PubMed

Related Articles Sulfur fumigation reducing systemic exposure of ginsenosides and weakening immunomodulatory activity of ginseng. J Ethnopharmacol. 2016 Nov 14;: Authors: Ma B, Ting Kan WL, Zhu H, Li SL, Lin G Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Ginseng Radix et Rhizoma) is used worldwide for its miracle tonic effects, especially for its immunomodulatory activities. Sulfur fumigation, a fast and convenient method to prevent pesticidal and bacterial contamination in the food industry, has been recently employed during post-harvest processing of ginseng. Our previous studies demonstrated that sulfur fumigation significantly altered the chemical profile of the bioactive ingredients in ginseng. However, the effects of sulfur fumigation on the pharmacokinetics and bioactivities of ginseng remain unknown. AIM OF THE STUDY: To examine the effects of sulfur fumigation on the pharmacokinetics and immunomodulatory activities of ginseng. MATERIALS AND METHODS: For pharmacokinetic studies, male Sprague-Dawley rats exposed to single/multiple dosages of non-fumigated ginseng (NFG) and sulfur fumigated ginseng (SFG) were investigated using HPLC-MS/MS analysis. For bioactivity studies, male ICR mice were used to compare the immunomodulatory effects of NFG or SFG under both normal and cyclophosphamide (CY)-induced immunocompromised conditions using white blood cell counts, serum cytokine levels, and spleen and thymus weight indices. RESULTS: Sulfur fumigation significantly reduced the contents of the bioactive ginsenosides in ginseng, which resulted in drastically low systemic exposure of ginsenosides in SFG-treatment group compared to NFG-treatment group. This observation was consistent with the bioactivities obtained in NFG- and SFG-treatment groups. The bioactivity studies also demonstrated the immunomodulatory effects of NFG but not SFG in the CY-induced immunosuppressed mice. CONCLUSION: Sulfur fumigation significantly reduced contents of bioactive ginsenosides in ginseng, leading to dramatic decrease in the systemic exposure of these ginsenosides in the body and detrimental reduction of immunomodulatory effects of ginseng. Our results provided scientific evidences and laid a solid foundation for the needs of thorough evaluation of the significant impact of sulfur fumigation on ginseng and other medicinal herbs. PMID: 27856301 [PubMed - as supplied by publisher]

Related Articles Characterization of the Clostridium difficile volatile metabolome using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Nov 9;1039:8-16 Authors: Rees CA, Shen A, Hill JE Abstract Clostridium difficile is a bacterial pathogen capable of causing life-threatening infections of the gastrointestinal tract characterized by severe diarrhea. Exposure to certain classes of antibiotics, advanced age, and prolonged hospitalizations are known risk factors for infection by this organism. Anecdotally, healthcare providers have reported that they can smell C. difficile infections in their patients, and several studies have suggested that there may indeed be an olfactory signal associated with C. difficile-associated diarrhea. In this study, we sought to characterize the volatile molecules produced by an epidemic strain of C. difficile (R20291) using headspace solid-phase microextraction (HS-SPME) followed by two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS). We report on a set of 77 volatile compounds, of which 59 have not previously been associated with C. difficile growth in vitro. Amongst these reported compounds, we detect both straight-chain and branched-chain carboxylic acids, as well as p-cresol, which have been the primary foci of C. difficile volatile metabolomic studies to-date. We additionally report on novel sulfur-containing and carbonyl-containing molecules that have not previously been reported for C. difficile. With the identification of these novel C. difficile-associated volatile compounds, we demonstrate the superior resolution and sensitivity of GC×GC-TOFMS relative to traditional GC-MS. PMID: 27855313 [PubMed - as supplied by publisher]

