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Sample records for metabolomics identified oral

  1. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond.

    Science.gov (United States)

    Washio, Jumpei; Takahashi, Nobuhiro

    2016-06-02

    Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  2. Serum metabolomics in oral leukoplakia and oral squamous cell carcinoma.

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    Sridharan, Gokul; Ramani, Pratibha; Patankar, Sangeeta

    2017-01-01

    Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is composed of diverse group of metabolites, can aid in diagnosis and prognosis of oral squamous cell carcinoma (OSCC). The aim of the present study is to analyze and identify serum metabolites in oral leukoplakia and OSCC as a potential diagnostic biomarker and a predictor for malignant transformation of oral leukoplakia. Serum metabolomic profile of patients diagnosed with oral leukoplakia (n = 21) and OSCC (n = 22) was compared with normal controls (n = 18) using quadrupole time of flight-liquid chromatography-mass spectrometry. MassHunter profile software was used for metabolite identification, and statistical analysis to assess the variation of the metabolites was performed using Mass Profiler Professional software. Statistical significance between the three groups was expressed using ANOVA (P oral leukoplakia and OSCC than in normal controls. Furthermore, significant upregulation of 5,6-dihydrouridine, 4-hydroxypenbutolol glucuronide, 8-hydroxyadenine, and putrescine was evident in OSCC group than in oral leukoplakia. Upregulation of L-carnitine, lysine, 2-methylcitric acid, putrescine; 8-hydroxyadenine; 17-estradiol; 5,6-dihydrouridine; and MTA suggests their diagnostic potential in oral leukoplakia and OSCC. Further, a significant upregulation of putrescine, 8-hydroxyadenine, and 5,6-dihydrouridine in OSCC than in oral leukoplakia indicates their potential role in predicting the malignant transformation of oral leukoplakia.

  3. Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma

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    Pranab K. Mukherjee

    2017-06-01

    Conclusions: Oral metabolites related to energy metabolism were elevated in HNSCC, and acylcarnitine and 2HG may have potential as non-invasive biomarkers. Further validation in clinical studies is warranted.

  4. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

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    Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

    2014-01-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

  5. Metabolomic analysis of the saliva of Japanese patients with oral squamous cell carcinoma.

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    Ohshima, Mitsuyoshi; Sugahara, Keisuke; Kasahara, Kiyohiro; Katakura, Akira

    2017-05-01

    The aim of the present study was to characterize the metabolic systems in Japanese patients with oral squamous cell carcinoma (OSCC) using capillary electrophoresis-mass spectrometry (CE-MS) metabolome analysis of saliva samples. A previous study showed variations among ethnicities and tumor sites in the saliva metabolome of patients with OSCC using CE-MS. In the present study, saliva was obtained from 22 Japanese patients with OSCC and from 21 healthy controls who visited the Department of Dentistry, Oral and Maxillofacial Surgery, Tokyo Dental Collage Ichikawa General Hospital, Tokyo, Japan, and all samples were subject to comprehensive quantitative metabolome analysis using CE-MS. A total of 499 metabolites were detected as CE-MS peaks in the saliva tested from the two groups. A total of 25 metabolites were revealed as potential markers to discriminate between patients with OSCC and healthy controls: Choline, p-hydroxyphenylacetic acid, and 2-hydroxy-4-methylvaleric acid (P<0.001); valine, 3-phenyllactic acid, leucine, hexanoic acid, octanoic acid, terephthalic acid, γ-butyrobetaine, and 3-(4-hydroxyphenyl)propionic acid (P<0.01); and isoleucine, tryptophan, 3-phenylpropionic acid, 2-hydroxyvaleric acid, butyric acid, cadaverine, 2-oxoisovaleric acid, N6,N6,N6-trimethyllysine, taurine, glycolic acid, 3-hydroxybutyric acid, heptanoic acid, alanine, and urea (P<0.05, according to the Wilcoxon rank sum test). A previous study by Sugimoto and co-workers detected 24 discriminatory metabolites, 7 of which (taurine, valine, leucine, isoleucine, choline, cadaverine, and tryptophan) were also detected in the present study. In the present study, however, choline, metabolites in the branched chain amino acids (BCAA) cycle, urea, and 3-hydroxybutyric acid were also characterized. Choline and metabolites of the BCAA cycle have previously been reported in OSCC using metabolome analysis. To the best of our knowledge, no previous reports have identified urea and 3

  6. Metabolomics

    DEFF Research Database (Denmark)

    Pedersen, Hans

    is a presentation of a core consistency diagnostic aiding in determining the number of components in a PARAFAC2 model. It is of great importance to validate especially PLS-DA models and if not done properly, the developed models might reveal spurious groupings. Furthermore, data from metabolomics studies contain...... and the results indicate that GC-MS-based metabolomics in combination with PARAFAC2 modelling is applicable for extracting relevant biological information from the plasma samples. Overall, the work in this thesis shows that suitable and properly validated chemometrics models used in metabolomics are very useful...

  7. Metabolomics

    DEFF Research Database (Denmark)

    Kamstrup-Nielsen, Maja Hermann

    how to properly handle complex metabolomics data, in order to achieve reliable and valid multivariate models. This has been illustrated by three case studies with examples of forecasting breast cancer and early detection of colorectal cancer based on data from nuclear magnetic resonance (NMR...... based on NMR data with RRV and known risk markers. The sensitivity and specificity values are 0.80 and 0.79, respectively, for a test set validated model. The second case study is based on plasma samples with verified colorectal cancer and three types of control samples analysed by fluorescence...... spectroscopy a potential tool in early detection of colorectal cancer. Finally, plasma samples have been analysed using GC-MS. The method requires extensive sample preparation and therefore the study can only be considered a feasibility study with room for optimization. However, 14 plasma samples were analysed...

  8. Identifying biomarkers of dietary patterns by using metabolomics123

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    Derkach, Andriy; Reedy, Jill; Subar, Amy F; Sampson, Joshua N; Albanes, Demetrius; Gu, Fangyi; Kontto, Jukka; Lassale, Camille; Liao, Linda M; Männistö, Satu; Mondul, Alison M; Weinstein, Stephanie J; Irwin, Melinda L; Mayne, Susan T; Stolzenberg-Solomon, Rachael

    2017-01-01

    Background: Healthy dietary patterns that conform to national dietary guidelines are related to lower chronic disease incidence and longer life span. However, the precise mechanisms involved are unclear. Identifying biomarkers of dietary patterns may provide tools to validate diet quality measurement and determine underlying metabolic pathways influenced by diet quality. Objective: The objective of this study was to examine the correlation of 4 diet quality indexes [the Healthy Eating Index (HEI) 2010, the Alternate Mediterranean Diet Score (aMED), the WHO Healthy Diet Indicator (HDI), and the Baltic Sea Diet (BSD)] with serum metabolites. Design: We evaluated dietary patterns and metabolites in male Finnish smokers (n = 1336) from 5 nested case-control studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Participants completed a validated food-frequency questionnaire and provided a fasting serum sample before study randomization (1985–1988). Metabolites were measured with the use of mass spectrometry. We analyzed cross-sectional partial correlations of 1316 metabolites with 4 diet quality indexes, adjusting for age, body mass index, smoking, energy intake, education, and physical activity. We pooled estimates across studies with the use of fixed-effects meta-analysis with Bonferroni correction for multiple comparisons, and conducted metabolic pathway analyses. Results: The HEI-2010, aMED, HDI, and BSD were associated with 23, 46, 23, and 33 metabolites, respectively (17, 21, 11, and 10 metabolites, respectively, were chemically identified; r-range: −0.30 to 0.20; P = 6 × 10−15 to 8 × 10−6). Food-based diet indexes (HEI-2010, aMED, and BSD) were associated with metabolites correlated with most components used to score adherence (e.g., fruit, vegetables, whole grains, fish, and unsaturated fat). HDI correlated with metabolites related to polyunsaturated fat and fiber components, but not other macro- or micronutrients (e

  9. Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

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    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Severe AAH is characterized by a distinct metabolic phenotype spanning

  10. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

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    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  11. Metabolomic profiling to identify predictors of response to vitamin E for non-alcoholic steatohepatitis (NASH.

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    Jianfeng Cheng

    Full Text Available Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS. The current study utilized samples collected in the PIVENS trial to identify: (1 baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2 end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547 quantified by mass spectrometry was performed in vitamin E responders (n = 16, vitamin E non-responders (n = 15, and placebo responders (n = 15. At baseline, phenyl-propionic acid (Odds ratio: 29.4, p<0.01, indole-propionic acid levels (Odds ratio: 16.2, p<0.01 were directly associated with a subsequent histologic response to vitamin E treatment whereas γ-carboxyethylhydroxychroman (CEHC levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p<0.02 and gamma-glutamyl valine (Fold change: 0.8, p<0.03 were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement on treatment and support further studies to validate these biomarkers.

  12. Targeted Metabolomics Identifies Pharmacodynamic Biomarkers for BIO 300 Mitigation of Radiation-Induced Lung Injury.

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    Jones, Jace W; Jackson, Isabel L; Vujaskovic, Zeljko; Kaytor, Michael D; Kane, Maureen A

    2017-12-01

    Biomarkers serve a number of purposes during drug development including defining the natural history of injury/disease, serving as a secondary endpoint or trigger for intervention, and/or aiding in the selection of an effective dose in humans. BIO 300 is a patent-protected pharmaceutical formulation of nanoparticles of synthetic genistein being developed by Humanetics Corporation. The primary goal of this metabolomic discovery experiment was to identify biomarkers that correlate with radiation-induced lung injury and BIO 300 efficacy for mitigating tissue damage based upon the primary endpoint of survival. High-throughput targeted metabolomics of lung tissue from male C57L/J mice exposed to 12.5 Gy whole thorax lung irradiation, treated daily with 400 mg/kg BIO 300 for either 2 weeks or 6 weeks starting 24 h post radiation exposure, were assayed at 180 d post-radiation to identify potential biomarkers. A panel of lung metabolites that are responsive to radiation and able to distinguish an efficacious treatment schedule of BIO 300 from a non-efficacious treatment schedule in terms of 180 d survival were identified. These metabolites represent potential biomarkers that could be further validated for use in drug development of BIO 300 and in the translation of dose from animal to human.

  13. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

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    McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

    2013-04-01

    Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate ( p = 4.4 × 10 -5 , q = 0.013), tryptophan ( p = 7.0 × 10 -4 , q = 0.035) and 2-hydroxyglutarate ( p = 1.1 × 10 -4 , q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate ( p = 3.8 × 10 -7 ). Associations specific to repeated (5 day) MA exposure included phosphocholine ( p = 4.0 × 10 -4 , q = 0.087) and ergothioneine ( p = 3.0 × 10 -4 , q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

  14. Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

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    Kind, Tobias; Cho, Eunho; Park, Taeeun D.; Deng, Nan; Liu, Zhenqiu; Lee, Tack; Fiehn, Oliver; Kim, Jayoung

    2016-01-01

    This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms. PMID:27976711

  15. Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes.

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    O'Kell, Allison L; Garrett, Timothy J; Wasserfall, Clive; Atkinson, Mark A

    2017-08-25

    While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n = 6) and healthy (n = 6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of known and unknown metabolites. Random forest classification identified 5/6 dogs per group correctly with overall out of bag error rate = 16.7%. Diabetic dogs demonstrated significant upregulation of glycolysis/gluconeogenesis intermediates (e.g., glucose/fructose, C 6 H 12 O 6 , keto-hexose, deoxy-hexose, (P diabetic versus healthy dogs (P diabetic animals (P diabetic versus healthy dogs shared similarities with those reported in human T1D (e.g., alterations in glycolysis/gluconeogensis metabolites, bile acids, and elevated branched chain AA). Further studies are warranted to evaluate the utility of canine diabetes to provide novel mechanistic insights to the human disorder.

  16. Disruption of TCA Cycle and Glutamate Metabolism Identified by Metabolomics in an In Vitro Model of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Veyrat-Durebex, Charlotte; Corcia, Philippe; Piver, Eric; Devos, David; Dangoumau, Audrey; Gouel, Flore; Vourc'h, Patrick; Emond, Patrick; Laumonnier, Frédéric; Nadal-Desbarats, Lydie; Gordon, Paul H; Andres, Christian R; Blasco, Hélène

    2016-12-01

    This study aims to develop a cellular metabolomics model that reproduces the pathophysiological conditions found in amyotrophic lateral sclerosis in order to improve knowledge of disease physiology. We used a co-culture model combining the motor neuron-like cell line NSC-34 and the astrocyte clone C8-D1A, with each over-expressing wild-type or G93C mutant human SOD1, to examine amyotrophic lateral sclerosis (ALS) physiology. We focused on the effects of mutant human SOD1 as well as oxidative stress induced by menadione on intracellular metabolism using a metabolomics approach through gas chromatography coupled with mass spectrometry (GC-MS) analysis. Preliminary non-supervised analysis by Principal Component Analysis (PCA) revealed that cell type, genetic environment, and time of culture influenced the metabolomics profiles. Supervised analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) on data from intracellular metabolomics profiles of SOD1 G93C co-cultures produced metabolites involved in glutamate metabolism and the tricarboxylic acid cycle (TCA) cycle. This study revealed the feasibility of using a metabolomics approach in a cellular model of ALS. We identified potential disruption of the TCA cycle and glutamate metabolism under oxidative stress, which is consistent with prior research in the disease. Analysis of metabolic alterations in an in vitro model is a novel approach to investigation of disease physiology.

  17. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

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    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  18. Utilization of Metabolomics to Identify Serum Biomarkers for Hepatocellular Carcinoma in Patients with Liver Cirrhosis

    Science.gov (United States)

    Ressom, Habtom W.; Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou, Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao, Yi; Wang, Jinlian; Di Poto, Cristina; Cheema, Amrita K.; Tadesse, Mahlet G.; Goldman, Radoslav; Shetty, Kirti

    2012-01-01

    Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in

  19. Metabolomic approach for identifying and visualizing molecular tissue markers in tadpoles of Xenopus tropicalis by mass spectrometry imaging

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    Naoko Goto-Inoue

    2016-09-01

    Full Text Available In developmental and cell biology it is crucial to evaluate the dynamic profiles of metabolites. An emerging frog model system using Xenopus tropicalis, whose genome sequence and inbred strains are available, is now ready for metabolomics investigation in amphibians. In this study we applied matrix-assisted laser desorption/ionization (MALDI-mass spectrometry imaging (MSI analysis to identify and visualize metabolomic molecular markers in tadpoles of Xenopus tropicalis. We detected tissue-specific peaks and visualized their distribution in tissues, and distinguished 19 tissues and their specific peaks. We identified, for the first time, some of their molecular localizations via tandem mass spectrometric analysis: hydrocortisone in artery, L-DOPA in rhombencephalon, taurine in eye, corticosterone in gill, heme in heart, inosine monophosphate and carnosine in muscle, dopamine in nerves, and phosphatidylethanolamine (16:0/20:4 in pharynx. This is the first MALDI-MSI study of X. tropicalis tadpoles, as in small tadpoles it is hard to distinguish and dissect the various organs. Furthermore, until now there has been no data about the metabolomic profile of each organ. Our results suggest that MALDI-MSI is potentially a powerful tool for examining the dynamics of metabolomics in metamorphosis as well as conformational changes due to metabolic changes.

  20. A metabolomics approach to identify factors influencing glucosinolate thermal degradation rates in Brassica vegetables.

    Science.gov (United States)

    Hennig, K; de Vos, R C H; Maliepaard, C; Dekker, M; Verkerk, R; Bonnema, G

    2014-07-15

    Thermal processing of Brassica vegetables can lead to substantial loss of potential health-promoting glucosinolates (GLs). The extent of thermal degradation of a specific GL varies in different vegetables, possibly due to differences in the composition of other metabolites within the plant matrices. An untargeted metabolomics approach followed by random forest regression was applied to identify metabolites associated to thermal GL degradation in a segregating Brassica oleracea population. Out of 413 metabolites, 15 were associated with the degradation of glucobrassicin, six with that of glucoraphanin and two with both GLs. Among these 23 metabolites three were identified as flavonols (one kaempferol- and two quercetin-derivatives) and two as other GLs (4-methoxyglucobrassicin, gluconasturtiin). Twenty quantitative trait loci (QTLs) for these metabolites, which were associated with glucoraphanin and glucobrassicin degradation, were identified on linkage groups C01, C07 and C09. Two flavonols mapped on linkage groups C07 and C09 and co-localise with the QTL for GL degradation determined previously. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Metabolomic biomarkers identify differences in milk produced by Holstein cows and other minor dairy animals.

