PubMed

Related Articles In Situ Metabolomics in Cancer by Mass Spectrometry Imaging. Adv Cancer Res. 2017;134:117-132 Authors: Buck A, Aichler M, Huber K, Walch A Abstract Metabolomics is a rapidly evolving and a promising research field with the expectation to improve diagnosis, therapeutic treatment prediction, and prognosis of particular diseases. Among all techniques used to assess the metabolome in biological systems, mass spectrometry imaging is the method of choice to qualitatively and quantitatively analyze metabolite distribution in tissues with a high spatial resolution, thus providing molecular data in relation to cancer histopathology. The technique is ideally suited to study tissues molecular content and is able to provide molecular biomarkers or specific mass signatures which can be used in classification or the prognostic evaluation of tumors. Recently, it was shown that FFPE tissue samples are also suitable for metabolic analyses. This progress in methodology allows access to a highly valuable resource of tissues believed to widen and strengthen metabolic discovery-driven studies. PMID: 28110648 [PubMed - in process]

Related Articles Insomnia does not mediate or modify the association between MTNR1B risk variant rs10830963 and glucose levels. Diabetologia. 2016 May;59(5):1070-2 Authors: Ollila HM, Kronholm E, Kettunen J, Silander K, Perola M, Porkka-Heiskanen T, Salomaa V, Paunio T PMID: 26912228 [PubMed - indexed for MEDLINE]

Related Articles Acute-on-chronic liver failure: recent update. J Biomed Res. 2017 Jan 19;: Authors: Azeem A, Ka CS, Daqing M Abstract Acute on chronic liver failure (ACLF) was first described in 1995 as a clinical syndrome distinct to classic acute decompensation. Characterized by complications of decompensation, ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between 45% and 90%. Despite the clinical relevance of the condition, it still remains largely undefined with continued disagreement regarding its precise etiological factors, clinical course, prognostic criteria and management pathways. It is concerning that, despite our relative lack of understanding of the condition, the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%. This paper highlights our current understanding of ACLF, including its etiology, diagnostic and prognostic criteria and pathophysiology. It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates. The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters, while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF. PMID: 28110320 [PubMed - as supplied by publisher]

Related Articles Metabolic and physiological adjustment of Suaeda maritima to combined salinity and hypoxia. Ann Bot. 2017 Jan 20;: Authors: Behr JH, Bouchereau A, Berardocco S, Seal CE, Flowers TJ, Zörb C Abstract BACKGROUND AND AIMS: Suaeda maritima is a halophyte commonly found on coastal wetlands in the intertidal zone. Due to its habitat S. maritima has evolved tolerance to high salt concentrations and hypoxic conditions in the soil caused by periodic flooding. In the present work, the adaptive mechanisms of S. maritima to salinity combined with hypoxia were investigated on a physiological and metabolic level. METHODS: To compare the adaptive mechanisms to deficient, optimal and stressful salt concentrations, S. maritima plants were grown in a hydroponic culture under low, medium and high salt concentrations. Additionally, hypoxic conditions were applied to investigate the impact of hypoxia combined with different salt concentrations. A non-targeted metabolic approach was used to clarify the biochemical pathways underlying the metabolic and physiological adaptation mechanisms of S. maritima KEY RESULTS: Roots exposed to hypoxic conditions showed an increased level of tricarboxylic acid (TCA)-cycle intermediates such as succinate, malate and citrate. During hypoxia, the concentration of free amino acids increased in shoots and roots. Osmoprotectants such as proline and glycine betaine increased in concentrations as the external salinity was increased under hypoxic conditions. CONCLUSIONS: The combination of high salinity and hypoxia caused an ionic imbalance and an increase of metabolites associated with osmotic stress and photorespiration, indicating a severe physiological and metabolic response under these conditions. Disturbed proline degradation in the roots induced an enhanced proline accumulation under hypoxia. The enhanced alanine fermentation combined with a partial flux of the TCA cycle might contribute to the tolerance of S. maritima to hypoxic conditions. PMID: 28110268 [PubMed - as supplied by publisher]