Related Articles Comparison of Chemical Compositions in Pseudostellariae Radix from Different Cultivated Fields and Germplasms by NMR-Based Metabolomics. Molecules. 2016 Nov 15;21(11): Authors: Hua Y, Hou Y, Wang S, Ma Y, Liu Z, Zou L, Liu X, Luo Y, Liu J Abstract Pseudostellariae Radix (PR) is an important traditional Chinese medicine (TCM), which is consumed commonly for its positive health effects. However, the chemical differences of PR from different cultivated fields and germplasms are still unknown. In order to comprehensively compare the chemical compositions of PR from different cultivated fields, in this study, ¹H-NMR-based metabolomics coupled with high performance liquid chromatography (HPLC) were used to investigate the different metabolites in PR from five germplasms (jr, zs1, zs2, sb, and xc) cultivated in traditional fields (Jurong, Jiangsu, JSJR) and cultivated fields (Zherong, Fujian, FJZR). A total of 34 metabolites were identified based on ¹H-NMR data, and fourteen of them were found to be different in PR from JSJR and FJZR. The relative contents of alanine, lactate, lysine, taurine, sucrose, tyrosine, linolenic acid, γ-aminobutyrate, and hyperoside in PR from JSJR were higher than that in PR from FJZR, while PR from FJZR contained higher levels of glutamine, raffinose, xylose, unsaturated fatty acid, and formic acid. The contents of Heterophyllin A and Heterophyllin B were higher in PR from FJZR. This study will provide the basic information for exploring the influence law of ecological environment and germplasm genetic variation on metabolite biosynthesis of PR and its quality formation mechanism. PMID: 27854294 [PubMed - in process]

Related Articles Role of the lipid-regulated NF-κB/IL-6/STAT3 axis in alpha-naphthyl isothiocyanate-induced liver injury. Arch Toxicol. 2016 Nov 16; Authors: Fang ZZ, Tanaka N, Lu D, Jiang CT, Zhang WH, Zhang C, Du Z, Fu ZW, Gao P, Cao YF, Sun HZ, Zhu ZT, Cai Y, Krausz KW, Yao Z, Gonzalez FJ Abstract Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1. ANIT also increased NF-κB/IL-6/STAT3 signaling, and in vitro luciferase reporter gene assays revealed that LPC 18:0 and LPC 18:1 can activate NF-κB in a concentration-dependent manner. Activation of PPARα through feeding mice a Wy-14,643-containing diet (0.1%) reduced ANIT-induced liver injury, as indicated by lowered ALT and AST levels, and liver histology. In conclusion, the present study demonstrated a role for the lipid-regulated NF-κB/IL-6/STAT3 axis in ANIT-induced hepatotoxicity, and that PPARα may be a potential therapeutic target for the prevention of drug-induced cholestatic liver injury. PMID: 27853831 [PubMed - as supplied by publisher]

Related Articles Homeostasis of metabolites in Escherichia coli on transition from anaerobic to aerobic conditions and the transient secretion of pyruvate. R Soc Open Sci. 2016 Aug;3(8):160187 Authors: Yasid NA, Rolfe MD, Green J, Williamson MP Abstract We have developed a method for rapid quenching of samples taken from chemostat cultures of Escherichia coli that gives reproducible and reliable measurements of extracellular and intracellular metabolites by (1)H NMR and have applied it to study the major central metabolites during the transition from anaerobic to aerobic growth. Almost all metabolites showed a gradual change after perturbation with air, consistent with immediate inhibition of pyruvate formate-lyase, dilution of overflow metabolites and induction of aerobic enzymes. Surprisingly, although pyruvate showed almost no change in intracellular concentration, the extracellular concentration transiently increased. The absence of intracellular accumulation of pyruvate suggested that one or more glycolytic enzymes might relocate to the cell membrane. To test this hypothesis, chromosomal pyruvate kinase (pykF) was modified to express either PykF-green fluorescent protein or PykF-FLAG fusion proteins. Measurements showed that PykF-FLAG relocates to the cell membrane within 5 min of aeration and then slowly returns to the cytoplasm, suggesting that on aeration, PykF associates with the membrane to facilitate secretion of pyruvate to maintain constant intracellular levels. PMID: 27853594 [PubMed - in process]