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    Yang, Yongxin; Zheng, Nan; Zhao, Xiaowei; Zhang, Yangdong; Han, Rongwei; Yang, Jinhui; Zhao, Shengguo; Li, Songli; Guo, Tongjun; Zang, Changjiang; Wang, Jiaqi

    2016-03-16

    Several milk metabolites are associated with breeds or species of dairy animals. A better understanding of milk metabolites from different dairy animals would advance their use in evaluating milk traits and detecting milk adulteration. The objective of this study was to characterize the milk metabolite profiles of Chinese Holstein, Jersey, yak, buffalo, goat, camel, and horse and identify any differences using non-targeted metabolomic approaches. Milk samples were tested using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS). Data were analyzed using a multivariate analysis of variance and differences in milk metabolites between Holstein and the other dairy animals were assessed using orthogonal partial least-squares discriminant analysis. Differential metabolites were identified and some metabolites, such as choline and succinic acid, were used to distinguish Holstein milk from that of the other studied animals. Metabolic pathway analysis of different metabolites revealed that glycerophospholipid metabolism as well as valine, leucine, and isoleucine biosynthesis were shared in the other ruminant animals (Jersey, buffalo, yak, and goat), and biosynthesis of unsaturated fatty acids was shared in the non-ruminant animals (camel and horse). These results can be useful for gaining a better understanding of the differences in milk synthesis between Holstein and the other dairy animals. Copyright © 2016. Published by Elsevier B.V.

  2. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

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    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O' Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  3. Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes

    OpenAIRE

    O?Kell, Allison L.; Garrett, Timothy J.; Wasserfall, Clive; Atkinson, Mark A.

    2017-01-01

    While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n?=?6) and healthy (n?=?6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of k...

  4. Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Ressom, Habtom W., E-mail: hwr@georgetown.edu [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao Yi; Wang Jinlian; Di Poto, Cristina; Cheema, Amrita K. [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Tadesse, Mahlet G. [Department of Mathematics and Statistics, Georgetown University, Washington, DC 20057 (United States); Goldman, Radoslav [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Shetty, Kirti [Department of Surgery, Georgetown University Medical Center, Washington, DC 20057 (United States); Georgetown University Hospital, Washington, DC 20057 (United States)

    2012-09-19

    cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in high risk population of cirrhotic patients.

  5. Use of NMR metabolomic plasma profiling methodologies to identify illicit growth-promoting administrations

    NARCIS (Netherlands)

    Graham, S.F.; Ruiz Aracama, A.; Lommen, A.; Cannizzo, F.T.; Biolatti, B.; Elliott, C.T.; Mooney, M.H.

    2012-01-01

    Detection of growth-promoter use in animal production systems still proves to be an analytical challenge despite years of activity in the field. This study reports on the capability of NMR metabolomic profiling techniques to discriminate between plasma samples obtained from cattle treated with

  6. Identifying Potential Child Abuse through Oral Examination

    Directory of Open Access Journals (Sweden)

    Jillian N. Printz

    2017-01-01

    Full Text Available Limited reports of oropharyngeal trauma exist in the literature even though this type of injury is extremely common in pediatric populations. There are no widely agreed upon diagnostic and management tools for such injuries in abuse cases, emphasizing the importance of reporting rare cases of orofacial trauma. This case report of a soft palate laceration demonstrates an instance of initially unrecognized potential child abuse. We aim to clarify understanding of such injuries. Furthermore, the report highlights the need for recognition of oral signs of child abuse in order to promote early detection, reporting, and appropriate management.

  7. Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome.

    Science.gov (United States)

    Chang, Alice Y; Lalia, Antigoni Z; Jenkins, Gregory D; Dutta, Tumpa; Carter, Rickey E; Singh, Ravinder J; Nair, K Sreekumaran

    2017-06-01

    Polycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS). Twenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses. This multiethnic, obese sample was matched by age (PCOS, 37±6; MetS, 40±6years) and body mass index (BMI) (PCOS, 34.6±5.1; MetS, 33.7±5.2kg/m 2 ). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P=.02), essential amino acids (P=.03), the essential amino acid lysine (P=.02), and the lysine metabolite α-aminoadipic acid (P=.02) in models adjusted for surrogate variables representing technical variation in metabolites. No significant differences between

  8. HPLC-based metabolomics to identify cytotoxic compounds from Plectranthus amboinicus (Lour.) Spreng against human breast cancer MCF-7Cells.

    Science.gov (United States)

    Yulianto, Wahid; Andarwulan, Nuri; Giriwono, Puspo Edi; Pamungkas, Joko

    2016-12-15

    The objective of this study was to identify the active compounds in Plectranthus amboinicus (Lour.) Spreng which play a role to inhibit viability of breast cancer MCF-7 cells using HPLC-based metabolomics approach. Five fractions of the plant extract were observed including ethanol, hexane, chloroform, ethyl acetate and water fraction. There were 45 HPLC chromatograms resulted from 5 fractions with 3 replications and 3 wavelengths detection. The chromatograms were compared to the data of IC 50 from MTT assay of each fraction against human breast cancer MCF-7 cells using metabolomics. The OPLS analysis result promptly pointed towards a chloroform fraction at retention time of 40.16-41.28min that has the greatest contribution to the cytotoxic activity. The data of mass spectra indicated that an abietane diterpene namely 7-acetoxy-6-hydroxyroyleanone was the main compound that contributed to the cytotoxic activity. This metabolomics application method can be used as a quick preliminary guideline to uncover the most dominant compound related to the bioactivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Andrea Ganna

    2014-12-01

    Full Text Available Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD. We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up with validation in 1,670 individuals (282 events; 3.9 y. median follow-up. Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001, lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001, monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011 and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%. MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002 of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05 on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.

  10. Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Bertini, Ivano; Cacciatore, Stefano; Jensen, Benny V

    2012-01-01

    survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of m...

  11. Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.

    Science.gov (United States)

    Laíns, Inês; Kelly, Rachel S; Miller, John B; Silva, Rufino; Vavvas, Demetrios G; Kim, Ivana K; Murta, Joaquim N; Lasky-Su, Jessica; Miller, Joan W; Husain, Deeba

    2018-02-01

    To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). Cross-sectional observational study. We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10 -9 ) among these metabolites. Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest

  12. Knowns and unknowns in metabolomics identified by multidimensional NMR and hybrid MS/NMR methods

    Energy Technology Data Exchange (ETDEWEB)

    Bingol, Kerem; Brüschweiler, Rafael

    2017-02-01

    Metabolomics continues to make rapid progress through the development of new and better methods and their applications to gain insight into the metabolism of a wide range of different biological systems from a systems biology perspective. Customization of NMR databases and search tools allows the faster and more accurate identification of known metabolites, whereas the identification of unknowns, without a need for extensive purification, requires new strategies to integrate NMR with mass spectrometry, cheminformatics, and computational methods. For some applications, the use of covalent and non-covalent attachments in the form of labeled tags or nanoparticles can significantly reduce the complexity of these tasks.

  13. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    Directory of Open Access Journals (Sweden)

    Vijay C Antharam

    Full Text Available Clostridium difficile infection (CDI is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7 and healthy controls (n = 6. From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA, 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  14. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    Science.gov (United States)

    Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  15. Metabolomics analysis identifies intestinal microbiota-derived biomarkers of colonization resistance in clindamycin-treated mice.

    Directory of Open Access Journals (Sweden)

    Robin L P Jump

    Full Text Available The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment.To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of antibiotic-treated mice, stool samples were analyzed using quantitative real-time polymerase chain reaction to assess changes in the microbiota and using non-targeted metabolic profiling. To assess whether the findings were applicable to another antibiotic class that suppresses intestinal anaerobes, similar experiments were conducted with piperacillin/tazobactam.Colonization resistance began to recover within 5 days and was intact by 12 days after clindamycin treatment, coinciding with the recovery bacteria from the families Lachnospiraceae and Ruminococcaceae, both part of the phylum Firmicutes. Clindamycin treatment caused marked changes in metabolites present in fecal specimens. Of 484 compounds analyzed, 146 (30% exhibited a significant increase or decrease in concentration during clindamycin treatment followed by recovery to baseline that coincided with restoration of in vivo colonization resistance. Identified as potential biomarkers of colonization resistance, these compounds included intermediates in carbohydrate or protein metabolism that increased (pentitols, gamma-glutamyl amino acids and inositol metabolites or decreased (pentoses, dipeptides with clindamycin treatment. Piperacillin

  16. Comprehensive Metabolomic, Lipidomic and Microscopic Profiling of Yarrowia lipolytica during Lipid Accumulation Identifies Targets for Increased Lipogenesis.

    Directory of Open Access Journals (Sweden)

    Kyle R Pomraning

    Full Text Available Yarrowia lipolytica is an oleaginous ascomycete yeast that accumulates large amounts of lipids and has potential as a biofuel producing organism. Despite a growing scientific literature focused on lipid production by Y. lipolytica, there remain significant knowledge gaps regarding the key biological processes involved. We applied a combination of metabolomic and lipidomic profiling approaches as well as microscopic techniques to identify and characterize the key pathways involved in de novo lipid accumulation from glucose in batch cultured, wild-type Y. lipolytica. We found that lipids accumulated rapidly and peaked at 48 hours during the five day experiment, concurrent with a shift in amino acid metabolism. We also report that exhaustion of extracellular sugars coincided with thickening of the cell wall, suggesting that genes involved in cell wall biogenesis may be a useful target for improving the efficiency of lipid producing yeast strains.

  17. Comprehensive Metabolomic, Lipidomic and Microscopic Profiling of Yarrowia lipolytica during Lipid Accumulation Identifies Targets for Increased Lipogenesis

    Science.gov (United States)

    Pomraning, Kyle R.; Wei, Siwei; Karagiosis, Sue A.; Kim, Young-Mo; Dohnalkova, Alice C.; Arey, Bruce W.; Bredeweg, Erin L.; Orr, Galya; Metz, Thomas O.; Baker, Scott E.

    2015-01-01

    Yarrowia lipolytica is an oleaginous ascomycete yeast that accumulates large amounts of lipids and has potential as a biofuel producing organism. Despite a growing scientific literature focused on lipid production by Y. lipolytica, there remain significant knowledge gaps regarding the key biological processes involved. We applied a combination of metabolomic and lipidomic profiling approaches as well as microscopic techniques to identify and characterize the key pathways involved in de novo lipid accumulation from glucose in batch cultured, wild-type Y. lipolytica. We found that lipids accumulated rapidly and peaked at 48 hours during the five day experiment, concurrent with a shift in amino acid metabolism. We also report that exhaustion of extracellular sugars coincided with thickening of the cell wall, suggesting that genes involved in cell wall biogenesis may be a useful target for improving the efficiency of lipid producing yeast strains. PMID:25905710

  18. Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity.

    Science.gov (United States)

    Videhult Pierre, Pernilla; Haglöf, Jakob; Linder, Birgitta; Engskog, Mikael K R; Arvidsson, Torbjörn; Pettersson, Curt; Fransson, Anette; Laurell, Göran

    2017-10-01

    Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo. To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity. Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS. Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.

  19. Metabolome analysis of Arabidopsis thaliana roots identifies a key metabolic pathway for iron acquisition.

    Directory of Open Access Journals (Sweden)

    Holger Schmidt

    Full Text Available Fe deficiency compromises both human health and plant productivity. Thus, it is important to understand plant Fe acquisition strategies for the development of crop plants which are more Fe-efficient under Fe-limited conditions, such as alkaline soils, and have higher Fe density in their edible tissues. Root secretion of phenolic compounds has long been hypothesized to be a component of the reduction strategy of Fe acquisition in non-graminaceous plants. We therefore subjected roots of Arabidopsis thaliana plants grown under Fe-replete and Fe-deplete conditions to comprehensive metabolome analysis by gas chromatography-mass spectrometry and ultra-pressure liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry. Scopoletin and other coumarins were found among the metabolites showing the strongest response to two different Fe-limited conditions, the cultivation in Fe-free medium and in medium with an alkaline pH. A coumarin biosynthesis mutant defective in ortho-hydroxylation of cinnamic acids was unable to grow on alkaline soil in the absence of Fe fertilization. Co-cultivation with wild-type plants partially rescued the Fe deficiency phenotype indicating a contribution of extracellular coumarins to Fe solubilization. Indeed, coumarins were detected in root exudates of wild-type plants. Direct infusion mass spectrometry as well as UV/vis spectroscopy indicated that coumarins are acting both as reductants of Fe(III and as ligands of Fe(II.

  20. New biomarkers of coffee consumption identified by the non-targeted metabolomic profiling of cohort study subjects.

    Directory of Open Access Journals (Sweden)

    Joseph A Rothwell

    Full Text Available Coffee contains various bioactives implicated with human health and disease risk. To accurately assess the effects of overall consumption upon health and disease, individual intake must be measured in large epidemiological studies. Metabolomics has emerged as a powerful approach to discover biomarkers of intake for a large range of foods. Here we report the profiling of the urinary metabolome of cohort study subjects to search for new biomarkers of coffee intake. Using repeated 24-hour dietary records and a food frequency questionnaire, 20 high coffee consumers (183-540 mL/d and 19 low consumers were selected from the French SU.VI.MAX2 cohort. Morning spot urine samples from each subject were profiled by high-resolution mass spectrometry. Partial least-square discriminant analysis of multidimensional liquid chromatography-mass spectrometry data clearly distinguished high consumers from low via 132 significant (p-value<0.05 discriminating features. Ion clusters whose intensities were most elevated in the high consumers were annotated using online and in-house databases and their identities checked using commercial standards and MS-MS fragmentation. The best discriminants, and thus potential markers of coffee consumption, were the glucuronide of the diterpenoid atractyligenin, the diketopiperazine cyclo(isoleucyl-prolyl, and the alkaloid trigonelline. Some caffeine metabolites, such as 1-methylxanthine, were also among the discriminants, however caffeine may be consumed from other sources and its metabolism is subject to inter-individual variation. Receiver operating characteristics curve analysis showed that the biomarkers identified could be used effectively in combination for increased sensitivity and specificity. Once validated in other cohorts or intervention studies, these specific single or combined biomarkers will become a valuable alternative to assessment of coffee intake by dietary survey and finally lead to a better understanding of

  1. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

    Science.gov (United States)

    Vincent, Isabel M; Daly, Rónán; Courtioux, Bertrand; Cattanach, Amy M; Biéler, Sylvain; Ndung'u, Joseph M; Bisser, Sylvie; Barrett, Michael P

    2016-12-01

    Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control.

  2. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Isabel M Vincent

    2016-12-01

    Full Text Available Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF. Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity and stage of disease (92% sensitivity and 81% specificity. A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages versus control.

  3. Nutritional Metabolomics

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde

    Metabolomics provides a holistic approach to investigate the perturbations in human metabolism with respect to a specific exposure. In nutritional metabolomics, the research question is generally related to the effect of a specific food intake on metabolic profiles commonly of plasma or urine...... strategy influences the patterns identified as important for the nutritional question under study. Therefore, in depth understanding of the study design and the specific effects of the analytical technology on the produced data is extremely important to achieve high quality data handling. Besides data...... handling, this thesis also deals with biological interpretation of postprandial metabolism and trans fatty acid (TFA) intake. Two nutritional issues were objects of investigation: 1) metabolic states as a function of time since the last meal and 2) markers related to intakes of cis- and trans-fat. Plasma...

  4. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    Directory of Open Access Journals (Sweden)

    Tomohiro Osaki

    2015-08-01

    Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

  5. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

    Science.gov (United States)

    Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

    2015-12-01

    Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

  6. Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

    Science.gov (United States)

    Steelman, Samantha M; Johnson, Philip; Jackson, Amy; Schulze, James; Chowdhary, Bhanu P

    2014-05-15

    Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis. Copyright © 2014 the American Physiological Society.

  7. Transcriptomic and metabolomic analyses identify a role for chlorophyll catabolism and phytoalexin during Medicago nonhost resistance against Asian soybean rust.

    Science.gov (United States)

    Ishiga, Yasuhiro; Uppalapati, Srinivasa Rao; Gill, Upinder S; Huhman, David; Tang, Yuhong; Mysore, Kirankumar S

    2015-08-12

    Asian soybean rust (ASR) caused by Phakopsora pachyrhizi is a devastating foliar disease affecting soybean production worldwide. Understanding nonhost resistance against ASR may provide an avenue to engineer soybean to confer durable resistance against ASR. We characterized a Medicago truncatula-ASR pathosystem to study molecular mechanisms of nonhost resistance. Although urediniospores formed appressoria and penetrated into epidermal cells of M. truncatula, P. pachyrhizi failed to sporulate. Transcriptomic analysis revealed the induction of phenylpropanoid, flavonoid and isoflavonoid metabolic pathway genes involved in the production of phytoalexin medicarpin in M. truncatula upon infection with P. pachyrhizi. Furthermore, genes involved in chlorophyll catabolism were induced during nonhost resistance. We further characterized one of the chlorophyll catabolism genes, Stay-green (SGR), and demonstrated that the M. truncatula sgr mutant and alfalfa SGR-RNAi lines showed hypersensitive-response-like enhanced cell death upon inoculation with P. pachyrhizi. Consistent with transcriptomic analysis, metabolomic analysis also revealed the accumulation of medicarpin and its intermediate metabolites. In vitro assay showed that medicarpin inhibited urediniospore germination and differentiation. In addition, several triterpenoid saponin glycosides accumulated in M. truncatula upon inoculation with P. pachyrhizi. In summary, using multi-omic approaches, we identified a correlation between phytoalexin production and M. truncatula defense responses against ASR.

