortase-anchored proteins, the putative adhesins CD2831 and CD3246, and determine the cell wall anchor structure of CD2831. The C-terminal PPKTG sorting motif of CD2831 is cleaved between the threonine and glycine residues, and the carboxyl group of threonine is amide-linked to the side chain amino group of diaminopimelic acid within the peptidoglycan peptide stem. We show that CD2831 protein levels are elevated in the presence of high intracellular cyclic diGMP (c-diGMP) concentrations, in agreement with the control of CD2831 expression by a c-diGMP-dependent type II riboswitch. Low c-diGMP levels induce the release of CD2831 and presumably CD3246 from the surface of cells. This regulation is mediated by proteolytic cleavage of CD2831 and CD3246 by the zinc metalloprotease ZmpI, whose expression is controlled by a type I c-diGMP riboswitch. These data reveal a novel regulatory mechanism for expression of two sortase substrates by the secondary messenger c-diGMP, on which surface anchoring is dependent. PMID: 26283789 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of antioxidants constituents in Artemisia selengensis leaves. Food Chem. 2015 Nov 1;186:123-32 Authors: Zhang L, Tu ZC, Wang H, Fu ZF, Wen QH, Fan D Abstract This study aimed to evaluate the antioxidant potential of Artemisia selengensis Turcz (AST) leaves, a byproduct when processing AST stalk, and identify the antioxidant constituents by using HPLC-QTOF-MS(2). The total phenolics content (TPC), total flavonoids content (TFC) and antioxidant abilities of fractions resulted from the successively partition of chloroform, ethyl acetate and n-butanol were compared. Ethyl acetate fraction (EAF) exhibited the highest TFC (65.44 mg QuE/g fraction), n-butanol fraction (nBuF) showed the highest TPC (384.78 mg GAE/g fraction) and the best DPPH scavenging ability, ABTS(+) scavenging ability and reducing power. Totally, 57 compounds were identified or tentatively identified in nBuF and EAF, 40 of them were reported in AST for the first time. The major constituents in EAF were flavonoids, and the major constituents in nBuF were phenolic acids and organic acids. Thus, AST leaves might be a potential low-cost resource of natural antioxidants. PMID: 25976801 [PubMed - indexed for MEDLINE]

Related Articles Metabonomic Study of the Effects of Acanthopanax senticosus on Peripheral System of Rats. Planta Med. 2015 Jun;81(9):722-32 Authors: Zhang SN, Li XZ, Liu SM, Lu F Abstract Acanthopanax senticosus is extensively used to treat various nervous and cerebrovascular diseases in traditional medicinal systems in China and Russia. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry coupled with pattern recognition methods was used to investigate the effects of A. senticosus on the peripheral system in rats. The analysis of possible pathways influenced by A. senticosus was performed with MetaboAnalyst and Cytoscape software. After treatment with A. senticosus, 21 modulated metabolites in heart tissue, 20 in liver tissue, 14 in spleen tissue, 17 in lung tissue, 16 in kidney tissue, and 12 in a serum sample were identified and considered potential biomarkers of A. senticosus treatments. The regulation of some endogenous metabolites by A. senticosus could be beneficial for the treatment of several peripheral system diseases, such as hypertension, cancer, and oxidative stress, etc. However, there were also some upregulated endogenous metabolites producing potential toxicity to the peripheral system. A metabonomic analysis revealed that protection and toxicity coexisted in the effects of A. senticosus on the peripheral system, which may be a practical guide for its safe use and beneficial to the expansion of its application. PMID: 25922912 [PubMed - indexed for MEDLINE]

Related Articles ¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice. Int J Biol Sci. 2015;11(5):595-603 Authors: Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L Abstract Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism. PMID: 25892966 [PubMed - indexed for MEDLINE]

Related Articles How to measure metabolic fluxes: a taxonomic guide for (13)C fluxomics. Curr Opin Biotechnol. 2015 Aug;34:82-90 Authors: Niedenführ S, Wiechert W, Nöh K Abstract Metabolic reaction rates (fluxes) contribute fundamentally to our understanding of metabolic phenotypes and mechanisms of cellular regulation. Stable isotope-based fluxomics integrates experimental data with biochemical networks and mathematical modeling to 'measure' the in vivo fluxes within an organism that are not directly observable. In recent years, (13)C fluxomics has evolved into a technology with great experimental, analytical, and mathematical diversity. This review aims at establishing a unified taxonomy by means of which the various fluxomics methods can be compared to each other. By linking the developed modeling approaches to recent studies, their challenges and opportunities are put into perspective. The proposed classification serves as a guide for scientific 'travelers' who are striving to resolve research questions with the currently available (13)C fluxomics toolset. PMID: 25531408 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling study on potential toxicity and immunotoxicity-biomarker discovery in rats treated with cyclophosphamide using HPLC-ESI-IT-TOF-MS. Biomed Chromatogr. 2015 May;29(5):768-76 Authors: Li J, Lin W, Lin W, Xu P, Zhang J, Yang H, Ling X Abstract Despite the recent advances in understanding toxicity mechanism of cyclophosphamide (CTX), the development of biomarkers is still essential. CTX-induced immunotoxicity in rats by a metabonomics approach was investigated using high-performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry (HPLC-ESI-IT-TOF-MS). The rats were orally administered CTX (30 mg/kg/day) for five consecutive days, and on the fifth day samples of urine, thymus and spleen were collected and analyzed. A significant difference in metabolic profiling was observed between the CTX-treated group and the control group by partial least squares-discriminant analysis (PLS-DA), which indicated that metabolic disturbances of immunotoxicity in CTX-treated rats had occurred. One potential biomarker in spleen, three in urine and three in thymus were identified. It is suggested that the CTX-toxicity mechanism may involve the modulation of tryptophan metabolism, phospholipid metabolism and energy metabolism. This research can help to elucidate the CTX-influenced pathways at a low dose and can further help to indicate the patients' pathological status at earlier stages of toxicological progression after drug administration. PMID: 25322901 [PubMed - indexed for MEDLINE]