Related Articles Structured plant metabolomics for the simultaneous exploration of multiple factors. Sci Rep. 2016 Nov 17;6:37390 Authors: Vasilev N, Boccard J, Lang G, Grömping U, Fischer R, Goepfert S, Rudaz S, Schillberg S Abstract Multiple factors act simultaneously on plants to establish complex interaction networks involving nutrients, elicitors and metabolites. Metabolomics offers a better understanding of complex biological systems, but evaluating the simultaneous impact of different parameters on metabolic pathways that have many components is a challenging task. We therefore developed a novel approach that combines experimental design, untargeted metabolic profiling based on multiple chromatography systems and ionization modes, and multiblock data analysis, facilitating the systematic analysis of metabolic changes in plants caused by different factors acting at the same time. Using this method, target geraniol compounds produced in transgenic tobacco cell cultures were grouped into clusters based on their response to different factors. We hypothesized that our novel approach may provide more robust data for process optimization in plant cell cultures producing any target secondary metabolite, based on the simultaneous exploration of multiple factors rather than varying one factor each time. The suitability of our approach was verified by confirming several previously reported examples of elicitor-metabolite crosstalk. However, unravelling all factor-metabolite networks remains challenging because it requires the identification of all biochemically significant metabolites in the metabolomics dataset. PMID: 27853298 [PubMed - in process]

Related Articles Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction. Sci Rep. 2016 Nov 17;6:36937 Authors: Duszka K, Picard A, Ellero-Simatos S, Chen J, Defernez M, Paramalingam E, Pigram A, Vanoaica L, Canlet C, Parini P, Narbad A, Guillou H, Thorens B, Wahli W Abstract Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes. PMID: 27853235 [PubMed - in process]

Related Articles Photoperiod affects the phenotype of mitochondrial complex I mutants. Plant Physiol. 2016 Nov 16;: Authors: Pétriacq P, De Bont L, Genestout L, Hao J, Laureau C, Florez-Sarasa I, Rzigui T, Queval G, Gilard F, Mauve C, Guérard F, Lamothe-Sibold M, Marion J, Fresneau C, Brown SC, Danon A, Krieger-Liszkay A, Berthomé R, Ribas-Carbo M, Tcherkez GG, Cornic G, Pineau B, Gakiere B, De Paepe R Abstract Plant mutants for genes encoding subunits of mitochondrial Complex I (CI, NADH:ubiquinone oxidoreductase), the first enzyme of the respiratory chain, display various phenotypes depending on growth conditions. Here, we examined the impact of photoperiod, a major environmental factor controlling plant development, on two Arabidopsis thaliana CI mutants: a new insertion mutant interrupted in both ndufs8.1 and ndufs8.2 genes encoding the NDUFS8 subunit, and the previously characterized ndufs4 CI mutant. In long day (LD) condition, both ndufs8.1 and ndufs8.2 single mutants were indistinguishable from Col-0 at phenotypic and biochemical levels, whereas the ndufs8.1 ndufs8.2 double mutant was devoid of detectable holo-CI assembly/activity, showed higher AOX content/activity and displayed a growth-retardation phenotype similar to that of the ndufs4 mutant. Although growth was more affected in ndufs4 than ndufs8.1 ndufs8.2 under short day (SD) condition, both mutants displayed a similar impairment of growth acceleration after transfer to LD as compared to the WT. Untargeted and targeted metabolomics showed that overall metabolism was less responsive to the SD-to-LD transition in mutants than in the WT. The typical LD acclimation of carbon, nitrogen-assimilation and redox-related parameters was not observed in ndufs8.1 ndufs8. Similarly, NAD(H) content, that was higher in SD condition in both mutants than in Col-0, did not adjust under LD. We propose that altered redox homeostasis and NAD(H) content/redox state control the phenotype of Complex I mutants and photoperiod acclimation in Arabidopsis. PMID: 27852950 [PubMed - as supplied by publisher]