  8. Metabolomic analysis of anti-hypoxia and anti-anxiety effects of Fu Fang Jin Jing Oral Liquid.

    Directory of Open Access Journals (Sweden)

    Xia Liu

    Full Text Available BACKGROUND: Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics. METHODS: In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin and oxygen consumption increasing (exhaustive swimming were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified. RESULTS: Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect. CONCLUSIONS: FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug

  9. A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women.

    Science.gov (United States)

    McMillan, Amy; Rulisa, Stephen; Sumarah, Mark; Macklaim, Jean M; Renaud, Justin; Bisanz, Jordan E; Gloor, Gregory B; Reid, Gregor

    2015-09-21

    Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV include 2-hydroxyisovalerate and γ-hydroxybutyrate (GHB), but not succinate, which is produced by both Lactobacillus crispatus and BV-associated anaerobes in vitro. Biomarkers associated with high diversity and clinical BV are independent of pregnancy status, and were validated in a blinded replication cohort from Tanzania (n = 45), where we predicted clinical BV with 91% accuracy. Correlations between the metabolome and microbiota identified Gardnerella vaginalis as a putative producer of GHB, and we demonstrate production by this species in vitro. This work illustrates how changes in community structure alter the chemical composition of the vagina, and identifies highly specific biomarkers for a common condition.

  10. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Science.gov (United States)

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

  11. The food metabolome

    DEFF Research Database (Denmark)

    Scalbert, Augustin; Brennan, Lorraine; Manach, Claudine

    2014-01-01

    The food metabolome is defined as the part of the human metabolome directly derived from the digestion and biotransformation of foods and their constituents. With >25,000 compounds known in various foods, the food metabolome is extremely complex, with a composition varying widely according...... to the diet. By its very nature it represents a considerable and still largely unexploited source of novel dietary biomarkers that could be used to measure dietary exposures with a high level of detail and precision. Most dietary biomarkers currently have been identified on the basis of our knowledge of food...... by the recent identification of novel biomarkers of intakes for fruit, vegetables, beverages, meats, or complex diets. Moreover, examples also show how the scrutiny of the food metabolome can lead to the discovery of bioactive molecules and dietary factors associated with diseases. However, researchers still...

  12. Linking gene regulation and the exo-metabolome: A comparative transcriptomics approach to identify genes that impact on the production of volatile aroma compounds in yeast

    Directory of Open Access Journals (Sweden)

    Bauer Florian F

    2008-11-01

    Full Text Available Abstract Background 'Omics' tools provide novel opportunities for system-wide analysis of complex cellular functions. Secondary metabolism is an example of a complex network of biochemical pathways, which, although well mapped from a biochemical point of view, is not well understood with regards to its physiological roles and genetic and biochemical regulation. Many of the metabolites produced by this network such as higher alcohols and esters are significant aroma impact compounds in fermentation products, and different yeast strains are known to produce highly divergent aroma profiles. Here, we investigated whether we can predict the impact of specific genes of known or unknown function on this metabolic network by combining whole transcriptome and partial exo-metabolome analysis. Results For this purpose, the gene expression levels of five different industrial wine yeast strains that produce divergent aroma profiles were established at three different time points of alcoholic fermentation in synthetic wine must. A matrix of gene expression data was generated and integrated with the concentrations of volatile aroma compounds measured at the same time points. This relatively unbiased approach to the study of volatile aroma compounds enabled us to identify candidate genes for aroma profile modification. Five of these genes, namely YMR210W, BAT1, AAD10, AAD14 and ACS1 were selected for overexpression in commercial wine yeast, VIN13. Analysis of the data show a statistically significant correlation between the changes in the exo-metabome of the overexpressing strains and the changes that were predicted based on the unbiased alignment of transcriptomic and exo-metabolomic data. Conclusion The data suggest that a comparative transcriptomics and metabolomics approach can be used to identify the metabolic impacts of the expression of individual genes in complex systems, and the amenability of transcriptomic data to direct applications of

  13. Discriminant biomarkers of acute respiratory distress syndrome associated to H1N1 influenza identified by metabolomics HPLC-QTOF-MS/MS platform.

    Science.gov (United States)

    Ferrarini, Alessia; Righetti, Laura; Martínez, Ma Paz; Fernández-López, Mariano; Mastrangelo, Annalaura; Horcajada, Juan P; Betbesé, Antoni; Esteban, Andrés; Ordóñez, Jordi; Gea, Joaquín; Cabello, Jesús Ruiz; Pellati, Federica; Lorente, José A; Nin, Nicolás; Rupérez, Francisco J

    2017-09-01

    Acute respiratory distress syndrome (ARDS) is a serious complication of influenza A (H1N1) virus infection. Its pathogenesis is unknown and biomarkers are lacking. Untargeted metabolomics allows the analysis of the whole metabolome in a biological compartment, identifying patterns associated with specific conditions. We hypothesized that LC-MS could help identify discriminant metabolites able to define the metabolic alterations occurring in patients with influenza A (H1N1) virus infection that developed ARDS. Serum samples from patients diagnosed with 2009 influenza A (H1N1) virus infection with (n = 25) or without (n = 32) ARDS were obtained on the day of hospital admission and analyzed by LC-MS/MS. Metabolite identification was determined by MS/MS analysis and analysis of standards. The specificity of the patterns identified was confirmed in patients without 2009 influenza A(H1N1) virus pneumonia (15 without and 17 with ARDS). Twenty-three candidate biomarkers were found to be significantly different between the two groups, including lysophospholipids and sphingolipids related to inflammation; bile acids, tryptophan metabolites, and thyroxine, related to the metabolism of the gut microflora. Confirmation results demonstrated the specificity of major alterations occurring in ARDS patients with influenza A (H1N1) virus infection. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    International Nuclear Information System (INIS)

    Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

    2011-01-01

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

  15. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

  16. Quality assurance of metabolomics.

    Science.gov (United States)

    Bouhifd, Mounir; Beger, Richard; Flynn, Thomas; Guo, Lining; Harris, Georgina; Hogberg, Helena; Kaddurah-Daouk, Rima; Kamp, Hennicke; Kleensang, Andre; Maertens, Alexandra; Odwin-DaCosta, Shelly; Pamies, David; Robertson, Donald; Smirnova, Lena; Sun, Jinchun; Zhao, Liang; Hartung, Thomas

    2015-01-01

    Metabolomics promises a holistic phenotypic characterization of biological responses to toxicants. This technology is based on advanced chemical analytical tools with reasonable throughput, including mass-spectroscopy and NMR. Quality assurance, however - from experimental design, sample preparation, metabolite identification, to bioinformatics data-mining - is urgently needed to assure both quality of metabolomics data and reproducibility of biological models. In contrast to microarray-based transcriptomics, where consensus on quality assurance and reporting standards has been fostered over the last two decades, quality assurance of metabolomics is only now emerging. Regulatory use in safety sciences, and even proper scientific use of these technologies, demand quality assurance. In an effort to promote this discussion, an expert workshop discussed the quality assurance needs of metabolomics. The goals for this workshop were 1) to consider the challenges associated with metabolomics as an emerging science, with an emphasis on its application in toxicology and 2) to identify the key issues to be addressed in order to establish and implement quality assurance procedures in metabolomics-based toxicology. Consensus has still to be achieved regarding best practices to make sure sound, useful, and relevant information is derived from these new tools.

  17. Altered post-mortem metabolism identified in very fast chilled lamb M. longissimus thoracis et lumborum using metabolomic analysis.

    Science.gov (United States)

    Warner, Robyn D; Jacob, Robin H; Rosenvold, Katja; Rochfort, Simone; Trenerry, Craige; Plozza, Tim; McDonagh, Matthew B

    2015-10-01

    The aim of this experiment was to use metabolomic techniques to investigate the energy metabolism in lamb M. longissimus thoracis et lumborum subjected to very fast chilling (VFC) post-mortem. The tissue was prepared by 2 different operators and subjected to very fast chilling (less than 0°C within 1.5h of slaughter) or typical chilling regimes (Control; 0°C within 22h of slaughter). Non-targeted metabolomic analysis ((1)H NMR) and targeted analysis ((31)P NMR, HPLC-PDA and HPLC-MS/MS) were used to examine the change in muscle metabolites post-mortem. One VFC treatment, which resulted in a colder core temperature and more tender meat, had higher levels of glycolytic intermediate metabolites pre-rigor as well as more of the end-products of adenosine and nicotine nucleotide metabolism pre-rigor, relative to conventionally chilled treatments. In conclusion, VFC to less than 0°C within 1.5h of slaughter causes considerable changes in metabolism and rigor onset, which are associated with tender meat. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  18. A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases.

    Science.gov (United States)

    Chassagne, François; Haddad, Mohamed; Amiel, Aurélien; Phakeovilay, Chiobouaphong; Manithip, Chanthanom; Bourdy, Geneviève; Deharo, Eric; Marti, Guillaume

    2018-02-23

    Liver cancer is a major health burden in Southeast Asia, and most patients turn towards the use of medicinal plants to alleviate their symptoms. The aim of this work was to apply to Southeast Asian plants traditionally used to treat liver disorders, a successive ranking strategy based on a comprehensive review of the literature and metabolomic data in order to relate ethnopharmacological relevance to chemical entities of interest. We analyzed 45 publications resulting in a list of 378 plant species, and our point system based on the frequency of citation in the literature allowed the selection of 10 top ranked species for further collection and extraction. Extracts of these plants were tested for their in vitro anti-proliferative activities on HepG2 cells. Ethanolic extracts of Andrographis paniculata, Oroxylum indicum, Orthosiphon aristatus and Willughbeia edulis showed the highest anti-proliferative effects (IC 50  = 195.9, 64.1, 71.3 and 66.7 μg/ml, respectively). A metabolomic ranking model was performed to annotate compounds responsible for the anti-proliferative properties of A. paniculata (andrographolactone and dehydroandrographolide), O. indicum (baicalein, chrysin, oroxylin A and scutellarein), O. aristatus (5-desmethylsinensetin) and W. edulis (parabaroside C and procyanidin). Overall, our dereplicative approach combined with a bibliographic scoring system allowed us to rapidly decipher the molecular basis of traditionally used medicinal plants. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

    Science.gov (United States)

    Zeleznik, O A; Poole, E M; Lindstrom, S; Kraft, P; Van Hylckama Vlieg, A; Lasky-Su, J A; Harrington, L B; Hagan, K; Kim, J; Parry, B A; Giordano, N; Kabrhel, C

    2018-03-01

    Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the

  20. A non-targeted metabolomic approach to identify food markers to support discrimination between organic and conventional tomato crops.

    Science.gov (United States)

    Martínez Bueno, María Jesús; Díaz-Galiano, Francisco José; Rajski, Łukasz; Cutillas, Víctor; Fernández-Alba, Amadeo R

    2018-04-20

    In the last decade, the consumption trend of organic food has increased dramatically worldwide. However, the lack of reliable chemical markers to discriminate between organic and conventional products makes this market susceptible to food fraud in products labeled as "organic". Metabolomic fingerprinting approach has been demonstrated as the best option for a full characterization of metabolome occurring in plants, since their pattern may reflect the impact of both endogenous and exogenous factors. In the present study, advanced technologies based on high performance liquid chromatography-high-resolution accurate mass spectrometry (HPLC-HRAMS) has been used for marker search in organic and conventional tomatoes grown in greenhouse under controlled agronomic conditions. The screening of unknown compounds comprised the retrospective analysis of all tomato samples throughout the studied period and data processing using databases (mzCloud, ChemSpider and PubChem). In addition, stable nitrogen isotope analysis (δ 15 N) was assessed as a possible indicator to support discrimination between both production systems using crop/fertilizer correlations. Pesticide residue analyses were also applied as a well-established way to evaluate the organic production. Finally, the evaluation by combined chemometric analysis of high-resolution accurate mass spectrometry (HRAMS) and δ 15 N data provided a robust classification model in accordance with the agricultural practices. Principal component analysis (PCA) showed a sample clustering according to farming systems and significant differences in the sample profile was observed for six bioactive components (L-tyrosyl-L-isoleucyl-L-threonyl-L-threonine, trilobatin, phloridzin, tomatine, phloretin and echinenone). Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Clinical Metabolomics and Glaucoma.

    Science.gov (United States)

    Barbosa-Breda, João; Himmelreich, Uwe; Ghesquière, Bart; Rocha-Sousa, Amândio; Stalmans, Ingeborg

    2018-01-01

    Glaucoma is one of the leading causes of irreversible blindness worldwide. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression. Metabolomics is the study of all metabolites in an organism, and it has the potential to provide a biomarker. This review summarizes the findings of metabolomics in glaucoma patients and explains why this field is promising for new research. We identified published studies that focused on metabolomics and ophthalmology. After providing an overview of metabolomics in ophthalmology, we focused on human glaucoma studies. Five studies have been conducted in glaucoma patients and all compared patients to healthy controls. Using mass spectrometry, significant differences were found in blood plasma in the metabolic pathways that involve palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors. For nuclear magnetic resonance spectroscopy, a high glutamine-glutamate/creatine ratio was found in the vitreous and lateral geniculate body; no differences were detected in the optic radiations, and a lower N-acetylaspartate/choline ratio was observed in the geniculocalcarine and striate areas. Metabolomics can move glaucoma care towards a personalized approach and provide new knowledge concerning the pathophysiology of glaucoma, which can lead to new therapeutic options. © 2017 S. Karger AG, Basel.

  2. Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Joong Kyong Ahn

    2017-11-01

    Full Text Available Diagnosing Behcet’s disease (BD is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS. Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974. OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%. We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.

  3. Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet's Disease by Gas Chromatography/Time-of-Flight-Mass Spectrometry.

    Science.gov (United States)

    Ahn, Joong Kyong; Kim, Jungyeon; Hwang, Jiwon; Song, Juhwan; Kim, Kyoung Heon; Cha, Hoon-Suk

    2017-11-02

    Diagnosing Behcet's disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF-MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF-MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R ² X of 0.231, R ² Y of 0.804, and Q ² of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF-MS.

  4. NMR-based metabolomics applications

    DEFF Research Database (Denmark)

    Iaccarino, Nunzia

    juice from ancient Danish apple cultivars. Both studies revealed variety-related peculiarities that would have been difficult to detect by means of traditional analysis. The second part of the project includes four metabolomics studies performed on samples of biological origin. In particular, the first......Metabolomics is the scientific discipline that identifies and quantifies endogenous and exogenous metabolites in different biological samples. Metabolites are crucial components of a biological system and they are highly informative about its functional state, due to their closeness to the organism...... focused on the analysis of various samples covering a wide range of fields, namely, food and nutraceutical sciences, cell metabolomics and medicine using a metabolomics approach. Indeed, the first part of the thesis describes two exploratory studies performed on Algerian extra virgin olive oil and apple...

  5. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics

    Directory of Open Access Journals (Sweden)

    Qi Li

    2016-06-01

    Full Text Available Hyperlipidemia (HLP is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05 during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05 in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP.

  6. Readily Identifiable Risk Factors of Nursing Home Residents' Oral Hygiene: Dementia, Hospice, and Length of Stay.

    Science.gov (United States)

    Zimmerman, Sheryl; Austin, Sophie; Cohen, Lauren; Reed, David; Poole, Patricia; Ward, Kimberly; Sloane, Philip D

    2017-11-01

    The poor oral hygiene of nursing home (NH) residents is a matter of increasing concern, especially because of its relationship with pneumonia and other health events. Because details and related risk factors in this area are scant and providers need to be able to easily identify those residents at most risk, this study comprehensively examined the plaque, gingival, and denture status of NH residents, as well as readily available correlates of those indicators of oral hygiene, including items from the Minimum Data Set (MDS). Oral hygiene assessment and chart abstract conducted on a cross-section of NH residents. NHs in North Carolina (N = 14). NH residents (N = 506). Descriptive data from the MDS and assessments using three standardized measures: the Plaque Index for Long-Term Care (PI-LTC), the Gingival Index for Long-Term Care (GI-LTC), and the Denture Plaque Index (DPI). Oral hygiene scores averaged 1.7 (of 3) for the PI-LTC, 1.5 (of 4) for the GI-LTC, and 2.2 (of 4) for the DPI. Factors most strongly associated with poor oral hygiene scores included having dementia, being on hospice care, and longer stay. MDS ratings of gingivitis differed significantly from oral hygiene assessments. The findings identify resident subgroups at especially high risk of poor oral health who can be targeted in quality improvement efforts related to oral hygiene; they also indicate need to improve the accuracy of how MDS items are completed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  7. Identifying factors to improve oral cancer screening uptake: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Fatemeh Vida Zohoori

    Full Text Available To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake.Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week, irregular dental attenders living in economically deprived areas of Teesside.There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is 'inaccessible' on a physical and psychological level, costly, a 'tooth specialist' not a 'mouth specialist', and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer.The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a "health" screening setting as opposed to a "dental" setting for such checks.