Identified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes. Transfusion. 2016 Jan 8; Authors: Bordbar A, Johansson PI, Paglia G, Harrison SJ, Wichuk K, Magnusdottir M, Valgeirsdottir S, Gybel-Brask M, Ostrowski SR, Palsson S, Rolfsson O, Sigurjónsson OE, Hansen MB, Gudmundsson S, Palsson BO Abstract BACKGROUND: There has been interest in determining whether older red blood cell (RBC) units have negative clinical effects. Numerous observational studies have shown that older RBC units are an independent factor for patient mortality. However, recently published randomized clinical trials have shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit. STUDY DESIGN AND METHODS: Twenty RBC units were profiled using quantitative metabolomics over 42 days of storage in SAGM with 3- to 4-day time intervals. Metabolic pathway usage during storage was assessed using systems biology methods. The detected time intervals of the metabolic states were compared to clinical outcomes. RESULTS: Using multivariate statistics, we identified a nonlinear decay process exhibiting three distinct metabolic states (Days 0-10, 10-17, and 17-42). Hematologic variables traditionally measured in the transfusion setting (e.g., pH, hemolysis, RBC indices) did not distinguish these three states. Systemic changes in pathway usage occurred between the three states, with key pathways changing in both magnitude and direction. Finally, an association was found between the time periods of the metabolic states with the clinical outcomes of more than 280,000 patients in the country of Denmark transfused over the past 15 years and endothelial damage markers in healthy volunteers undergoing autologous transfusions. CONCLUSION: The state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables. PMID: 26749434 [PubMed - as supplied by publisher]

Implication of Metabolomic profiles to wide thermoneutral zone in Mongolian gerbils (Meriones unguiculatus). Integr Zool. 2016 Jan 9; Authors: Shi Y, Wang D Abstract Mongolian gerbils (Meriones unguiculatus) have evolved a wide thermoneutral zone (26.5-38.9 ºC) and high upper critical temperature, and appear to have a high tolerance for heat exposure. Here, we use a metabolomic approach to measure global metabolite profiles for gerbils between lower (27 ºC) and upper critical temperatures (38 ºC) to investigate the role of metabolomic characterization in maintaining basal metabolic rates within a wide thermoneutral zone. We found that in serum and liver, 14 and 19 metabolites were significantly altered, respectively. In the aerobic respiration-related tricarboxylic cycle (TCA), five intermediates (isocitric acid, cis-aconitic acid, α-ketoglutaric acid, fumaric acid and malic acid) were increased in serum in 38 ºC animals; however, no such increase was found in the liver. A stable level of hepatic TCA cycle intermediates may be related to the steady state of aerobic respiration at 38 ºC. Metabolomic results also revealed that acute heat exposure caused increased oxidative stress and low molecular weight antioxidants in Mongolian gerbils. Increased methionine and 2-hydroxybutyrate suggest an accelerated synthesis of glutathione. Increased urate and its precursors, inosine and hypoxanthine, were detected at 38 ºC. Glucuronate, threonate and oxalate involved in ascorbate synthesis and degradation were increased in serum at 38 ºC. In conclusion, although dramatic metabolomic variation was found, a stable hepatic TCA cycle may contribute to maintaining a constant basal metabolic rate within a wide thermoneutral zone in Mongolian gerbils. This article is protected by copyright. All rights reserved. PMID: 26749160 [PubMed - as supplied by publisher]

The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins. Cell Rep. 2015 Dec 30; Authors: Davies MN, Kjalarsdottir L, Thompson JW, Dubois LG, Stevens RD, Ilkayeva OR, Brosnan MJ, Rolph TP, Grimsrud PA, Muoio DM Abstract Lysine acetylation (AcK), a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT), an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK. PMID: 26748706 [PubMed - as supplied by publisher]