Related Articles Metabolic reprogramming by folate restriction leads to a less aggressive cancer phenotype. Mol Cancer Res. 2016 Nov 16;: Authors: Ashkavand Z, O'Flanagan C, Hennig M, Du X, Hursting SD, Krupenko SA Abstract Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration and survival in many cell types. Here the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: non-invasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wntliver) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors. NMR-based metabolomics was used to quantitate 41 major metabolites in cells grown in folate-free medium versus standard medium. Each cell line demonstrated metabolic reprogramming when grown in folate-free medium. In E-Wnt, M-Wnt and metM-Wntliver cells 12, 29, and 25 metabolites, respectively, were significantly different (p<0.05 and at least 1.5-fold change). The levels of eight metabolites (aspartate, ATP, creatine, creatine phosphate, formate, serine, taurine and beta-alanine) were changed in each folate-restricted cell line. Increased glucose, decreased lactate, and inhibition of glycolysis, cellular proliferation, migration and invasion occurred in M-Wnt and metM-Wntliver cells (but not E-Wnt cells) grown in folate-free versus standard medium. These effects were accompanied by altered levels of several folate-metabolizing enzymes, indicating that the observed metabolic reprogramming may result from both decreased folate availability and altered folate metabolism. These findings reveal that folate restriction results in metabolic and bioenergetic changes and a less aggressive cancer cell phenotype. IMPLICATIONS: Metabolic reprogramming driven by folate restriction represents a therapeutic target for reducing the burden of breast cancer. PMID: 27852646 [PubMed - as supplied by publisher]

Related Articles Negative regulation of type I IFN signaling by phosphorylation of STAT2 on T387. EMBO J. 2016 Nov 16;: Authors: Wang Y, Nan J, Willard B, Wang X, Yang J, Stark GR Abstract The transcription factor ISGF3, comprised of IRF9 and tyrosine-phosphorylated STATs 1 and 2, transmits the signal from the type I interferon receptor to the genome. We have discovered a novel phosphorylation of STAT2 on T387 that negatively regulates this response. In most untreated cell types, the majority of STAT2 is phosphorylated on T387 constitutively. In response to interferon-β, the T387A mutant of STAT2 is much more effective than wild-type STAT2 in mediating the expression of many interferon-stimulated genes, in protecting cells against virus infection, and in inhibiting cell growth. Interferon-β-treated cells expressing wild-type STAT2 contain much less ISGF3 capable of binding to an interferon-stimulated response element than do cells expressing T387A STAT2. T387 lies in a cyclin-dependent kinase (CDK) consensus sequence, and CDK inhibitors decrease T387 phosphorylation. Using CDK inhibitors to reverse the constitutive inhibitory phosphorylation of T387 of U-STAT2 might enhance the efficacy of type I interferons in many different clinical settings. PMID: 27852626 [PubMed - as supplied by publisher]

Related Articles A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction. Int J Cardiol. 2016 Nov 11;: Authors: Nam M, Jung Y, Ryu DH, Hwang GS Abstract BACKGROUND: Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. METHODS: We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. RESULTS: A time-dependent increase or decrease in polar and lipid metabolite levels was measured. The S-adenosylmethionine (SAM) concentration and the SAM/S-adenosylhomocysteine (SAH) ratio gradually decreased in a time-dependent manner and were significantly downregulated 10days after MI. Transcriptome analysis revealed that the levels of coenzyme Q (Coq)-3 and Coq5, both of which are SAM-dependent methyltransferases, were decreased in the MI groups. These results suggested that dysregulation of SAM may be related to down regulated COQ biosynthetic pathway. In addition, short-chain (C3) and medium-chain (C4-C12) acylcarnitine levels gradually decreased, whereas long-chain acylcarnitine (C14-18) levels increased, owing to a defect in β-oxidation during ischemia. These changes are related to energy-dependent metabolic pathways, and a subsequent decrease in adenosine triphosphate concentration was observed. CONCLUSIONS: The comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI. PMID: 27852445 [PubMed - as supplied by publisher]