  8. Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    You Jin Kim

    2017-03-01

    Full Text Available Various statistical approaches can be applied to integrate traditional and omics biomarkers, allowing the discovery of prognostic markers to classify subjects into poor and good prognosis groups in terms of responses to nutritional interventions. Here, we performed a prototype study to identify metabolites that predict responses to an intervention against oxidative stress and inflammation, using a data set from a randomized controlled trial evaluating Korean black raspberry (KBR in sedentary overweight/obese subjects. First, a linear mixed-effects model analysis with multiple testing correction showed that four-week consumption of KBR significantly changed oxidized glutathione (GSSG, q = 0.027 level, the ratio of reduced glutathione (GSH to GSSG (q = 0.039 in erythrocytes, malondialdehyde (MDA, q = 0.006 and interleukin-6 (q = 0.006 levels in plasma, and seventeen NMR metabolites in urine compared with those in the placebo group. A subsequent generalized linear mixed model analysis showed linear correlations between baseline urinary glycine and N-phenylacetylglycine (PAG and changes in the GSH:GSSG ratio (p = 0.008 and 0.004 as well as between baseline urinary adenine and changes in MDA (p = 0.018. Then, receiver operating characteristic analysis revealed that a two-metabolite set (glycine and PAG had the strongest prognostic relevance for future interventions against oxidative stress (the area under the curve (AUC = 0.778. Leave-one-out cross-validation confirmed the accuracy of prediction (AUC = 0.683. The current findings suggest that a higher level of this two-metabolite set at baseline is useful for predicting responders to dietary interventions in subjects with oxidative stress and inflammation, contributing to the emergence of personalized nutrition.

  9. Oral and Tympanic Membrane Temperatures are Inaccurate to Identify Fever in Emergency Department Adults

    Directory of Open Access Journals (Sweden)

    Robert Silverman

    2011-05-01

    Full Text Available Introduction: Identifying fever can influence management of the emergency department (ED patient, including diagnostic testing, treatment, and disposition. We set out to determine how well oral and tympanic membrane (TM temperatures compared with rectal measurements. Methods: A convenience sample of consecutively adult ED patients had oral, TM, and rectal temperatures performed within several minutes of each other. Descriptive statistics, Bland–Altman agreement matrices with 95% confidence interval (CI, and measures of test performance, including sensitivity, specificity, predictive values, and interval likelihood ratios were performed. Results: A total of 457 patients were enrolled with an average age of 64 years (standard deviation: 19 years. Mean temperatures were: oral (98.38F, TM (99.68F, and rectal (99.48F. The mean difference in rectal and oral temperatures was 1.18F, although there was considerable lack of agreement between oral and rectal temperatures, with the oral temperature as much as 2.918F lower or 0.748F higher than the rectal measurement (95% CI. Although the difference in mean temperature between right TM and rectal temperature was only 0.228F, the right TM was lower than rectal by up to 1.618F or greater by up to 2.058F (95% CI. Test performance varied as the positive predictive value of the oral temperature was 97% and for tympanic temperature was 55% (relative to a rectal temperature of 100.48F or higher. Comparative findings differed even at temperatures considered in the normal range; among patients with an oral temperature of 98.0 to 98.9, 38% (25/65 were found to have a rectal temperature of 100.4 or higher, while among patients with a TM of 98.0 to 98.9, only 7% (10/134 were found to have a rectal temperature of 100.4 or higher. Conclusion: In conclusion, the oral and tympanic temperature readings are not equivalent to rectal thermometry readings. Oral thermometry frequently underestimates the temperature relative to

  10. Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

    Science.gov (United States)

    Polachini, Giovana M.; Sobral, Lays M.; Mercante, Ana M. C.; Paes-Leme, Adriana F.; Xavier, Flávia C. A.; Henrique, Tiago; Guimarães, Douglas M.; Vidotto, Alessandra; Fukuyama, Erica E.; Góis-Filho, José F.; Cury, Patricia M.; Curioni, Otávio A.; Michaluart Jr, Pedro; Silva, Adriana M. A.; Wünsch-Filho, Victor; Nunes, Fabio D.; Leopoldino, Andréia M.; Tajara, Eloiza H.

    2012-01-01

    The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the “more-aggressive” group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the “less-aggressive” group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas. PMID:23227181

  11. Metabolic network segmentation: A probabilistic graphical modeling approach to identify the sites and sequential order of metabolic regulation from non-targeted metabolomics data.

    Directory of Open Access Journals (Sweden)

    Andreas Kuehne

    2017-06-01

    Full Text Available In recent years, the number of large-scale metabolomics studies on various cellular processes in different organisms has increased drastically. However, it remains a major challenge to perform a systematic identification of mechanistic regulatory events that mediate the observed changes in metabolite levels, due to complex interdependencies within metabolic networks. We present the metabolic network segmentation (MNS algorithm, a probabilistic graphical modeling approach that enables genome-scale, automated prediction of regulated metabolic reactions from differential or serial metabolomics data. The algorithm sections the metabolic network into modules of metabolites with consistent changes. Metabolic reactions that connect different modules are the most likely sites of metabolic regulation. In contrast to most state-of-the-art methods, the MNS algorithm is independent of arbitrary pathway definitions, and its probabilistic nature facilitates assessments of noisy and incomplete measurements. With serial (i.e., time-resolved data, the MNS algorithm also indicates the sequential order of metabolic regulation. We demonstrated the power and flexibility of the MNS algorithm with three, realistic case studies with bacterial and human cells. Thus, this approach enables the identification of mechanistic regulatory events from large-scale metabolomics data, and contributes to the understanding of metabolic processes and their interplay with cellular signaling and regulation processes.

  12. Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.

    Science.gov (United States)

    Aterido, Adrià; Julià, Antonio; Carreira, Patricia; Blanco, Ricardo; López-Longo, José Javier; Venegas, José Javier Pérez; Olivé, Àlex; Andreu, José Luís; Aguirre-Zamorano, Maria Ángeles; Vela, Paloma; Nolla, Joan M; Marenco-de la Fuente, José Luís; Zea, Antonio; Pego, José María; Freire, Mercedes; Díez, Elvira; López-Lasanta, María; López-Corbeto, Mireia; Palau, Núria; Tortosa, Raül; Gelpí, Josep Lluís; Absher, Devin; Myers, Richard M; Fernández-Nebro, Antonio; Marsal, Sara

    2017-06-15

    Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR ) oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis

  13. Metabolomics and Epidemiology Working Group

    Science.gov (United States)

    The Metabolomics and Epidemiology (MetEpi) Working Group promotes metabolomics analyses in population-based studies, as well as advancement in the field of metabolomics for broader biomedical and public health research.

  14. A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it.

    Science.gov (United States)

    Spicer, Rachel A; Steinbeck, Christoph

    2018-01-01

    Data sharing is being increasingly required by journals and has been heralded as a solution to the 'replication crisis'. (i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals' policies to those that publish the most metabolomics papers. A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications. Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data. Further efforts are required to improve data sharing in metabolomics.

  15. The same microbiota and a potentially discriminant metabolome in the saliva of omnivore, ovo-lacto-vegetarian and Vegan individuals.

    Directory of Open Access Journals (Sweden)

    Francesca De Filippis

    Full Text Available The salivary microbiota has been linked to both oral and non-oral diseases. Scant knowledge is available on the effect of environmental factors such as long-term dietary choices on the salivary microbiota and metabolome. This study analyzed the microbial diversity and metabolomic profiles of the saliva of 161 healthy individuals who followed an omnivore or ovo-lacto-vegetarian or vegan diet. A large core microbiota was identified, including 12 bacterial genera, found in >98% of the individuals. The subjects could be stratified into three "salivary types" that differed on the basis of the relative abundance of the core genera Prevotella, Streptococcus/Gemella and Fusobacterium/Neisseria. Statistical analysis indicated no effect of dietary habit on the salivary microbiota. Phylogenetic beta-diversity analysis consistently showed no differences between omnivore, ovo-lacto-vegetarian and vegan individuals. Metabolomic profiling of saliva using (1H-NMR and GC-MS/SPME identified diet-related biomarkers that enabled a significant discrimination between the 3 groups of individuals on the basis of their diet. Formate, urea, uridine and 5-methyl-3-hexanone could discriminate samples from omnivores, whereas 1-propanol, hexanoic acid and proline were characteristic of non-omnivore diets. Although the salivary metabolome can be discriminating for diet, the microbiota has a remarkable inter-individual stability and did not vary with dietary habits. Microbial homeostasis might be perturbed with sub-standard oral hygiene or other environmental factors, but there is no current indication that a choice of an omnivore, ovo-lacto-vegetarian or vegan diet can lead to a specific composition of the oral microbiota with consequences on the oral homeostasis.

  16. The same microbiota and a potentially discriminant metabolome in the saliva of omnivore, ovo-lacto-vegetarian and Vegan individuals.

    Science.gov (United States)

    De Filippis, Francesca; Vannini, Lucia; La Storia, Antonietta; Laghi, Luca; Piombino, Paola; Stellato, Giuseppina; Serrazanetti, Diana I; Gozzi, Giorgia; Turroni, Silvia; Ferrocino, Ilario; Lazzi, Camilla; Di Cagno, Raffaella; Gobbetti, Marco; Ercolini, Danilo

    2014-01-01

    The salivary microbiota has been linked to both oral and non-oral diseases. Scant knowledge is available on the effect of environmental factors such as long-term dietary choices on the salivary microbiota and metabolome. This study analyzed the microbial diversity and metabolomic profiles of the saliva of 161 healthy individuals who followed an omnivore or ovo-lacto-vegetarian or vegan diet. A large core microbiota was identified, including 12 bacterial genera, found in >98% of the individuals. The subjects could be stratified into three "salivary types" that differed on the basis of the relative abundance of the core genera Prevotella, Streptococcus/Gemella and Fusobacterium/Neisseria. Statistical analysis indicated no effect of dietary habit on the salivary microbiota. Phylogenetic beta-diversity analysis consistently showed no differences between omnivore, ovo-lacto-vegetarian and vegan individuals. Metabolomic profiling of saliva using (1)H-NMR and GC-MS/SPME identified diet-related biomarkers that enabled a significant discrimination between the 3 groups of individuals on the basis of their diet. Formate, urea, uridine and 5-methyl-3-hexanone could discriminate samples from omnivores, whereas 1-propanol, hexanoic acid and proline were characteristic of non-omnivore diets. Although the salivary metabolome can be discriminating for diet, the microbiota has a remarkable inter-individual stability and did not vary with dietary habits. Microbial homeostasis might be perturbed with sub-standard oral hygiene or other environmental factors, but there is no current indication that a choice of an omnivore, ovo-lacto-vegetarian or vegan diet can lead to a specific composition of the oral microbiota with consequences on the oral homeostasis.

  17. Metabolome strategy against Edwardsiella tarda infection through glucose-enhanced metabolic modulation in tilapias.

    Science.gov (United States)

    Peng, Bo; Ma, Yan-Mei; Zhang, Jian-Ying; Li, Hui

    2015-08-01

    Edwardsiella tarda causes fish disease and great economic loss. However, metabolic strategy against the pathogen remains unexplored. In the present study, GC-MS based metabolomics was used to investigate the metabolic profile from tilapias infected by sublethal dose of E. tarda. The metabolic differences between the dying group and survival group allow the identification of key pathways and crucial metabolites during infections. More importantly, those metabolites may modulate the survival-related metabolome to enhance the anti-infective ability. Our data showed that tilapias generated two different strategies, survival-metabolome and death-metabolome, to encounter EIB202 infection, leading to differential outputs of the survival and dying. Glucose was the most crucial biomarker, which was upregulated and downregulated in the survival and dying groups, respectively. Exogenous glucose by injection or oral administration enhanced hosts' ability against EIB202 infection and increased the chances of survival. These findings highlight that host mounts the metabolic strategy to cope with bacterial infection, from which crucial biomarkers may be identified to enhance the metabolic strategy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Metabolomic Studies in Drosophila.

    Science.gov (United States)

    Cox, James E; Thummel, Carl S; Tennessen, Jason M

    2017-07-01

    Metabolomic analysis provides a powerful new tool for studies of Drosophila physiology. This approach allows investigators to detect thousands of chemical compounds in a single sample, representing the combined contributions of gene expression, enzyme activity, and environmental context. Metabolomics has been used for a wide range of studies in Drosophila , often providing new insights into gene function and metabolic state that could not be obtained using any other approach. In this review, we survey the uses of metabolomic analysis since its entry into the field. We also cover the major methods used for metabolomic studies in Drosophila and highlight new directions for future research. Copyright © 2017 by the Genetics Society of America.

  19. Nutritional Metabolomics

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde

    strategy influences the patterns identified as important for the nutritional question under study. Therefore, in depth understanding of the study design and the specific effects of the analytical technology on the produced data is extremely important to achieve high quality data handling. Besides data...

  20. Functional metabolomics reveals novel active products in the DHA metabolome

    Directory of Open Access Journals (Sweden)

    Masakazu eShinohara

    2012-04-01

    Full Text Available Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA. Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered (AT forms of protectins. The new oxygenated DHEA derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.

  1. Metabolomics in chemical ecology.

    Science.gov (United States)

    Kuhlisch, Constanze; Pohnert, Georg

    2015-07-01

    Chemical ecology elucidates the nature and role of natural products as mediators of organismal interactions. The emerging techniques that can be summarized under the concept of metabolomics provide new opportunities to study such environmentally relevant signaling molecules. Especially comparative tools in metabolomics enable the identification of compounds that are regulated during interaction situations and that might play a role as e.g. pheromones, allelochemicals or in induced and activated defenses. This approach helps overcoming limitations of traditional bioassay-guided structure elucidation approaches. But the power of metabolomics is not limited to the comparison of metabolic profiles of interacting partners. Especially the link to other -omics techniques helps to unravel not only the compounds in question but the entire biosynthetic and genetic re-wiring, required for an ecological response. This review comprehensively highlights successful applications of metabolomics in chemical ecology and discusses existing limitations of these novel techniques. It focuses on recent developments in comparative metabolomics and discusses the use of metabolomics in the systems biology of organismal interactions. It also outlines the potential of large metabolomics initiatives for model organisms in the field of chemical ecology.

  2. Metabolomic studies in pulmonology

    Directory of Open Access Journals (Sweden)

    R. R. Furina

    2015-01-01

    Full Text Available The review shows the results of metabolomic studies in pulmonology. The key idea of metabolomics is to detect specific biomarkers in a biological sample for the diagnosis of diseases of the bronchi and lung. Main methods for the separation and identification of volatile organic substances as biomarkers (gas chromatography, mass spectrometry, and nuclear magnetic resonance spectrometry used in metabolomics are given. A solid-phase microextraction method used to pre-prepare a sample is also covered. The results of laboratory tests for biomarkers for lung cancer, acute respiratory distress syndrome, chronic obstructive pulmonary disease, cystic fibrosis, chronic infections, and pulmonary tuberculosis are presented. In addition, emphasis is placed on the possibilities of metabolomics used in experimental medicine, including to the study of asthma. The information is of interest to both theorists and practitioners.

  3. Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats).

    Science.gov (United States)

    Miller, Marion G

    2007-02-01

    Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively explored. This review will use a SWOT analysis model to discuss some of the strengths, weaknesses, opportunities, and threats that are apparent to an investigator venturing into this relatively new field. SWOT has been used extensively in business settings to uncover new outlooks and identify problems that would impede progress. The field of environmental metabolomics provides great opportunities for discovery, and this is recognized by a high level of interest in potential applications. However, understanding the biological consequence of environmental exposures can be confounded by inter- and intra-individual differences. Metabolomic profiles can yield a plethora of data, the interpretation of which is complex and still being evaluated and researched. The development of the field will depend on the availability of technologies for data handling and that permit ready access metabolomic databases. Understanding the relevance of metabolomic endpoints to organism health vs adaptation vs variation is an important step in understanding what constitutes a substantive environmental threat. Metabolomic applications in reproductive research are discussed. Overall, the development of a comprehensive mechanistic-based interpretation of metabolomic changes offers the possibility of providing information that will significantly contribute to the protection of human health and the environment.

  4. oral

    African Journals Online (AJOL)

    Chlorhexidine 0,2% gluconate is used as a mouth rinse and is an effective antibacterial agent. Its primary side- effects are staining of the teeth and the oral mucosa, particularly the dorsal surface of the tongue. However, this is transient. It has been shown to be effective as a prophylactic agent in preventing oral candidosis in ...