Related Articles Salecan protected against concanavalin A-induced acute liver injury by modulating T cell immune responses and NMR-based metabolic profiles. Toxicol Appl Pharmacol. 2017 Jan 18;: Authors: Sun Q, Xu X, Yang X, Weng D, Wang J, Zhang J Abstract Salecan, a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, has been reported to exhibit a wide range of biological effects. The aims of the present study were to investigate the protective effect of salecan against Concanavalin A (ConA)-induced hepatitis, a well-established animal model of immune-mediated liver injury, and to search for possible mechanisms. C57BL/6 mice were pretreated with salecan followed by ConA injection. Salecan treatment significantly reduced ConA-induced acute liver injury, and suppressed the expression and secretion of inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-6 and IL-1β in ConA-induced liver injury model. The high expression levels of chemokines and adhesion molecules such as MIP-1α, MIP-1β, ICAM-1, MCP-1 and RANTES in the liver induced by ConA were also down-regulated after salecan treatment. Salecan inhibited the infiltration and activation of inflammatory cells, especially T cells, in the liver induced by ConA. Moreover, salecan reversed the metabolic profiles of ConA-treated mice towards the control group by partly recovering the metabolic perturbations induced by ConA. Our results suggest the preventive and therapeutic potential of salecan in immune-mediated hepatitis. PMID: 28109817 [PubMed - as supplied by publisher]

Related Articles Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype. Mol Cancer Res. 2017 Jan 20;: 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: noninvasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wnt(liver)) 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-Wnt(liver) 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 β-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-Wnt(liver) 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. Mol Cancer Res; 15(2); 1-12. ©2016 AACR. PMID: 28108628 [PubMed - as supplied by publisher]

Related Articles Metabolomic study of the intervention effects of Shuihonghuazi Formula, a Traditional Chinese Medicinal formulae, on hepatocellular carcinoma (HCC) rats using performance HPLC/ESI-TOF-MS. J Ethnopharmacol. 2017 Jan 17;: Authors: Bao Y, Wang S, Yang X, Tianjiao L, Xia M, Meng X Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system in a holistic context, and its property consists with the global view of Traditional Chinese Medicine (TCM). Shuihonghuazi Formula (SHHZF) has been used for liver cancer early treatment in clinical for more than thirty years, but its mechanism remains unclear completely. This paper was designed to explore the therapeutic effects of SHHZF on liver cancer and its metabolomic characters. MATERIALS AND METHODS: All the rats were given diethylnitrosamine (DEN) at the dosage of 70mg/kg for 14 weeks. From the 7th weeks, SHHZF was given to the rats which lasted for 10 weeks. Therapeutic effects of SHHZF was compared with that of cyclophosphamide (CTX). High performance liquid-chromatography/electrospray-ionization time of flight mass spectrometer (HPLC/ESI-TOF-MS) combined with pattern recognition approaches including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), was integrated to approximate the comprehensive metabolic signature and discover differentiating metabolites by Agilent MPP 12.1. The changes in metabolic profiling in plasma were restored to their baseline values after SHHZF treatment according to the PLS-DA score plots. RESULTS: The results indicated that 23ions as "differentiating metabolites". The alterations in those metabolites were associated with perturbations in fatty acid and bile acid metabolism, in response to liver cancer through immune and nervous system. And SHHZF could increase the uptake and utilization of linoleic acid and oleic acid, increase arachidonic acid-like substance content and enhance organism immunity of liver cancer rats. And it also could increase the translation from phosphatidylethanolamine (PE) to Phosphatidylcholine (PC), linoleic acid metabolism and inhibits abnormal metabolism of bile acid. CONCLUSIONS: The mechanism of therapeutic effects of SHHZF on liver cancer by adjusting the activities of PE N-methyl transferase (PEMT), Lysophospholipase D, methylenetetrahydrofolate ruductase (MTHFR) and ysophospholipase was elucidated by the method of metabonomics for the first time. PMID: 28108381 [PubMed - as supplied by publisher]

Related Articles Development of data-independent acquisition workflows for metabolomic analysis on a quadrupole-orbitrap platform. Talanta. 2017 Mar 01;164:128-136 Authors: Zhou J, Li Y, Chen X, Zhong L, Yin Y Abstract Untargeted metabolomic profiling has been widely used in recent years. However, the low reproducibility of the data-dependent acquisition (DDA) strategy presents a major bottleneck that considerably limits the reliability of metabolomic studies in biological and clinical research. The data-independent acquisition (DIA) strategy is proposed to solve the above-mentioned problem, and it is gaining popularity. This paper presents a novel approach for performing metabolomic analysis using an untargeted, liquid chromatography-data independent-mass spectrometry (LC-DIA-MS) strategy on a quadrupole-Orbitrap platform. Using chemical standards and metabolites extracted from serum samples, we optimized the LC-DIA-MS parameters to analyze hydrophilic metabolites and lipids. The quantitative performance and analytical reliability were evaluated, and the performances of DIA, DDA, and all-ion fragmentation mode were compared. Finally, as a proof of concept, we applied the constructed DIA workflow to a comparative metabolomic study of papillary thyroid carcinoma (TC) serum samples. Several metabolites, including carnitine, trimethylamine N-oxide, and some amino acids, significantly changed between patients and healthy controls. This study demonstrated the feasibility and advantage of the DIA strategy on untargeted metabolomic analysis for biological study and clinical biomarker screening. PMID: 28107906 [PubMed - in process]