Related Articles Metabolic Profiling of Liver Tissue in Diabetic Mice Treated with Artemisia Capillaris and Alisma Rhizome Using LC-MS and CE-MS. Am J Chin Med. 2016 Nov 16;:1-23 Authors: Kim Y, Lee IS, Kim KH, Park J, Lee JH, Bang E, Jang HJ, Na YC Abstract Artemisia Capillaris (AC) and Alisma Rhizome (AR) are natural products for the treatment of liver disorders in oriental medicine clinics. Here, we report metabolomic changes in the evaluation of the treatment effects of AC and AR on fatty livers in diabetic mice, along with a proposition of the underlying metabolic pathway. Hydrophobic and hydrophilic metabolites extracted from mouse livers were analyzed using HPLC-QTOF and CE-QTOF, respectively, to generate metabolic profiles. Statistical analysis of the metabolites by PLS-DA and OPLA-DA fairly discriminated between the diabetic, and the AC- and AR-treated mice groups. Various PEs mostly contributed to the discrimination of the diabetic mice from the normal mice, and besides, DG (18:1/16:0), TG (16:1/16:1/20:1), PE (21:0/20:5), and PA (18:0/21:0) were also associated with discrimination by s-plot. Nevertheless, the effects of AC and AR treatment were indistinct with respect to lipid metabolites. Of the 97 polar metabolites extracted from the CE-MS data, 40 compounds related to amino acid, central carbon, lipid, purine, and pyrimidine metabolism, with [Formula: see text] values less than 0.05, were shown to contribute to liver dysregulation. Following treatment with AC and AR, the metabolites belonging to purine metabolism preferentially recovered to the metabolic state of the normal mice. The AMP/ATP ratio of cellular energy homeostasis in AR-treated mice was more apparently increased ([Formula: see text]) than that of AC-treated mice. On the other hand, amino acids, which showed the main alterations in diabetic mice, did not return to the normal levels upon treatment with AR or AC. In terms of metabolomics, AR was a more effective natural product in the treatment of liver dysfunction than AC. These results may provide putative biomarkers for the prognosis of fatty liver disorder following treatment with AC and AR extracts. PMID: 27852124 [PubMed - as supplied by publisher]

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming. Oncotarget. 2016 Nov 11;: Authors: Thiagarajan PS, Wu X, Zhang W, Shi I, Bagai R, Leahy P, Feng Y, Veigl M, Lindner D, Danielpour D, Yin L, Rosell R, Bivona TG, Zhang Z, Ma PC Abstract The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming. Cells undergoing early adaptive drug escape are in proliferative-metabolic quiescent, with enhanced EMT-ness and stem cell signaling, exhibiting global bioenergetics suppression including reverse Warburg, and are susceptible to glutamine deprivation and TGFβ2 inhibition. Our study further supports a preemptive therapeutic targeting of bioenergetics and mitochondrial priming to impact early drug-escape emergence using EGFR precision inhibitor combined with broad BH3-mimetic to interrupt BCL-2/BCL-xL together, but not BCL-2 alone. PMID: 27852038 [PubMed - as supplied by publisher]

Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles. PLoS One. 2016;11(11):e0166178 Authors: Nadeem Aslam M, Bassis CM, Zhang L, Zaidi S, Varani J, Bergin IL Abstract A high-fat "Western-style" diet (HFWD) promotes obesity-related conditions including non-alcoholic steatohepatitis (NASH), the histologic manifestation of non-alcoholic fatty liver disease (NAFLD). In addition to high saturated fat and processed carbohydrates, the typical HFWD is deficient in calcium. Calcium-deficiency is an independent risk factor for many conditions associated with the Western-style diet. However, calcium has not been widely evaluated in the context of NAFLD. The goal of the present study was to determine if dietary calcium supplementation could protect mice fed a HFWD from NAFLD, specifically by decreasing non-alcoholic steatohepatitis (NASH) and its down-stream consequences. Male C57BL/6NCrl mice were maintained for 18-months on a HFWD containing dietary calcium at either 0.41 gm/kg feed (unsupplemented) or 5.25 gm/kg feed (supplemented). Although there was no difference in body weight or steatosis, calcium-supplemented mice were protected against downstream consequences of hepatic steatosis, manifested by lower inflammation, less fibrosis, and by lower overall histologic NAFLD activity scores (NAS). Calcium supplementation correlated with distinctly segregating gut fecal and cecal microbial communities as defined by 16S rRNA gene sequence. Further, calcium supplementation also correlated with decreased hepatic concentration of the major conjugated murine primary bile acid, tauro-β-muricholic acid (as well as a decrease in the parent unconjugated bile acid). Thus, calcium was protective against progression of diet-induced hepatic steatosis to NASH and end-stage liver disease, suggesting that calcium supplementation may effectively protect against adverse hepatic consequences of HFWD in cases where overall diet modification cannot be sustained. This protective effect occurred in concert with calcium-mediated gut microbial community shifts and alterations of the hepatic bile acid pool. PMID: 27851786 [PubMed - in process]

1005: EXAMINING ARDS ENDOTYPES USING SERUM METABOLOMICS. Crit Care Med. 2016 Dec;44(12 Suppl 1):327 Authors: Winston B, Donnelly S, Banoei M, Samra S, Mourad A, Vogel H, Fiehn O, C Canadian Critical Care Translational Biology Group PMID: 27850643 [PubMed - in process]

Metabolomic approach in probing drug candidates. Curr Top Med Chem. 2016 Nov 16; Authors: Liu C, D Alessandro A, Xia Y Abstract Metabolomics is the comprehensive characterization of endogenous small molecules metabolites, xenometabolites and their metabolisms. The recent introduction of high-throughput metabolomics approaches has fostered strides related to the capacity to in silico elaborate metabolomics data by means of system biology. Recent progresses in bioanalytical technologies assisted with algorithms enabling large-scale data analysis potentiate application of metabolomics approaches in biomarker-based disease diagnosis, therapeutic target identification, personalized medicine, and the monitoring of clinical outcomes. In this review article we will focus on recent applications of metabolomics approaches in the identification of potential therapeutic candidates based on our and others' confirmed experience with this cutting-edge technology. PMID: 27848895 [PubMed - as supplied by publisher]

Related Articles Metabolomics of Ulva lactuca Linnaeus (Chlorophyta) exposed to oil fuels: Fourier transform infrared spectroscopy and multivariate analysis as tools for metabolic fingerprint. Mar Pollut Bull. 2016 Nov 12;: Authors: Pilatti FK, Ramlov F, Schmidt EC, Costa C, Oliveira ER, Bauer CM, Rocha M, Bouzon ZL, Maraschin M Abstract Fossil fuels, e.g. gasoline and diesel oil, account for substantial share of the pollution that affects marine ecosystems. Environmental metabolomics is an emerging field that may help unravel the effect of these xenobiotics on seaweeds and provide methodologies for biomonitoring coastal ecosystems. In the present study, FTIR and multivariate analysis were used to discriminate metabolic profiles of Ulva lactuca after in vitro exposure to diesel oil and gasoline, in combinations of concentrations (0.001%, 0.01%, 0.1%, and 1.0% - v/v) and times of exposure (30min, 1h, 12h, and 24h). PCA and HCA performed on entire mid-infrared spectral window were able to discriminate diesel oil-exposed thalli from the gasoline-exposed ones. HCA performed on spectral window related to the protein absorbance (1700-1500cm(-1)) enabled the best discrimination between gasoline-exposed samples regarding the time of exposure, and between diesel oil-exposed samples according to the concentration. The results indicate that the combination of FTIR with multivariate analysis is a simple and efficient methodology for metabolic profiling with potential use for biomonitoring strategies. PMID: 27847170 [PubMed - as supplied by publisher]