  5. Possibility of the Use of Public Microarray Database for Identifying Significant Genes Associated with Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ki-Yeol Kim

    2012-03-01

    Full Text Available There are lots of studies attempting to identify the expression changes in oral squamous cell carcinoma. Most studies include insufficient samples to apply statistical methods for detecting significant gene sets. This study combined two small microarray datasets from a public database and identified significant genes associated with the progress of oral squamous cell carcinoma. There were different expression scales between the two datasets, even though these datasets were generated under the same platforms - Affymetrix U133A gene chips. We discretized gene expressions of the two datasets by adjusting the differences between the datasets for detecting the more reliable information. From the combination of the two datasets, we detected 51 significant genes that were upregulated in oral squamous cell carcinoma. Most of them were published in previous studies as cancer-related genes. From these selected genes, significant genetic pathways associated with expression changes were identified. By combining several datasets from the public database, sufficient samples can be obtained for detecting reliable information. Most of the selected genes were known as cancer-related genes, including oral squamous cell carcinoma. Several unknown genes can be biologically evaluated in further studies.

  6. Metabolomics to Explore Impact of Dairy Intake

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2015-06-01

    Full Text Available Dairy products are an important component in the Western diet and represent a valuable source of nutrients for humans. However, a reliable dairy intake assessment in nutrition research is crucial to correctly elucidate the link between dairy intake and human health. Metabolomics is considered a potential tool for assessment of dietary intake instead of traditional methods, such as food frequency questionnaires, food records, and 24-h recalls. Metabolomics has been successfully applied to discriminate between consumption of different dairy products under different experimental conditions. Moreover, potential metabolites related to dairy intake were identified, although these metabolites need to be further validated in other intervention studies before they can be used as valid biomarkers of dairy consumption. Therefore, this review provides an overview of metabolomics for assessment of dairy intake in order to better clarify the role of dairy products in human nutrition and health.

  7. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

    Full Text Available Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH, the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

  8. COnsortium of METabolomics Studies (COMETS)

    Science.gov (United States)

    The COnsortium of METabolomics Studies (COMETS) is an extramural-intramural partnership that promotes collaboration among prospective cohort studies that follow participants for a range of outcomes and perform metabolomic profiling of individuals.

  9. [Application and research advances of metabolomics in the field of orthopedics].

    Science.gov (United States)

    Sun, Zhijian; Qiu, Guixing; Zhao, Yu

    2015-06-01

    Metabolomics is a subject of systematic, qualitative and quantitative analysis of all metabolites in all organisms, which is applied to finding biomarkers and studying pathogenesis of diseases. Study procedures of metabolomics include data acquisition by spectroscopic/spectrometric techniques, multivariate statistical analysis and projection of the acquired metabolomic information. In recent years, metabolomics have gained popularity in orthopedic field. Metabolomic study of osteoarthritis was firstly conducted and widely developed. Metabolite profiles of different samples, including serum/plasma, urine, synovial fluid and synovial tissue, were studied and dozens of differential metabolites and several disturbed metabolic pathways were found. In addition, metabolomic studies of osteoporosis, ankylosing spondylitis and bone tumors were also conducted, which identified many potential biomarkers and made further understanding of pathogenesis of corresponding disease. However, metabolomic studies in orthopedic field just begin. More orthopedic diseases will be researched thank to the satisfactory results of previous reports.

  10. Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

    Science.gov (United States)

    Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat

    2016-01-01

    Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836

  11. Nanoparticle-Assisted Metabolomics

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2018-03-01

    Full Text Available Understanding and harnessing the interactions between nanoparticles and biological molecules is at the forefront of applications of nanotechnology to modern biology. Metabolomics has emerged as a prominent player in systems biology as a complement to genomics, transcriptomics and proteomics. Its focus is the systematic study of metabolite identities and concentration changes in living systems. Despite significant progress over the recent past, important challenges in metabolomics remain, such as the deconvolution of the spectra of complex mixtures with strong overlaps, the sensitive detection of metabolites at low abundance, unambiguous identification of known metabolites, structure determination of unknown metabolites and standardized sample preparation for quantitative comparisons. Recent research has demonstrated that some of these challenges can be substantially alleviated with the help of nanoscience. Nanoparticles in particular have found applications in various areas of bioanalytical chemistry and metabolomics. Their chemical surface properties and increased surface-to-volume ratio endows them with a broad range of binding affinities to biomacromolecules and metabolites. The specific interactions of nanoparticles with metabolites or biomacromolecules help, for example, simplify metabolomics spectra, improve the ionization efficiency for mass spectrometry or reveal relationships between spectral signals that belong to the same molecule. Lessons learned from nanoparticle-assisted metabolomics may also benefit other emerging areas, such as nanotoxicity and nanopharmaceutics.

  12. Metabolomics in Immunology Research.

    Science.gov (United States)

    Everts, Bart

    2018-01-01

    There is a growing appreciation that metabolic processes and individual metabolites can shape the function of immune cells and thereby play important roles in the outcome of immune responses. In this respect, the use of MS- and NMR spectroscopy-based platforms to characterize and quantify metabolites in biological samples has recently yielded important novel insights into how our immune system functions and has contributed to the identification of biomarkers for immune-mediated diseases. Here, these recent immunological studies in which metabolomics has been used and made significant contributions to these fields will be discussed. In particular the role of metabolomics to the rapidly advancing field of cellular immunometabolism will be highlighted as well as the future prospects of such metabolomic tools in immunology.

  13. Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Alonso, Cristina; Fernández-Ramos, David; Varela-Rey, Marta; Martínez-Arranz, Ibon; Navasa, Nicolás; Van Liempd, Sebastiaan M; Lavín Trueba, José L; Mayo, Rebeca; Ilisso, Concetta P; de Juan, Virginia G; Iruarrizaga-Lejarreta, Marta; delaCruz-Villar, Laura; Mincholé, Itziar; Robinson, Aaron; Crespo, Javier; Martín-Duce, Antonio; Romero-Gómez, Manuel; Sann, Holger; Platon, Julian; Van Eyk, Jennifer; Aspichueta, Patricia; Noureddin, Mazen; Falcón-Pérez, Juan M; Anguita, Juan; Aransay, Ana M; Martínez-Chantar, María Luz; Lu, Shelly C; Mato, José M

    2017-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis. We collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis. Livers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice. In an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be

  14. Metabolomics of forage plants: a review.

    Science.gov (United States)

    Rasmussen, Susanne; Parsons, Anthony J; Jones, Christopher S

    2012-11-01

    Forage plant breeding is under increasing pressure to deliver new cultivars with improved yield, quality and persistence to the pastoral industry. New innovations in DNA sequencing technologies mean that quantitative trait loci analysis and marker-assisted selection approaches are becoming faster and cheaper, and are increasingly used in the breeding process with the aim to speed it up and improve its precision. High-throughput phenotyping is currently a major bottle neck and emerging technologies such as metabolomics are being developed to bridge the gap between genotype and phenotype; metabolomics studies on forages are reviewed in this article. Major challenges for pasture production arise from the reduced availability of resources, mainly water, nitrogen and phosphorus, and metabolomics studies on metabolic responses to these abiotic stresses in Lolium perenne and Lotus species will be discussed here. Many forage plants can be associated with symbiotic microorganisms such as legumes with nitrogen fixing rhizobia, grasses and legumes with phosphorus-solubilizing arbuscular mycorrhizal fungi, and cool temperate grasses with fungal anti-herbivorous alkaloid-producing Neotyphodium endophytes and metabolomics studies have shown that these associations can significantly affect the metabolic composition of forage plants. The combination of genetics and metabolomics, also known as genetical metabolomics can be a powerful tool to identify genetic regions related to specific metabolites or metabolic profiles, but this approach has not been widely adopted for forages yet, and we argue here that more studies are needed to improve our chances of success in forage breeding. Metabolomics combined with other '-omics' technologies and genome sequencing can be invaluable tools for large-scale geno- and phenotyping of breeding populations, although the implementation of these approaches in forage breeding programmes still lags behind. The majority of studies using metabolomics

  15. Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network Cohort

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    Kaveri S. Parker

    2016-05-01

    Full Text Available Interstitial cystitis/bladder pain syndrome (IC/BPS is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S, a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS.

  16. DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression.

    Science.gov (United States)

    Torres-Rendon, A; Stewart, R; Craig, G T; Wells, M; Speight, P M

    2009-06-01

    Abnormal DNA content (aneuploidy) has been associated with malignant and premalignant epithelial lesions. The presence of aneuploidy in tumours at an early stage and in dysplastic lesions suggests that analysis of DNA content may be a useful marker for determination of prognosis in these lesions. The aim of this study was to use DNA image cytometry to evaluate aneuploidy in oral dysplastic lesions and to determine whether aneuploidy is associated with malignant progression. Forty-two lesions of oral epithelial dysplasias (OED) that had progressed to oral squamous cell carcinoma (OSCC) and 44 lesions that did not progress were analysed for DNA ploidy using image cytometry of nuclear monolayers prepared from paraffin-embedded tissue. Forty-two OSCC that had arisen from the OED cases and five samples of normal oral mucosa samples (NOM) were also examined. Aneuploidy was found in 14/42 (33.3%) of the OED that progressed, but in only 5/44 (11.3%) of OED that did not progress (p=0.01). A total of 19 OED were aneuploid of which 74% showed malignant progression compared to only 42% of the diploid lesions. The sensitivity and specificity of DNA image cytometry to detect cases with high risk of malignant progression was 0.33 and 0.88, respectively. The PPV and NPV were 0.74 and 0.58. We conclude that aneuploid oral dysplastic lesions have a high risk of malignant progression and that DNA image cytometry might help to identify those lesions most at risk.

  17. Urinary NMR-based metabolomic analysis of rats possessing variable sperm count following orally administered Eurycoma longifolia extracts of different quassinoid levels.

    Science.gov (United States)

    Ebrahimi, Forough; Ibrahim, Baharudin; Teh, Chin-Hoe; Murugaiyah, Vikneswaran; Chan, Kit-Lam

    2016-04-22

    Eurycoma longifolia (Tongkat Ali, TA) roots have been ethnically used as a remedy to boost male sexual desire, libido, energy and fertility. The study evaluated the effect of TA extracts with different quassinoid levels on rats sperm count and examined corresponding post-treatment urinary metabolic changes. Twenty-four male Sprague-Dawley rats, categorized into 4 groups of 6 rats each, were orally administered for 48 days with water for the control (group 1), 125mg/kg of TA water extract (TAW, group 2), 125mg/kg of TA quassinoid-poor extract (TAQP, group 3) and 21mg/kg of TA quassinoid-rich extract (TAQR, group 4). Upon completion of the 48-day treatment, the urine samples were analyzed by NMR and the animals were subsequently sacrificed for sperm count analysis. The urine profiles were categorized according to sperm count level. The results showed that the sperm count in TAW- and TAQR-treated groups was significantly higher compared to the TAQP-administered and control groups. The orthogonal partial least squares discriminant analysis (OPLS-DA) model indicated a clear separation among the urine profiles with respect to sperm count level. Urine (1)H-NMR profiles of the high-sperm count group contained higher concentrations of trigonelline, alanine, benzoic acid and higher intensity of a signal at 3.42ppm, while ethanol was at higher concentration in the normal-sperm count group. The results proved the efficacy of quassinoids on sperm count increase in rats and provided quantitative markers in urine suitable for analysis of sperm profile and male fertility status. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Effect of glycine nitrogen on lettuce growth under soilless culture: a metabolomics approach to identify the main changes occurred in plant primary and secondary metabolism.

    Science.gov (United States)

    Yang, Xiao; Feng, Lei; Zhao, Li; Liu, Xiaosong; Hassani, Danial; Huang, Danfeng

    2018-01-01

    Lettuce is a significant source of antioxidants and bioactive compounds. Nitrate is a cardinal fertilizer in horticulture and influences vegetable yield and quality; however, the negative effects of nitrate on the biosynthesis of flavonoids require further study. It is expected that using fertilizers containing organic nitrogen (N) could promote the synthesis of health-promoting compounds. Lettuces were hydroponically cultured in media containing 9 mmol L -1 nitrate or 9 mmol L -1 glycine for 4 weeks. Primary and secondary metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and ultra-performance liquid chromatography/ion mobility spectrometry/quadrupole time-of-flight mass spectrometry (UPLC/IMS/QTOF-MS). Data analysis revealed that 29 metabolites were significantly altered between nitrate and glycine treatments. Metabolites were tentatively identified by comparison with online databases, literature and standards and using collision cross-section values. Significant differences in flavonoid biosynthesis, phenolic biosynthesis and the tricarboxylic acid (TCA) cycle response were observed between N sources. Compared with nitrate, glycine promoted accumulation of glycosylated flavonoids (quercetin 3-glucoside, quercetin 3-(6″-malonyl-glucoside), luteolin 7-glucuronide, luteolin 7-glucoside), ascorbic acid and amino acids (l-valine, l-leucine, l-glutamine, asparagine, l-serine, l-ornithine, 4-aminobutanoic acid, l-phenylalanine) but reduced phenolic acids (dihydroxybenzoic acid hexose isomers 1 and 2, chicoric acid, chicoric acid isomer 1) and TCA intermediates (fumaric, malic, citric and succinic acids). The novel methodology applied in this study can be used to characterize metabolites in lettuce. Accumulation of glycosylated flavonoids, amino acids and ascorbic acid in response to glycine supply provides strong evidence supporting the idea that using amino acids as an N source alters the nutritional value of vegetable crops. © 2017

  19. Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality.

    Directory of Open Access Journals (Sweden)

    Johannes Raffler

    2015-09-01

    Full Text Available Genome-wide association studies with metabolic traits (mGWAS uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3. Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13, pulmonary hypertension (CPS1, and ischemic stroke (XYLB. By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular

  20. Oral peanut challenge identifies an allergy but the peanut allergen threshold sensitivity is not reproducible.

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    Susanne Glaumann

    Full Text Available BACKGROUND: Double-blind placebo-controlled food challenge, DBPCFC, the gold standard for diagnosing food allergy, is time-consuming and potentially dangerous. A basophil allergen threshold sensitivity test, CD-sens, has shown promising results as a diagnostic tool in food allergy. OBJECTIVES: To evaluate the reproducibility of oral peanut challenge and compare the outcome to CD-sens in peanut-sensitized children. METHODS: Twenty-seven children (4-19 years underwent a DBPCFC followed by a single-blind oral food-challenge. The peanut challenges (1 mg to 5 g were evaluated by severity scoring. Blood samples were drawn for CD-sens before the two first challenges. RESULTS: Thirteen children (48% did not react at any of the challenges. Fourteen reacted at both peanut challenges but not to placebo. Only two of these children reacted at the same threshold dose and with the same severity score. All other children scored differently or reacted at different doses. For children with a positive challenge the geometric mean of the ratio of the doses was 1.834 (p = 0.307 and the arithmetic mean of the difference between the severity scores was 0.143 (p = 0.952. No association was obtained between the two peanut challenges regarding severity score (r(s = 0.11, p = 0.71 or threshold dose (r(s = 0.35, p = 0.22. Among the children positive in peanut challenge, 12 were positive in CD-sens. Two were low-responders and could not be evaluated. Geometric mean of the ratio of CD-sens values in children with a positive challenge was 1.035 (p = 0.505 but unlike for the severity score and the threshold dose the association between the two CD-sens values was strong (r(s = 0.94, P<0.001. CONCLUSIONS: For a positive/negative test the reproducibility is 100% for both peanut challenge and CD-sens. However, a comparison of the degree of allergen threshold sensitivity between the two tests is not possible since the threshold dose and severity

  1. Integrated genomic analyses identify KDM1A's role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer.

    Science.gov (United States)

    Narayanan, Sathiya Pandi; Singh, Smriti; Gupta, Amit; Yadav, Sandhya; Singh, Shree Ram; Shukla, Sanjeev

    2015-10-28

    The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silico pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. H-classic: a new method to identify classic articles in Implant Dentistry, Periodontics, and Oral Surgery.