Related Articles In vivo metabolomic interpretation of the anti-obesity effects of hyacinth bean (Dolichos lablab L.) administration in high-fat diet mice. Mol Nutr Food Res. 2017 Jan 20;: Authors: Suh DH, Lee HW, Jung ES, Singh D, Kim SH, Lee CH Abstract SCOPE: The esoteric anti-obesity effects of hyacinth bean (Dolichos lablab L) have largely remained unexplored. Herein, we investigated the anti-obesity mechanisms of hyacinth bean compared to milk thistle, a natural herb employed for ameliorating obesity-related diseases, using high fat-diet (HFD) fed mice towards unfolding the perplexing mechanisms. METHODS AND RESULTS: C57BL/6J mice were orally administered hyacinth bean (25 mg/kg/day) and milk thistle (100 mg/kg/day) for 9 weeks along with HFD. Intriguingly, a number of anti-obesity mechanisms indexed through clinical parameters, suppression in weight gains and liver steatosis were found similar with some disparity. Further, the corresponding metabolic implications were studied through MS-based metabolite profiling, and using the Kyoto Encyclopedia of Genes and Genomes (KEGG) for metabolic pathways revealing that hyacinth bean or milk thistle administration effectively attenuates the HFD induced lipid, glucose, and bile acid metabolism, with former specifically attenuates pyruvate derived amino acids metabolism. Among them, valine, asparagine, and lysine displayed high correlation with blood clinical parameters. CONCLUSION: A lower dose of hyacinth bean resulted in similar anti-obesity effects as milk thistle, as confirmed by both clinical and metabolomics analyses. Equivocally, we conjecture that hyacinth bean could be used as a potent anti-obesity herbal functional food. This article is protected by copyright. All rights reserved. PMID: 28106337 [PubMed - as supplied by publisher]

Related Articles Recent Advances in NMR-Based Metabolomics. Anal Chem. 2017 Jan 03;89(1):490-510 Authors: Nagana Gowda GA, Raftery D PMID: 28105846 [PubMed - in process]

Related Articles Disease monitoring of hepatocellular carcinoma through metabolomics. World J Hepatol. 2017 Jan 08;9(1):1-17 Authors: Fitian AI, Cabrera R Abstract We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included "HCC", "metabolomics", "metabolomics", "metabonomic" and "biomarkers". We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables. Where reported, we also extracted and summarized the metabolites and pathways most highly associated with the development of cirrhosis in table format. Pathways of lysophospholipid, sphingolipid, bile acid, amino acid, and reactive oxygen species metabolism were most consistently associated with HCC in the cited works. Several studies also elucidate metabolic alterations strongly associated with cirrhosis, with γ-glutamyl peptides, bile acids, and dicarboxylic acids exhibiting the highest capacity for stratifying cirrhosis patients from appropriately matched controls. Collectively, global metabolomic profiles of the referenced works exhibit a promising diagnostic capacity for HCC at a capacity greater than that of conventional diagnostic biomarker alpha-fetoprotein. Metabolomics is a powerful strategy for identifying global metabolic signatures that exhibit potential to be leveraged toward the screening, diagnosis, and management of HCC. A streamlined study design and patient matching methodology may improve concordance among metabolomic datasets in future works. PMID: 28105254 [PubMed - in process]