Related Articles Untargeted metabolomics unravels functionalities of phosphorylation sites in Saccharomyces cerevisiae. BMC Syst Biol. 2016 Nov 15;10(1):104 Authors: Raguz Nakic Z, Seisenbacher G, Posas F, Sauer U Abstract BACKGROUND: Coordinated through a complex network of kinases and phosphatases, protein phosphorylation regulates essentially all cellular processes in eukaryotes. Recent advances in proteomics enable detection of thousands of phosphorylation sites (phosphosites) in single experiments. However, functionality of the vast majority of these sites remains unclear and we lack suitable approaches to evaluate functional relevance at a pace that matches their detection. RESULTS: Here, we assess functionality of 26 phosphosites by introducing phosphodeletion and phosphomimic mutations in 25 metabolic enzymes and regulators from the TOR and HOG signaling pathway in Saccharomyces cerevisiae by phenotypic analysis and untargeted metabolomics. We show that metabolomics largely outperforms growth analysis and recovers 10 out of the 13 previously characterized phosphosites and suggests functionality for several novel sites, including S79 on the TOR regulatory protein Tip41. We analyze metabolic profiles to identify consequences underlying regulatory phosphorylation events and detecting glycerol metabolism to have a so far unknown influence on arginine metabolism via phosphoregulation of the glycerol dehydrogenases. Further, we also find S508 in the MAPKK Pbs2 as a potential link for cross-talking between HOG signaling and the cell wall integrity pathway. CONCLUSIONS: We demonstrate that metabolic profiles can be exploited for gaining insight into regulatory consequences and biological roles of phosphosites. Altogether, untargeted metabolomics is a fast, sensitive and informative approach appropriate for future large-scale functional analyses of phosphosites. PMID: 27846849 [PubMed - in process]

Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis. Transl Psychiatry. 2016 Nov 15;6(11):e951 Authors: Suvitaival T, Mantere O, Kieseppä T, Mattila I, Pöhö P, Hyötyläinen T, Suvisaari J, Orešič M Abstract Psychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. In this study, we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients. We applied comprehensive metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. While corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline, that is, lipids known to be associated with increased liver fat. Our study suggests that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain. PMID: 27845774 [PubMed - in process]

Analysis of Serum Metabolites to Diagnose Bicuspid Aortic Valve. Sci Rep. 2016 Nov 15;6:37023 Authors: Wang W, Maimaiti A, Zhao Y, Zhang L, Tao H, Nian H, Xia L, Kong B, Wang C, Liu M, Wei L Abstract Bicuspid aortic valve (BAV) is the most common congenital heart disease. The current study aims to construct a diagnostic model based on metabolic profiling as a non-invasive tool for BAV screening. Blood serum samples were prepared from an estimation group and a validation group, each consisting of 30 BAV patients and 20 healthy individuals, and analyzed by liquid chromatography-mass spectrometry (LC-MS). In total, 2213 metabolites were detected and 41 were considered different. A model for predicting BAV in the estimation group was constructed using the concentration levels of monoglyceride (MG) (18:2) and glycerophospho-N-oleoyl ethanolamine (GNOE). A novel model named Zhongshan (ZS) was developed to amplify the association between BAV and the two metabolites. The area under curve (AUC) of ZS for BAV prediction was 0.900 (0.782-0.967) and was superior to all single-metabolite models when applied to the estimation group. Using optimized cutoff (-0.1634), ZS model had a sensitivity score of 76.7%, specificity score of 90.0%, positive predictive value of 80% and negative predictive value of 85.0% for the validation group. These results support the use of serum-based metabolomics profiling method as a complementary tool for BAV screening in large populations. PMID: 27845433 [PubMed - in process]