    Science.gov (United States)

    De la Flor-Martínez, Maria; Galindo-Moreno, Pablo; Sánchez-Fernández, Elena; Piattelli, Adriano; Cobo, Manuel Jesus; Herrera-Viedma, Enrique

    2016-10-01

    The study of classic papers permits analysis of the past, present, and future of a specific area of knowledge. This type of analysis is becoming more frequent and more sophisticated. Our objective was to use the H-classics method, based on the h-index, to analyze classic papers in Implant Dentistry, Periodontics, and Oral Surgery (ID, P, and OS). First, an electronic search of documents related to ID, P, and OS was conducted in journals indexed in Journal Citation Reports (JCR) 2014 within the category 'Dentistry, Oral Surgery & Medicine'. Second, Web of Knowledge databases were searched using Mesh terms related to ID, P, and OS. Finally, the H-classics method was applied to select the classic articles in these disciplines, collecting data on associated research areas, document type, country, institutions, and authors. Of 267,611 documents related to ID, P, and OS retrieved from JCR journals (2014), 248 were selected as H-classics. They were published in 35 journals between 1953 and 2009, most frequently in the Journal of Clinical Periodontology (18.95%), the Journal of Periodontology (18.54%), International Journal of Oral and Maxillofacial Implants (9.27%), and Clinical Oral Implant Research (6.04%). These classic articles derived from the USA in 49.59% of cases and from Europe in 47.58%, while the most frequent host institution was the University of Gothenburg (17.74%) and the most frequent authors were J. Lindhe (10.48%) and S. Socransky (8.06%). The H-classics approach offers an objective method to identify core knowledge in clinical disciplines such as ID, P, and OS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Stimulation of oral fibroblast chemokine receptors identifies CCR3 and CCR4 as potential wound healing targets

    Science.gov (United States)

    Buskermolen, Jeroen K.; Roffel, Sanne

    2017-01-01

    The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts. Twelve of these fourteen chemokines stimulated gingiva fibroblast migration (all except for CXCL8 and CXCL12). Five of the chemokines stimulated proliferation (CCL5/CCR3, CCL15/CCR3, CCL22/CCR4, CCL28/CCR3/CCR10, and XCL1/XCR1). Furthermore, CCL28/CCR3/CCR10 and CCL22/CCR4 stimulation increased IL‐6 secretion and CCL28/CCR3/CCR10 together with CCL27/CCR10 upregulated HGF secretion. Moreover, TIMP‐1 secretion was reduced by CCL15/CCR3. In conclusion, this in‐vitro study identifies chemokine receptor‐ligand pairs which may be used in future targeted wound healing strategies. In particular, we identified the chemokine receptors CCR3 and CCR4, and the mucosa specific chemokine CCL28, as having an predominant role in oral wound healing by increasing human gingiva fibroblast proliferation, migration, and the secretion of IL‐6 and HGF and reducing the secretion of TIMP‐1. PMID:28387445

  4. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

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    Daniel Belstrøm

    2016-09-01

    Full Text Available Background The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Methods Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. Results We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Conclusions Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity.

  5. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

    International Nuclear Information System (INIS)

    Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

    2011-01-01

    Research highlights: → We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. → 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. → 12 Gy induced significant histopathologic changes and cellular apoptosis. → 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first

  6. Microbial metabolomics : Toward a platform with full metabolome coverage

    NARCIS (Netherlands)

    Werf, M.J.v.d.; Overkamp, K.M.; Muilwijk, B.; Coulier, L.; Hankemeier, T.

    2007-01-01

    Achieving metabolome data with satisfactory coverage is a formidable challenge in metabolomics because metabolites are a chemically highly diverse group of compounds. Here we present a strategy for the development of an advanced analytical platform that allows the comprehensive analysis of microbial

  7. Impact of dietary polydextrose fiber on the human gut metabolome.

    Science.gov (United States)

    Lamichhane, Santosh; Yde, Christian C; Forssten, Sofia; Ouwehand, Arthur C; Saarinen, Markku; Jensen, Henrik Max; Gibson, Glenn R; Rastall, Robert; Fava, Francesca; Bertram, Hanne Christine

    2014-10-08

    The aim of the present study was to elucidate the impact of polydextrose PDX an soluble fiber, on the human fecal metabolome by high-resolution nuclear magnetic resonance (NMR) spectroscopy-based metabolomics in a dietary intervention study (n = 12). Principal component analysis (PCA) revealed a strong effect of PDX consumption on the fecal metabolome, which could be mainly ascribed to the presence of undigested fiber and oligosaccharides formed from partial degradation of PDX. Our results demonstrate that NMR-based metabolomics is a useful technique for metabolite profiling of feces and for testing compliance to dietary fiber intake in such trials. In addition, novel associations between PDX and the levels of the fecal metabolites acetate and propionate could be identified. The establishment of a correlation between the fecal metabolome and levels of Bifidobacterium (R(2) = 0.66) and Bacteroides (R(2) = 0.46) demonstrates the potential of NMR-based metabolomics to elucidate metabolic activity of bacteria in the gut.

  8. Mass spectrometry-based metabolomics for tuberculosis meningitis.

    Science.gov (United States)

    Zhang, Peixu; Zhang, Weiguanliu; Lang, Yue; Qu, Yan; Chu, Fengna; Chen, Jiafeng; Cui, Li

    2018-04-18

    Tuberculosis meningitis (TBM) is a prevalent form of extra-pulmonary tuberculosis that causes substantial morbidity and mortality. Diagnosis of TBM is difficult because of the limited sensitivity of existing laboratory techniques. A metabolomics approach can be used to investigate the sets of metabolites of both bacteria and host, and has been used to clarify the mechanisms underlying disease development, and identify metabolic changes, leadings to improved methods for diagnosis, treatment, and prognostication. Mass spectrometry (MS) is a major analysis platform used in metabolomics, and MS-based metabolomics provides wide metabolite coverage, because of its high sensitivity, and is useful for the investigation of Mycobacterium tuberculosis (Mtb) and related diseases. It has been used to investigate TBM diagnosis; however, the processes involved in the MS-based metabolomics approach are complex and flexible, and often consist of several steps, and small changes in the methods used can have a huge impact on the final results. Here, the process of MS-based metabolomics is summarized and its applications in Mtb and Mtb-related diseases discussed. Moreover, the current status of TBM metabolomics is described. Copyright © 2018. Published by Elsevier B.V.

  9. SMART: Statistical Metabolomics Analysis-An R Tool.

    Science.gov (United States)

    Liang, Yu-Jen; Lin, Yu-Ting; Chen, Chia-Wei; Lin, Chien-Wei; Chao, Kun-Mao; Pan, Wen-Harn; Yang, Hsin-Chou

    2016-06-21

    Metabolomics data provide unprecedented opportunities to decipher metabolic mechanisms by analyzing hundreds to thousands of metabolites. Data quality concerns and complex batch effects in metabolomics must be appropriately addressed through statistical analysis. This study developed an integrated analysis tool for metabolomics studies to streamline the complete analysis flow from initial data preprocessing to downstream association analysis. We developed Statistical Metabolomics Analysis-An R Tool (SMART), which can analyze input files with different formats, visually represent various types of data features, implement peak alignment and annotation, conduct quality control for samples and peaks, explore batch effects, and perform association analysis. A pharmacometabolomics study of antihypertensive medication was conducted and data were analyzed using SMART. Neuromedin N was identified as a metabolite significantly associated with angiotensin-converting-enzyme inhibitors in our metabolome-wide association analysis (p = 1.56 × 10(-4) in an analysis of covariance (ANCOVA) with an adjustment for unknown latent groups and p = 1.02 × 10(-4) in an ANCOVA with an adjustment for hidden substructures). This endogenous neuropeptide is highly related to neurotensin and neuromedin U, which are involved in blood pressure regulation and smooth muscle contraction. The SMART software, a user guide, and example data can be downloaded from http://www.stat.sinica.edu.tw/hsinchou/metabolomics/SMART.htm .

  10. Comparative Genomics of the Genus Porphyromonas Identifies Adaptations for Heme Synthesis within the Prevalent Canine Oral Species Porphyromonas cangingivalis.

    Science.gov (United States)

    O'Flynn, Ciaran; Deusch, Oliver; Darling, Aaron E; Eisen, Jonathan A; Wallis, Corrin; Davis, Ian J; Harris, Stephen J

    2015-11-13

    Porphyromonads play an important role in human periodontal disease and recently have been shown to be highly prevalent in canine mouths. Porphyromonas cangingivalis is the most prevalent canine oral bacterial species in both plaque from healthy gingiva and plaque from dogs with early periodontitis. The ability of P. cangingivalis to flourish in the different environmental conditions characterized by these two states suggests a degree of metabolic flexibility. To characterize the genes responsible for this, the genomes of 32 isolates (including 18 newly sequenced and assembled) from 18 Porphyromonad species from dogs, humans, and other mammals were compared. Phylogenetic trees inferred using core genes largely matched previous findings; however, comparative genomic analysis identified several genes and pathways relating to heme synthesis that were present in P. cangingivalis but not in other Porphyromonads. Porphyromonas cangingivalis has a complete protoporphyrin IX synthesis pathway potentially allowing it to synthesize its own heme unlike pathogenic Porphyromonads such as Porphyromonas gingivalis that acquire heme predominantly from blood. Other pathway differences such as the ability to synthesize siroheme and vitamin B12 point to enhanced metabolic flexibility for P. cangingivalis, which may underlie its prevalence in the canine oral cavity. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry

    International Nuclear Information System (INIS)

    Spur, Eva-Margarete; Decelle, Emily A.; Cheng, Leo L.

    2013-01-01

    Metabolomic imaging of prostate cancer (PCa) aims to improve in vivo imaging capability so that PCa tumors can be localized noninvasively to guide biopsy and evaluated for aggressiveness prior to prostatectomy, as well as to assess and monitor PCa growth in patients with asymptomatic PCa newly diagnosed by biopsy. Metabolomics studies global variations of metabolites with which malignancy conditions can be evaluated by profiling the entire measurable metabolome, instead of focusing only on certain metabolites or isolated metabolic pathways. At present, PCa metabolomics is mainly studied by magnetic resonance spectroscopy (MRS) and mass spectrometry (MS). With MRS imaging, the anatomic image, obtained from magnetic resonance imaging, is mapped with values of disease condition-specific metabolomic profiles calculated from MRS of each location. For example, imaging of removed whole prostates has demonstrated the ability of metabolomic profiles to differentiate cancerous foci from histologically benign regions. Additionally, MS metabolomic imaging of prostate biopsies has uncovered metabolomic expression patterns that could discriminate between PCa and benign tissue. Metabolomic imaging offers the potential to identify cancer lesions to guide prostate biopsy and evaluate PCa aggressiveness noninvasively in vivo, or ex vivo to increase the power of pathology analysis. Potentially, this imaging ability could be applied not only to PCa, but also to different tissues and organs to evaluate other human malignancies and metabolic diseases. (orig.)

  12. Exploring the inflammatory metabolomic profile to predict response to TNF-α inhibitors in rheumatoid arthritis

    NARCIS (Netherlands)

    Cuppen, B.V.J.; Fu, J.; Wietmarschen, H.A. van; Harms, A.C.; Koval, S.; Marijnissen, A.C.A.; Peeters, J.J.W.; Bijlsma, J.W.J.; Tekstra, J.; Laar, J.M. van; Hankemeier, T.; Lafeber, F.P.J.G.; Greef, J. van der

    2016-01-01

    In clinical practice, approximately one-Third of patients with rheumatoid arthritis(RA) respond insufficiently to TNF-α inhibitors (TNFis). The aim of the study was to explore the use of a metabolomics to identify predictors for the outcome of TNFi therapy, and study the metabolomic fingerprint in

  13. Introducing Undergraduate Students to Metabolomics Using a NMR-Based Analysis of Coffee Beans

    Science.gov (United States)

    Sandusky, Peter Olaf

    2017-01-01

    Metabolomics applies multivariate statistical analysis to sets of high-resolution spectra taken over a population of biologically derived samples. The objective is to distinguish subpopulations within the overall sample population, and possibly also to identify biomarkers. While metabolomics has become part of the standard analytical toolbox in…

  14. An untargeted global metabolomic analysis reveals the biochemical changes underlying basal resistance and priming in Solanum lycopersicum, and identifies 1-methyltryptophan as a metabolite involved in plant responses to Botrytis cinerea and Pseudomonas syringae.

    Science.gov (United States)

    Camañes, Gemma; Scalschi, Loredana; Vicedo, Begonya; González-Bosch, Carmen; García-Agustín, Pilar

    2015-10-01

    In this study, we have used untargeted global metabolomic analysis to determine and compare the chemical nature of the metabolites altered during the infection of tomato plants (cv. Ailsa Craig) with Botrytis cinerea (Bot) or Pseudomonas syringae pv. tomato DC3000 (Pst), pathogens that have different invasion mechanisms and lifestyles. We also obtained the metabolome of tomato plants primed using the natural resistance inducer hexanoic acid and then infected with these pathogens. By contrasting the metabolomic profiles of infected, primed, and primed + infected plants, we determined not only the processes or components related directly to plant defense responses, but also inferred the metabolic mechanisms by which pathogen resistance is primed. The data show that basal resistance and hexanoic acid-induced resistance to Bot and Pst are associated with a marked metabolic reprogramming. This includes significant changes in amino acids, sugars and free fatty acids, and in primary and secondary metabolism. Comparison of the metabolic profiles of the infections indicated clear differences, reflecting the fact that the plant's chemical responses are highly adapted to specific attackers. The data also indicate involvement of signaling molecules, including pipecolic and azelaic acids, in response to Pst and, interestingly, to Bot. The compound 1-methyltryptophan was shown to be associated with the tomato-Pst and tomato-Bot interactions as well as with hexanoic acid-induced resistance. Root application of this Trp-derived metabolite also demonstrated its ability to protect tomato plants against both pathogens. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  15. The Use of Oral Histories to Identify Criteria for Future Scenarios of Sustainable Farming in the South Yangtze River, China

    Directory of Open Access Journals (Sweden)

    Pingyang Liu

    2016-08-01

    Full Text Available Agricultural practices in Jiangnan water towns have historically been identified as maintaining a balance between human activity and the local environment, but are now a significant local source of water pollution. Using a multi-methods approach, this study deduces the environmental impact of traditional practices, and the socially desired conditions for successfully reintroducing critical ones. Oral histories from 31 farmers in Tianshanzhuang village, South Yangtze River were in order to chart changes in farming practices over four historic periods, and used to estimate the nitrogen and phosphorus burdens per acre. Findings show that the use of Lan River Mud—dredged mud for fertilizer—was key in producing a positive impact, but abandoned after the 1980s. Four criteria hindering reintroduction of traditional practices were identified, and potentially useful but fragmented emerging local candidate practices are considered against these, as are recent practices in Japan. We propose that the cooperation of several stakeholders with various related government departments in China could lead to a portfolio of effective policy changes and should be studied further: to include new methods and uses of Lan River Mud; the integration of aquaculture, leisure and tourism industries with agriculture; and the production of organic produce with well-planned internet-linked sales, delivery and coordination mechanisms.

  16. Metabolomics for assessment of nutritional status.

    Science.gov (United States)

    Zivkovic, Angela M; German, J Bruce

    2009-09-01

    The current rise in diet-related diseases continues to be one of the most significant health problems facing both the developed and the developing world. The use of metabolomics - the accurate and comprehensive measurement of a significant fraction of important metabolites in accessible biological fluids - for the assessment of nutritional status is a promising way forward. The basic toolset, targets and knowledge are all being developed in the emerging field of metabolomics, yet important knowledge and technology gaps will need to be addressed in order to bring such assessment to practice. Dysregulation within the principal metabolic organs (e.g. intestine, adipose, skeletal muscle and liver) are at the center of a diet-disease paradigm that includes metabolic syndrome, type 2 diabetes and obesity. The assessment of both essential nutrient status and the more comprehensive systemic metabolic response to dietary, lifestyle and environmental influences (e.g. metabolic phenotype) are necessary for the evaluation of status in individuals that can identify the multiple targets of intervention needed to address metabolic disease. The first proofs of principle building the knowledge to bring actionable metabolic diagnostics to practice through metabolomics are now appearing.

  17. Metabolomics of Genetically Modified Crops

    Directory of Open Access Journals (Sweden)

    Carolina Simó

    2014-10-01

    Full Text Available Metabolomic-based approaches are increasingly applied to analyse genetically modified organisms (GMOs making it possible to obtain broader and deeper information on the composition of GMOs compared to that obtained from traditional analytical approaches. The combination in metabolomics of advanced analytical methods and bioinformatics tools provides wide chemical compositional data that contributes to corroborate (or not the substantial equivalence and occurrence of unintended changes resulting from genetic transformation. This review provides insight into recent progress in metabolomics studies on transgenic crops focusing mainly in papers published in the last decade.

  18. Metabolomics of genetically modified crops.

    Science.gov (United States)

    Simó, Carolina; Ibáñez, Clara; Valdés, Alberto; Cifuentes, Alejandro; García-Cañas, Virginia

    2014-10-20

    Metabolomic-based approaches are increasingly applied to analyse genetically modified organisms (GMOs) making it possible to obtain broader and deeper information on the composition of GMOs compared to that obtained from traditional analytical approaches. The combination in metabolomics of advanced analytical methods and bioinformatics tools provides wide chemical compositional data that contributes to corroborate (or not) the substantial equivalence and occurrence of unintended changes resulting from genetic transformation. This review provides insight into recent progress in metabolomics studies on transgenic crops focusing mainly in papers published in the last decade.