Related Articles Exposure to high levels of fumarate and succinate leads to apoptotic cytotoxicity and altered global DNA methylation profiles in vitro. Biochimie. 2017 Jan 16;: Authors: Wentzel JF, Lewies A, Bronkhorst AJ, van Dyk E, du Plessis LH, Pretorius PJ Abstract In the Krebs cycle, succinate is oxidized to fumarate by succinate dehydrogenase (SDH), followed by the conversion of fumarate to malate by fumarate hydratase (FH). In cells with defective SDH and FH, the Krebs cycle is congested, respiration impaired and fumarate and succinate accumulates. Several studies have indicated that the accumulation of these substrates are associated with cytotoxicity and oncogenesis. High levels of succinate and fumarate induce hypoxia inducible factor (HIF1A) hydroxylases, leading to the activation of oncogenic HIF pathways. However, the role of HIF as primary inducer of oncogenic change has been questioned, as other non-enzymatic mechanisms have been shown to interfere with cellular metabolism, cell signalling as well as disrupting protein function. Owing to the essential roles that SDH and FH play in cellular energy metabolism, and their associated tumor suppressor capacity, it is vital to understand the biochemical effects resulting from the accumulation of their associated metabolites. Therefore, in this study, we investigated the effect of high concentrations of succinate and fumarate exposure on cell viability, genome integrity and global DNA methylation using a human hepatocellular carcinoma (HepG2) cell culture model. It was found that relatively high concentrations of succinate and fumarate cause a loss of cell viability, which seems to be orchestrated through an apoptotic pathway. Cells exposed to high levels of succinate also presented with elevated caspase 3 and/or caspase 7 levels. In addition, elevated levels of fumarate lead to extensive DNA fragmentation, which may contribute pathophysiologically by inducing chromosomal instability, while succinate demonstrated lower genotoxicity. Furthermore, both succinate and fumarate altered the global DNA methylation patterns via significant DNA hypermethylation. Since numerous studies have reported correlations between aberrant DNA methylation and oncogenesis, hypermethylation may contribute to the oncogenesis observed in cells exposed to high concentrations of these metabolites. PMID: 28104508 [PubMed - as supplied by publisher]

Related Articles Urinary 6β-Hydroxycortisol/Cortisol Ratio Most Highly Correlates With Midazolam Clearance Under Hepatic CYP3A Inhibition and Induction in Females: A Pharmacometabolomics Approach. AAPS J. 2016 09;18(5):1254-61 Authors: Shin KH, Ahn LY, Choi MH, Moon JY, Lee J, Jang IJ, Yu KS, Cho JY Abstract Endogenous metabolites of cytochrome P450 (CYP3A) are useful in predicting drug-drug interactions between in vivo CYP3A inhibitors and inducers for clinical applications of CYP3A substrate drugs. This study aimed to develop predictable markers of the magnitude of hepatic CYP3A induction and inhibition in healthy female subjects using pharmacometabolomics. Twelve female subjects received midazolam during three study phases: 1 mg midazolam (control phase), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). Throughout the study, blood samples were collected 24 h after midazolam administration and urine samples at 12-h intervals during the 24 h before and after midazolam administration for the analysis of endogenous steroid metabolites. A statistical model was generated to predict midazolam clearance using measurements of endogenous metabolites associated with the inhibition and induction of CYP3A. Mean midazolam clearance decreased to ∼20% of control levels during the inhibition phase and increased more than 2-fold during the induction phase. Of the urine and plasma metabolites measured, the 6β-hydroxycortisol/cortisol ratio was most significantly correlated with midazolam clearance during hepatic CYP3A inhibition and induction. Our results suggest that the urinary 6β-hydroxycortisol/cortisol ratio is the best predictor of hepatic CYP3A activity under both maximal inhibition and maximal induction. Furthermore, the predictive model including 6β-hydroxycortisol/cortisol as a covariate could be applied to predict the magnitude of CYP3A-mediated drug interactions. PMID: 27317471 [PubMed - indexed for MEDLINE]

Involvement of autophagy in NK cell development and function. Autophagy. 2017 Jan 19;:0 Authors: López-Soto A, Bravo-San Pedro JM, Kroemer G, Galluzzi L, Gonzalez S Abstract Natural killer (NK) cells are the prototypical members of the recently identified family of innate lymphoid cells (ILCs). Thanks to their cytotoxic and secretory functions, NK cells play a key role in the immune response to cells experiencing various forms of stress, including viral infection and malignant transformation. Autophagy is a highly conserved network of degradative pathways that participate in the maintenance of cellular and organismal homeostasis as they promote adaptation to adverse microenvironmental conditions. The relevance of autophagy in the development and functionality of cellular components of the adaptive immune system is well established. Conversely, whether autophagy also plays an important role in the biology of ILC populations such as NK cells has long remained elusive. Recent experimental evidence shows that ablating Atg5 (autophagy related 5, an essential component of the autophagic machinery) in NK cells and other specific ILC populations results in progressive mitochondrial damage, reactive oxygen species (ROS) overgeneration, and regulated cell death, hence interrupting ILC development. Moreover, disrupting the interaction of ATG7 with phosphorylated FOXO1 (forkhead box O1) in the cytosol of immature NK cells prevents autophagic responses that are essential for NK cell maturation. These findings suggest that activating autophagy may support the maturation of NK cells and other ILCs that manifest antiviral and anticancer activity. PMID: 28103115 [PubMed - as supplied by publisher]