  19. Metabolomics of Genetically Modified Crops

    Science.gov (United States)

    Simó, Carolina; Ibáñez, Clara; Valdés, Alberto; Cifuentes, Alejandro; García-Cañas, Virginia

    2014-01-01

    Metabolomic-based approaches are increasingly applied to analyse genetically modified organisms (GMOs) making it possible to obtain broader and deeper information on the composition of GMOs compared to that obtained from traditional analytical approaches. The combination in metabolomics of advanced analytical methods and bioinformatics tools provides wide chemical compositional data that contributes to corroborate (or not) the substantial equivalence and occurrence of unintended changes resulting from genetic transformation. This review provides insight into recent progress in metabolomics studies on transgenic crops focusing mainly in papers published in the last decade. PMID:25334064

  20. Molecular biological change in oral cancer, summary of our researches

    Directory of Open Access Journals (Sweden)

    Nobuharu Yamamoto, DDS, PhD

    2015-02-01

    Full Text Available Molecular biological search and identification of cancer have a variety of clinical significance. Microarray, proteomics and metabolome analyses are powerful analytical methods for rapid screening of tumor markers. From the results, it was revealed that a number of genes are specifically expressed in oral cancers. From the results of CAN and LOH analyses of the entire genome, three candidate gene loci (D1S1189, D1S2151, D1S2595 were identified on 1q31.1 region. From the results obtained by using array CGH, amplification of the 11q13 regions was observed in 30% of the group with lymph node metastasis, and a numbers of genes were located in the 11q13 regions, in which increase of the copy number was observed in only the group with lymph node metastasis. From the results of proteomics analysis, three protein spots, in which expression increased in a common manner with a oral cancer cell line, as well as 27 spots, in which expression decreased in a common manner with a oral cancer cell line, were identified from these cataloged spots. Seven spots of proteins that are specifically expressed in the whole saliva of oral cancer patients before a surgery and not detected from the whole saliva after the surgery or the whole saliva of a healthy subject were selected. In the metabolome analysis, peaks of 250 of the major metabolic substances (136 cations, 114 anions were detected.

  1. Evaluation of cadmium-induced nephrotoxicity using urinary metabolomic profiles in sprague-dawley male rats.

    Science.gov (United States)

    Lee, Yu Kyung; Park, Eun Young; Kim, Shiwon; Son, Ji Yeon; Kim, Tae Hyung; Kang, Won Gu; Jeong, Tae Chun; Kim, Kyu-Bong; Kwack, Seung Jun; Lee, Jaewon; Kim, Suhkmann; Lee, Byung-Mu; Kim, Hyung Sik

    2014-01-01

    The aim of this study was to investigate urinary metabolomic profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution (1)H-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citrate, serine, 3-hydroxyisovalerate, 4-hydroxyphenyllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phenylalanine and carbohydrate (glucose) were altered in urine after CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellular mechanism underlying Cd-induced renal injury in humans.

  2. Metabolomic-based identification of clusters that reflect dietary patterns.

    Science.gov (United States)

    Gibbons, Helena; Carr, Eibhlin; McNulty, Breige A; Nugent, Anne P; Walton, Janette; Flynn, Albert; Gibney, Michael J; Brennan, Lorraine

    2017-10-01

    Classification of subjects into dietary patterns generally relies on self-reporting dietary data which are prone to error. The aim of the present study was to develop a model for objective classification of people into dietary patterns based on metabolomic data. Dietary and urinary metabolomic data from the National Adult Nutrition Survey (NANS) was used in the analysis (n = 567). Two-step cluster analysis was applied to the urinary data to identify clusters. The subsequent model was used in an independent cohort to classify people into dietary patterns. Two distinct dietary patterns were identified. Cluster 1 was characterized by significantly higher intakes of breakfast cereals, low fat and skimmed milks, potatoes, fruit, fish and fish dishes (p patterns based on metabolomics data. Future applications of this approach could be developed for rapid and objective assignment of subjects into dietary patterns. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    Energy Technology Data Exchange (ETDEWEB)

    Bag, Swarnendu, E-mail: Swarna.bag@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Banerjee, Deb Ranjan, E-mail: debranjan2@gmail.com [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Basak, Amit, E-mail: absk@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Das, Amit Kumar, E-mail: amitk@hijli.iitkgp.ernet.in [Department of Biotechnology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Pal, Mousumi, E-mail: drmpal62@gmail.com [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Banerjee, Rita, E-mail: ritabanerjee@outlook.com [Department of Science and Technology, New Mehrauli Road, New Delhi 110016 (India); Paul, Ranjan Rashmi, E-mail: dr_rsspaul@yahoo.co.in [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Chatterjee, Jyotirmoy, E-mail: jchatterjee.iitkgp@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India)

    2015-04-17

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.

  4. Deconstructing the pig sex metabolome: Targeted metabolomics in heavy pigs revealed sexual dimorphisms in plasma biomarkers and metabolic pathways.

    Science.gov (United States)

    Bovo, S; Mazzoni, G; Calò, D G; Galimberti, G; Fanelli, F; Mezzullo, M; Schiavo, G; Scotti, E; Manisi, A; Samoré, A B; Bertolini, F; Trevisi, P; Bosi, P; Dall'Olio, S; Pagotto, U; Fontanesi, L

    2015-12-01

    Metabolomics has opened new possibilities to investigate metabolic differences among animals. In this study, we applied a targeted metabolomic approach to deconstruct the pig sex metabolome as defined by castrated males and entire gilts. Plasma from 545 performance-tested Italian Large White pigs (172 castrated males and 373 females) sampled at about 160 kg live weight were analyzed for 186 metabolites using the Biocrates AbsoluteIDQ p180 Kit. After filtering, 132 metabolites (20 AA, 11 biogenic amines, 1 hexose, 13 acylcarnitines, 11 sphingomyelins, 67 phosphatidylcholines, and 9 lysophosphatidylcholines) were retained for further analyses. The multivariate approach of the sparse partial least squares discriminant analysis was applied, together with a specifically designed statistical pipeline, that included a permutation test and a 10 cross-fold validation procedure that produced stability and effect size statistics for each metabolite. Using this approach, we identified 85 biomarkers (with metabolites from all analyzed chemical families) that contributed to the differences between the 2 groups of pigs ( metabolic shift in castrated males toward energy storage and lipid production. Similar general patterns were observed for most sphingomyelins, phosphatidylcholines, and lysophosphatidylcholines. Metabolomic pathway analysis and pathway enrichment identified several differences between the 2 sexes. This metabolomic overview opened new clues on the biochemical mechanisms underlying sexual dimorphism that, on one hand, might explain differences in terms of economic traits between castrated male pigs and entire gilts and, on the other hand, could strengthen the pig as a model to define metabolic mechanisms related to fat deposition.

  5. Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Hansen, Claus; Reibel, Jesper

    2010-01-01

    Lichenoid drug eruptions (LDE) in the oral cavity are adverse drug reactions (ADR) that are impossible to differentiate from oral lichen planus (OLP) as no phenotypic criteria exist. Impaired function of polymorphic cytochrome 450-enzymes (CYPs) may cause increased plasma concentration of some...

  6. NMR-based milk metabolomics

    DEFF Research Database (Denmark)

    Sundekilde, Ulrik; Larsen, Lotte Bach; Bertram, Hanne Christine S.

    2013-01-01

    and processing capabilities of bovine milk is closely associated to milk composition. Metabolomics is ideal in the study of the low-molecular-weight compounds in milk, and this review focuses on the recent nuclear magnetic resonance (NMR)-based metabolomics trends in milk research, including applications linking...... the milk metabolite profiling with nutritional aspects, and applications which aim to link the milk metabolite profile to various technological qualities of milk. The metabolite profiling studies encompass the identification of novel metabolites, which potentially can be used as biomarkers or as bioactive...... compounds. Furthermore, metabolomics applications elucidating how the differential regulated genes affects milk composition are also reported. This review will highlight the recent advances in NMR-based metabolomics on milk, as well as give a brief summary of when NMR spectroscopy can be useful for gaining...

  7. Metabolomics Workbench (MetWB)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Metabolomics Program's Data Repository and Coordinating Center (DRCC), housed at the San Diego Supercomputer Center (SDSC), University of California, San Diego,...

  8. LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS.

    Science.gov (United States)

    Yuan, Yao; Xie, Xiaoyan; Jiang, Yuchen; Wei, Zihao; Wang, Peiqi; Chen, Fangman; Li, Xinyi; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Wang, Zhiyong; Chen, Qianming

    2017-09-07

    Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500 000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distinct proteins were identified with changed expression levels. Among them, LRP6 expression was found to be upregulated in OSCC tissues, and correlated with a cluster of clinicopathologic parameters, including smoking, drinking, tumor differentiation status, lymph node metastasis and survival time. Notably, knockdown of LRP6 inhibited the proliferation ability of OSCC cells. Furthermore, we demonstrated that the expression of LRP6 in OSCC cells is positively correlated with its downstream oncogene, FGF8. The present study suggests that LRP6 could be a potential biomarker for OSCC patients, and might further assist in the therapeutic decisions in OSCC treatment.

  9. Can NMR solve some significant challenges in metabolomics?

    Science.gov (United States)

    Nagana Gowda, G. A.; Raftery, Daniel

    2015-11-01

    The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory.

  10. LC-MS-BASED METABOLOMICS OF XENOBIOTIC-INDUCED TOXICITIES

    Directory of Open Access Journals (Sweden)

    Chi Chen

    2013-01-01

    Full Text Available Xenobiotic exposure, especially high-dose or repeated exposure of xenobiotics, can elicit detrimental effects on biological systems through diverse mechanisms. Changes in metabolic systems, including formation of reactive metabolites and disruption of endogenous metabolism, are not only the common consequences of toxic xenobiotic exposure, but in many cases are the major causes behind development of xenobiotic-induced toxicities (XIT. Therefore, examining the metabolic events associated with XIT generates mechanistic insights into the initiation and progression of XIT, and provides guidance for prevention and treatment. Traditional bioanalytical platforms that target only a few suspected metabolites are capable of validating the expected outcomes of xenobiotic exposure. However, these approaches lack the capacity to define global changes and to identify unexpected events in the metabolic system. Recent developments in high-throughput metabolomics have dramatically expanded the scope and potential of metabolite analysis. Among all analytical techniques adopted for metabolomics, liquid chromatography-mass spectrometry (LC-MS has been most widely used for metabolomic investigations of XIT due to its versatility and sensitivity in metabolite analysis. In this review, technical platform of LC-MS-based metabolomics, including experimental model, sample preparation, instrumentation, and data analysis, are discussed. Applications of LC-MS-based metabolomics in exploratory and hypothesis-driven investigations of XIT are illustrated by case studies of xenobiotic metabolism and endogenous metabolism associated with xenobiotic exposure.

  11. Untargeted Metabolomics To Ascertain Antibiotic Modes of Action

    Science.gov (United States)

    Vincent, Isabel M.; Ehmann, David E.; Mills, Scott D.; Perros, Manos

    2016-01-01

    Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5′-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanide m-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime. Data analysts were blind to the compound identities but managed to identify the target as thymidylate kinase for AZ1, isoprenoid biosynthesis for fosmidomycin, acyl-transferase for CHIR-090, and DNA metabolism for 2-(cyclobutylmethoxy)-5′-deoxyadenosine. Changes to cell wall metabolites were seen in ceftazidime treatments, although other changes, presumably relating to off-target effects, dominated spectral outputs in the untargeted approach. Drugs which do not work through metabolic pathways, such as the proton carrier CCCP, have no discernible impact on the metabolome. The untargeted metabolomics approach also revealed modifications to two compounds, namely, fosmidomycin and AZ7. An untreated control was also analyzed, and changes to the metabolome were seen over 4 h, highlighting the necessity for careful controls in these types of studies. Metabolomics is a useful tool in the analysis of drug modes of action and can complement other technologies already in use. PMID:26833150

  12. Plant Metabolomics: An Indispensable System Biology Tool for Plant Science

    Directory of Open Access Journals (Sweden)

    Jun Hong

    2016-06-01

    Full Text Available As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality.

  13. Plant Metabolomics: An Indispensable System Biology Tool for Plant Science

    Science.gov (United States)

    Hong, Jun; Yang, Litao; Zhang, Dabing; Shi, Jianxin

    2016-01-01

    As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality. PMID:27258266

  14. What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?

    DEFF Research Database (Denmark)

    Gonzalez-Franquesa, Alba; Burkart, Alison M; Isganaitis, Elvira

    2016-01-01

    and mathematical modeling approaches, have provided the scientific community with new tools to describe the T2D metabolome. The metabolomics signatures associated with T2D and obesity include increased levels of lactate, glycolytic intermediates, branched-chain and aromatic amino acids, and long-chain fatty acids......Type 2 diabetes (T2D) is increasing worldwide, making identification of biomarkers for detection, staging, and effective prevention strategies an especially critical scientific and medical goal. Fortunately, advances in metabolomics techniques, together with improvements in bioinformatics....... Conversely, tricarboxylic acid cycle intermediates, betaine, and other metabolites decrease. Future studies will be required to fully integrate these and other findings into our understanding of diabetes pathophysiology and to identify biomarkers of disease risk, stage, and responsiveness to specific...

  15. Metabolomics in epidemiology: from metabolite concentrations to integrative reaction networks.

    Science.gov (United States)

    Fearnley, Liam G; Inouye, Michael

    2016-10-01

    Metabolomics is becoming feasible for population-scale studies of human disease. In this review, we survey epidemiological studies that leverage metabolomics and multi-omics to gain insight into disease mechanisms. We outline key practical, technological and analytical limitations while also highlighting recent successes in integrating these data. The use of multi-omics to infer reaction rates is discussed as a potential future direction for metabolomics research, as a means of identifying biomarkers as well as inferring causality. Furthermore, we highlight established analysis approaches as well as simulation-based methods currently used in single- and multi-cell levels in systems biology. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  16. Plant Metabolomics: An Indispensable System Biology Tool for Plant Science.

    Science.gov (United States)

    Hong, Jun; Yang, Litao; Zhang, Dabing; Shi, Jianxin

    2016-06-01

    As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality.

  17. Metabolomics Society’s International Affiliations

    NARCIS (Netherlands)

    Roessner, U.; Rolin, D.; Rijswijk, van M.E.C.; Hall, R.D.; Hankemeier, T.

    2015-01-01

    In 2012 the Metabolomics Society established a more formal system for national and regional metabolomics initiatives, interest groups, societies and networks to become an International Affiliate of the Society. A number of groups (http://metabolomicssociety.org/international-affilia

  18. Applying psychological theory to evidence-based clinical practice: identifying factors predictive of taking intra-oral radiographs.

    Science.gov (United States)

    Bonetti, Debbie; Pitts, Nigel B; Eccles, Martin; Grimshaw, Jeremy; Johnston, Marie; Steen, Nick; Glidewell, Liz; Thomas, Ruth; Maclennan, Graeme; Clarkson, Jan E; Walker, Anne

    2006-10-01

    This study applies psychological theory to the implementation of evidence-based clinical practice. The first objective was to see if variables from psychological frameworks (developed to understand, predict and influence behaviour) could predict an evidence-based clinical behaviour. The second objective was to develop a scientific rationale to design or choose an implementation intervention. Variables from the Theory of Planned Behaviour, Social Cognitive Theory, Self-Regulation Model, Operant Conditioning, Implementation Intentions and the Precaution Adoption Process were measured, with data collection by postal survey. The primary outcome was the number of intra-oral radiographs taken per course of treatment collected from a central fee claims database. Participants were 214 Scottish General Dental Practitioners. At the theory level, the Theory of Planned Behaviour explained 13% variance in the number of radiographs taken, Social Cognitive Theory explained 7%, Operant Conditioning explained 8%, Implementation Intentions explained 11%. Self-Regulation and Stage Theory did not predict significant variance in radiographs taken. Perceived behavioural control, action planning and risk perception explained 16% of the variance in number of radiographs taken. Knowledge did not predict the number of radiographs taken. The results suggest an intervention targeting predictive psychological variables could increase the implementation of this evidence-based practice, while influencing knowledge is unlikely to do so. Measures which predicted number of radiographs taken also predicted intention to take radiographs, and intention accounted for significant variance in behaviour (adjusted R(2)=5%: F(1,166)=10.28, ptheory-based approach enabled the creation of a methodology that can be replicated for identifying factors predictive of clinical behaviour and for the design and choice of interventions to modify practice as new evidence emerges.

  19. ECMDB: The E. coli Metabolome Database

    OpenAIRE

    Guo, An Chi; Jewison, Timothy; Wilson, Michael; Liu, Yifeng; Knox, Craig; Djoumbou, Yannick; Lo, Patrick; Mandal, Rupasri; Krishnamurthy, Ram; Wishart, David S.

    2012-01-01

    The Escherichia coli Metabolome Database (ECMDB, http://www.ecmdb.ca) is a comprehensively annotated metabolomic database containing detailed information about the metabolome of E. coli (K-12). Modelled closely on the Human and Yeast Metabolome Databases, the ECMDB contains >2600 metabolites with links to ?1500 different genes and proteins, including enzymes and transporters. The information in the ECMDB has been collected from dozens of textbooks, journal articles and electronic databases. E...