Comparing Early Liver Graft Function From Heart Beating and Living-Donors: A Pilot Study Aiming to Identify New Biomarkers of Liver Injury. Biopharm Drug Dispos. 2017 Jan 19;: Authors: Yang QJ, Kluger M, Goryński K, Pawliszyn J, Bojko B, Yu AM, Noh K, Selzner M, Jerath A, McCluskey S, Sandy Pang K, Wąsowicz M Abstract Liver and kidney functions among recipients of liver transplantation (LT) surgery with heart beating (HBD, n = 13) or living donors (LD, n = 9) with different cold ischemic times were examined during the neohepatic phase for clearing rocuronium bromide (ROC, cleared by liver and kidney) and tranexamic acid (TXA, cleared by kidney). Solid phase micro-extraction and LC-MS/MS was applied to determine the plasma concentrations of ROC and TXA, and creatinine was determined by standard laboratory methods. Metabolomics and the relative expressions of miRNA122, miRNA148a, and γ-glutamyltranspeptidase (GGT), liver injury biomarkers, were also measured. ROC clearance for HBD was significantly lower than that for LD (0.147 ± 0.052 vs. 0.265 ± 0.148 mL · min(-1)  · g(-1) liver) after intravenous injection (0.6 mg · kg(-1) ). Clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg · kg(-1)  · h(-1) ), was similar between HBD and LD (~1 mL · min(-1)  · kg(-1) ). Metabolomics data revealed higher bile acids, phospholipids, and lipid ω-oxidation metabolite clusters for HBD. miR122 and miR148a expressions were similar for HBD and LD whereas GGT expression was significantly increased for HBD. TXA clearance in both groups was lower than GFR, showing a small extent of hepatorenal coupling. CONCLUSIONS: ROC clearance was reduced and GGT were higher in the HBD group of longer cold ischemic times, and HBD patients performed worse than the LD group during the neophase. The HBD group further showed higher clusters of bile acids, phospholipids and lipid ω-oxidation products, suggesting that these, ROC CL and GGT expression could serve as sensitive indices of early graft function. PMID: 28102538 [PubMed - as supplied by publisher]

Related Articles Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression. Prostate. 2017 Jan 19;: Authors: Kratochvilova M, Raudenska M, Heger Z, Richtera L, Cernei N, Adam V, Babula P, Novakova M, Masarik M, Gumulec J Abstract BACKGROUND: Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed. METHODS: Amino acid profiles were examined using an ion-exchange liquid chromatography. Intracellular zinc content was measured by atomic absorption spectrometry. Metallothionein was quantified using differential pulse voltammetry. The content of reduced glutathione was determined using high performance liquid chromatography coupled with an electrochemical detector. Cellular antioxidant capacity was determined by the ABTS test and gene expression analysis was performed by qRT-PCR. RESULTS AND CONCLUSIONS: Long-term zinc treatment was shown to reroute cell metabolism from benign to more malignant type. Long-term application of high concentration of zinc(II) significantly enhanced cisplatin resistance, invasiveness, cellular antioxidant capacity, synthesis of glutathione, and expression of treatment resistance- and stemness-associated genes (SOX2, POU5F1, BIRC5). Tumorous cell lines universally displayed high accumulation of aspartate and sarcosine and depletion of essential amino acids. Increased aspartate/threonine, aspartate/methionine, and sarcosine/serine ratios were associated with cancer phenotype with high levels of sensitivity and specificity. Prostate © 2017 Wiley Periodicals, Inc. PMID: 28101932 [PubMed - as supplied by publisher]

Related Articles Effect of timing of collection of salivary metabolomic biomarkers on oral cancer detection. Amino Acids. 2017 Jan 18;: Authors: Ishikawa S, Sugimoto M, Kitabatake K, Tu M, Sugano A, Yamamori I, Iba A, Yusa K, Kaneko M, Ota S, Hiwatari K, Enomoto A, Masaru T, Iino M Abstract The aim of this study is to evaluate the effect of duration after meals for saliva collections for oral cancer detection using metabolomics. Saliva samples were collected from oral cancer patients (n = 22) and controls (n = 44). Saliva from cancer patients was collected 12 h after dinner, and 1.5 and 3.5 h after breakfast. Control subjects fasted >1.5 h prior to saliva collection. Hydrophilic metabolites were analyzed using capillary electrophoresis mass spectrometry. Levels of 51 metabolites differed significantly in controls vs. oral cancer patients at the 12-h fasting time point (P < 0.05). Fifteen and ten metabolites differed significantly at the 1.5- and 3.5-h time points, respectively. The area of under receiver operating characteristic curve for discriminating oral cancer patients from controls was greatest at the 12-h fasting time point. The collection time after meals affects levels of salivary metabolites for oral cancer screening. The 12-h fasting after dinner time point is optimal. This study contributes to design of saliva collection protocols for metabolomics-based biomarker discovery. PMID: 28101653 [PubMed - as supplied by publisher]

Related Articles Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics. Amino Acids. 2017 Jan 18;: Authors: Mu C, Yang Y, Yu K, Yu M, Zhang C, Su Y, Zhu W Abstract In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P < 0.05) the concentration of urea. Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P < 0.05) the concentrations of propionate and butyrate in the feces. Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P < 0.05) in the large intestine of antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets. PMID: 28101652 [PubMed - as supplied by publisher]

Related Articles Effect of Metformin on Metabolites and Relation With Myocardial Infarct Size and Left Ventricular Ejection Fraction After Myocardial Infarction. Circ Cardiovasc Genet. 2017 Feb;10(1): Authors: Eppinga RN, Kofink D, Dullaart RP, Dalmeijer GW, Lipsic E, van Veldhuisen DJ, van der Horst IC, Asselbergs FW, van der Harst P Abstract BACKGROUND: Left ventricular ejection fraction (LVEF) and infarct size (ISZ) are key predictors of long-term survival after myocardial infarction (MI). However, little is known about the biochemical pathways driving LV dysfunction after MI. To identify novel biomarkers predicting post-MI LVEF and ISZ, we performed metabolic profiling in the GIPS-III randomized clinical trial (Glycometabolic Intervention as Adjunct to Primary Percutaneous Intervention in ST Elevation Myocardial Infarction). We also investigated the metabolic footprint of metformin, a drug associated with improved post-MI LV function in experimental studies. METHODS AND RESULTS: Participants were patients with ST-segment-elevated MI who were randomly assigned to receive metformin or placebo for 4 months. Blood samples were obtained on admission, 24 hours post-MI, and 4 months post-MI. A total of 233 metabolite measures were quantified using nuclear magnetic resonance spectrometry. LVEF and ISZ were assessed 4 months post-MI. Twenty-four hours post-MI measurements of high-density lipoprotein (HDL) triglycerides (HDL-TG) predicted LVEF (β=1.90 [95% confidence interval (CI), 0.82 to 2.98]; P=6.4×10(-4)) and ISZ (β=-0.41 [95% CI, -0.60 to -0.21]; P=3.2×10(-5)). In addition, 24 hours post-MI measurements of medium HDL-TG (β=-0.40 [95% CI, -0.60 to -0.20]; P=6.4×2×10(-5)), small HDL-TG (β=-0.34 [95% CI, -0.53 to -0.14]; P=7.3×10(-4)), and the triglyceride content of very large HDL (β=-0.38 [95% CI, -0.58 to -0.18]; P=2.7×10(-4)) were associated with ISZ. After the 4-month treatment, the phospholipid content of very large HDL was lower in metformin than in placebo-treated patients (28.89% versus 38.79%; P=7.5×10(-5)); alanine levels were higher in the metformin group (0.46 versus 0.44 mmol/L; P=2.4×10(-4)). CONCLUSIONS: HDL triglyceride concentrations predict post-MI LVEF and ISZ. Metformin increases alanine levels and reduces the phospholipid content in very large HDL particles. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT01217307. Unique Identifier: NCT01217307. PMID: 28100626 [PubMed - in process]

Related Articles The nutritional metabolomics crossroads: how to ensure success for dietary biomarkers. Am J Clin Nutr. 2017 Jan 18;: Authors: Brennan L PMID: 28100510 [PubMed - as supplied by publisher]