  20. Metabolomics: the chemistry between ecology and genetics

    NARCIS (Netherlands)

    Macel, M.; Dam, van N.M.; Keurentjes, J.J.B.

    2010-01-01

    Metabolomics is a fast developing field of comprehensive untargeted chemical analyses. It has many applications and can in principle be used on any organism without prior knowledge of the metabolome or genome. The amount of functional information that is acquired with metabolomics largely depends on

  1. A Metabolomic Signature of Acute Caloric Restriction.

    Science.gov (United States)

    Collet, Tinh-Hai; Sonoyama, Takuhiro; Henning, Elana; Keogh, Julia M; Ingram, Brian; Kelway, Sarah; Guo, Lining; Farooqi, I Sadaf

    2017-12-01

    The experimental paradigm of acute caloric restriction (CR) followed by refeeding (RF) can be used to study the homeostatic mechanisms that regulate energy homeostasis, which are relevant to understanding the adaptive response to weight loss. Metabolomics, the measurement of hundreds of small molecule metabolites, their precursors, derivatives, and degradation products, has emerged as a useful tool for the study of physiology and disease and was used here to study the metabolic response to acute CR. We used four ultra high-performance liquid chromatography-tandem mass spectrometry methods to characterize changes in carbohydrates, lipids, amino acids, and steroids in eight normal weight men at baseline, after 48 hours of CR (10% of energy requirements) and after 48 hours of ad libitum RF in a tightly controlled environment. We identified a distinct metabolomic signature associated with acute CR characterized by the expected switch from carbohydrate to fat utilization with increased lipolysis and β-fatty acid oxidation. We found an increase in ω-fatty acid oxidation and levels of endocannabinoids, which are known to promote food intake. These changes were reversed with RF. Several plasmalogen phosphatidylethanolamines (endogenous antioxidants) significantly decreased with CR (all P ≤ 0.0007). Additionally, acute CR was associated with an increase in the branched chain amino acids (all P ≤ 1.4 × 10-7) and dehydroepiandrosterone sulfate (P = 0.0006). We identified a distinct metabolomic signature associated with acute CR. Further studies are needed to characterize the mechanisms that mediate these changes and their potential contribution to the adaptive response to dietary restriction. Copyright © 2017 Endocrine Society

  2. Metabolomics Approach to Investigate Estrogen Receptor-Dependent and Independent Effects of o,p'-DDT in the Uterus and Brain of Immature Mice.

    Science.gov (United States)

    Wang, Dezhen; Zhu, Wentao; Wang, Yao; Yan, Jin; Teng, Miaomiao; Miao, Jiyan; Zhou, Zhiqiang

    2017-05-10

    Previous studies have demonstrated the endocrine disruption of o,p'-DDT. In this study, we used a 1 H NMR based metabolomics approach to investigate the estrogenic effects of o,p'-DDT (300 mg/kg) on the uterus and brain after 3 days of oral gavage administration, and ethynylestradiol (EE, 100 μg/kg) was used as a positive control. A supervised statistical analysis (PLS-DA) indicated that o,p'-DDT exerted both estrogenic receptor-(ER)-dependent and independent effects on the uterus but mainly ER-independent effects on the brain at metabolome levels, which was verified by coexposing with the antiestrogenic ICI 182,780. Four changed metabolites-glycine, choline, fumarate, and phenylalanine-were identified as ER-independent alterations in the uterus, while more metabolites, including γ-aminobutyrate, N-acetyl aspartate, and some amino acids, were disturbed based on the ER-independent mechanism in the brain. Together with biological end points, metabolomics is a promising approach to study potential estrogenic chemicals.

  3. ¹H-NMR and MS based metabolomics study of the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet.

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    Li, Ze-Yun; Ding, Li-Li; Li, Jin-Mei; Xu, Bao-Li; Yang, Li; Bi, Kai-Shun; Wang, Zheng-Tao

    2015-01-01

    Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD) feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg) or lovastatin (30 mg/kg, positive control) once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both). It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.

  4. ¹H-NMR and MS based metabolomics study of the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet.

    Directory of Open Access Journals (Sweden)

    Ze-Yun Li

    Full Text Available Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg or lovastatin (30 mg/kg, positive control once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both. It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.

  5. Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics.

    Science.gov (United States)

    Sridharan, Gautham Vivek; Bruinsma, Bote; Bale, Shyam Sundhar; Swaminathan, Anandh; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

    2017-11-13

    Large-scale -omics data are now ubiquitously utilized to capture and interpret global responses to perturbations in biological systems, such as the impact of disease states on cells, tissues, and whole organs. Metabolomics data, in particular, are difficult to interpret for providing physiological insight because predefined biochemical pathways used for analysis are inherently biased and fail to capture more complex network interactions that span multiple canonical pathways. In this study, we introduce a nov-el approach coined Metabolomic Modularity Analysis (MMA) as a graph-based algorithm to systematically identify metabolic modules of reactions enriched with metabolites flagged to be statistically significant. A defining feature of the algorithm is its ability to determine modularity that highlights interactions between reactions mediated by the production and consumption of cofactors and other hub metabolites. As a case study, we evaluated the metabolic dynamics of discarded human livers using time-course metabolomics data and MMA to identify modules that explain the observed physiological changes leading to liver recovery during subnormothermic machine perfusion (SNMP). MMA was performed on a large scale liver-specific human metabolic network that was weighted based on metabolomics data and identified cofactor-mediated modules that would not have been discovered by traditional metabolic pathway analyses.

  6. Medicinal Plants: A Public Resource for Metabolomics and Hypothesis Development

    Directory of Open Access Journals (Sweden)

    Eve Syrkin Wurtele

    2012-11-01

    Full Text Available Specialized compounds from photosynthetic organisms serve as rich resources for drug development. From aspirin to atropine, plant-derived natural products have had a profound impact on human health. Technological advances provide new opportunities to access these natural products in a metabolic context. Here, we describe a database and platform for storing, visualizing and statistically analyzing metabolomics data from fourteen medicinal plant species. The metabolomes and associated transcriptomes (RNAseq for each plant species, gathered from up to twenty tissue/organ samples that have experienced varied growth conditions and developmental histories, were analyzed in parallel. Three case studies illustrate different ways that the data can be integrally used to generate testable hypotheses concerning the biochemistry, phylogeny and natural product diversity of medicinal plants. Deep metabolomics analysis of Camptotheca acuminata exemplifies how such data can be used to inform metabolic understanding of natural product chemical diversity and begin to formulate hypotheses about their biogenesis. Metabolomics data from Prunella vulgaris, a species that contains a wide range of antioxidant, antiviral, tumoricidal and anti-inflammatory constituents, provide a case study of obtaining biosystematic and developmental fingerprint information from metabolite accumulation data in a little studied species. Digitalis purpurea, well known as a source of cardiac glycosides, is used to illustrate how integrating metabolomics and transcriptomics data can lead to identification of candidate genes encoding biosynthetic enzymes in the cardiac glycoside pathway. Medicinal Plant Metabolomics Resource (MPM [1] provides a framework for generating experimentally testable hypotheses about the metabolic networks that lead to the generation of specialized compounds, identifying genes that control their biosynthesis and establishing a basis for modeling metabolism in less

  7. Medicinal plants: a public resource for metabolomics and hypothesis development.

    Science.gov (United States)

    Wurtele, Eve Syrkin; Chappell, Joe; Jones, A Daniel; Celiz, Mary Dawn; Ransom, Nick; Hur, Manhoi; Rizshsky, Ludmila; Crispin, Matthew; Dixon, Philip; Liu, Jia; P Widrlechner, Mark; Nikolau, Basil J

    2012-11-21

    Specialized compounds from photosynthetic organisms serve as rich resources for drug development. From aspirin to atropine, plant-derived natural products have had a profound impact on human health. Technological advances provide new opportunities to access these natural products in a metabolic context. Here, we describe a database and platform for storing, visualizing and statistically analyzing metabolomics data from fourteen medicinal plant species. The metabolomes and associated transcriptomes (RNAseq) for each plant species, gathered from up to twenty tissue/organ samples that have experienced varied growth conditions and developmental histories, were analyzed in parallel. Three case studies illustrate different ways that the data can be integrally used to generate testable hypotheses concerning the biochemistry, phylogeny and natural product diversity of medicinal plants. Deep metabolomics analysis of Camptotheca acuminata exemplifies how such data can be used to inform metabolic understanding of natural product chemical diversity and begin to formulate hypotheses about their biogenesis. Metabolomics data from Prunella vulgaris, a species that contains a wide range of antioxidant, antiviral, tumoricidal and anti-inflammatory constituents, provide a case study of obtaining biosystematic and developmental fingerprint information from metabolite accumulation data in a little studied species. Digitalis purpurea, well known as a source of cardiac glycosides, is used to illustrate how integrating metabolomics and transcriptomics data can lead to identification of candidate genes encoding biosynthetic enzymes in the cardiac glycoside pathway. Medicinal Plant Metabolomics Resource (MPM) [1] provides a framework for generating experimentally testable hypotheses about the metabolic networks that lead to the generation of specialized compounds, identifying genes that control their biosynthesis and establishing a basis for modeling metabolism in less studied species. The

  8. Profiling the metabolome changes caused by cranberry procyanidins in plasma of female rats using (1) H NMR and UHPLC-Q-Orbitrap-HRMS global metabolomics approaches.

    Science.gov (United States)

    Liu, Haiyan; Garrett, Timothy J; Tayyari, Fariba; Gu, Liwei

    2015-11-01

    The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using (1) H NMR and UHPLC-Q-Orbitrap-HRMS metabolomics approaches, and to identify the contributing metabolites. Twenty-four female Sprague-Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for three times using a 250 mg extracts/kg body weight dose. Plasma was collected 6 h after the last gavage and analyzed using (1) H NMR and UHPLC-Q-Orbitrap-HRMS. No metabolome difference was observed using (1) H NMR metabolomics approach. However, LC-HRMS metabolomics data show that metabolome in the plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p-hydroxybenzoic acid, phenol, phenol-sulphate, catechol sulphate, 3, 4-dihydroxyphenylvaleric acid, and 4'-O-methyl-(-)-epicatechin-3'-O-beta-glucuronide in rat plasma. Furthermore, the plasma level of O-methyl-(-)-epicatechin-O-glucuronide, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(hydroxyphenyl)-ϒ-valerolactone-O-sulphate, 4-hydroxydiphenylamine, and peonidin-3-O-hexose were higher in female rats administered with PPAP. The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC-Q-Orbitrap-HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Profiling the Metabolome Changes Caused by Cranberry Procyanidins in Plasma of Female Rats using 1H NMR and UHPLC-Q-Orbitrap-HRMS Global Metabolomics Approaches

    Science.gov (United States)

    Liu, Haiyan; Garrett, Timothy J.; Tayyari, Fariba; Gu, Liwei

    2015-01-01

    Scope The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using 1H NMR and UHPLC-Q-Orbitrap-HRMS metabolomics approaches, and to identify the contributing metabolites. Methods and results Twenty four female Sprague-Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for 3 times using a 250 mg extracts/kg body weight dose. Plasma were collected six hours after the last gavage and analyzed using 1H NMR and UHPLC-Q-Orbitrap-HRMS. No metabolome difference was observed using 1H NMR metabolomics approach. However, LC-HRMS metabolomics data show that metabolome in plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p-hydroxybenzoic acid, phenol, phenol-sulfate, catechol sulphate, 3, 4-dihydroxyphenylvaleric acid, and 4′-O-methyl-(−)-epicatechin-3′-O-beta-glucuronide in rat plasma. Furthermore, the plasma level of O-methyl-(−)-epicatechin-O-glucuronide, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(hydroxyphenyl)-γ-valerolactone-O-sulphate, 4-hydroxydiphenylamine, and peonidin-3-O-hexose were higher in female rats administered with PPAP. Conclusion The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC-Q-Orbitrap-HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers. PMID:26264887

  10. A metabolomic analysis of two intravenous lipid emulsions in a murine model.

    Directory of Open Access Journals (Sweden)

    Brian T Kalish

    Full Text Available Parenteral nutrition (PN, including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO has been associated with the development of liver disease, while the administration of intravenous fish oil (FO has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease.We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD, PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany, PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL, or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling.The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors.Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.

  11. Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine.

    Science.gov (United States)

    Su, Qiao; Guan, Tianbing; Lv, Haitao

    2016-04-14

    Uropathogenic Escherichia coli (UPEC) growth in women's bladders during urinary tract infection (UTI) incurs substantial chemical exchange, termed the "interactive metabolome", which primarily accounts for the metabolic costs (utilized metabolome) and metabolic donations (excreted metabolome) between UPEC and human urine. Here, we attempted to identify the individualized interactive metabolome between UPEC and human urine. We were able to distinguish UPEC from non-UPEC by employing a combination of metabolomics and genetics. Our results revealed that the interactive metabolome between UPEC and human urine was markedly different from that between non-UPEC and human urine, and that UPEC triggered much stronger perturbations in the interactive metabolome in human urine. Furthermore, siderophore biosynthesis coordinately modulated the individualized interactive metabolome, which we found to be a critical component of UPEC virulence. The individualized virulence-associated interactive metabolome contained 31 different metabolites and 17 central metabolic pathways that were annotated to host these different metabolites, including energetic metabolism, amino acid metabolism, and gut microbe metabolism. Changes in the activities of these pathways mechanistically pinpointed the virulent capability of siderophore biosynthesis. Together, our findings provide novel insights into UPEC virulence, and we propose that siderophores are potential targets for further discovery of drugs to treat UPEC-induced UTI.

  12. Expression profiling of long non-coding RNA identifies linc-RoR as a prognostic biomarker in oral cancer.

    Science.gov (United States)

    Arunkumar, Ganesan; Deva Magendhra Rao, Arunagiri Kuha; Manikandan, Mayakannan; Arun, Kanagaraj; Vinothkumar, Vilvanathan; Revathidevi, Sundaramoorthy; Rajkumar, Kottayasamy Seenivasagam; Rajaraman, Ramamurthy; Munirajan, Arasambattu Kannan

    2017-04-01

    Oral squamous cell carcinoma is the most aggressive cancer that is associated with high recurrence, metastasis, and poor treatment outcome. Dysregulation of long non-coding RNAs has been shown to promote tumor growth and metastasis in several cancers. In this study, we investigated the expression of 11 selected long non-coding RNAs that are associated with cell proliferation, metastasis, and tumor suppression in oral squamous cell carcinomas and normal tissues by quantitative real-time polymerase chain reaction. Out of the 11 long non-coding RNAs profiled, 9 were significantly overexpressed in tumors with tobacco chewing history. Moreover, the long non-coding RNA profile was similar to the head and neck cancer datasets of The Cancer Genome Atlas database. Linc-RoR, a regulator of reprogramming, implicated in tumorigenesis was found to be overexpressed in undifferentiated tumors and showed strong association with tumor recurrence and poor therapeutic response. In oral squamous cell carcinomas, for the first time, we observed linc-RoR overexpression, downregulation of miR-145-5p, and overexpression of c-Myc, Klf4, Oct4, and Sox2, suggesting the existence of linc-RoR-mediated competing endogenous RNA network in undifferentiated tumors. Taken together, this study demonstrated the association of linc-RoR overexpression in undifferentiated oral tumors and its prognostic value to predict the therapeutic response.

  13. Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination.

    Science.gov (United States)

    Queck, Katherine E; Chapman, Angela; Herzog, Leslie J; Shell-Martin, Tamara; Burgess-Cassler, Anthony; McClure, George David

    2018-03-20

    Periodontal disease in dogs is highly prevalent but can only be accurately diagnosed by performing an anesthetized oral examination with periodontal probing and dental radiography. In this study, 114 dogs had a visual awake examination of the oral cavity and were administered an oral-fluid thiol-detection test prior to undergoing a a full-mouth anesthetized oral examination and digital dental radiographs. The results show the visual awake examination underestimated the presence and severity of active periodontal disease. The thiol-detection test was superior to the visual awake examination at detecting the presence and severity of active periodontal disease and was an indicator of progression toward alveolar bone loss. The thiol-detection test detected active periodontal disease at early stages of development, before any visual cues were present, indicating the need for intervention to prevent periodontal bone loss. Early detection is important because without intervention, dogs with gingivitis (active periodontal disease) progress to irreversible periodontal bone loss (stage 2+). As suggested in the current AAHA guidelines, a thiol-detection test administered in conjunction with the visual awake examination during routine wellness examinations facilitates veterinarian-client communication and mitigates under-diagnosis of periodontal disease and underutilization of dental services. The thiol-detection test can be used to monitor the periodontal health status of the conscious patient during follow-up examinations based on disease severity.

  14. High Resolution Separations and Improved Ion Production and Transmission in Metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Metz, Thomas O.; Page, Jason S.; Baker, Erin Shammel; Tang, Keqi; Ding, Jie; Shen, Yufeng; Smith, Richard D.

    2008-03-31

    The goal of metabolomics experiments is the detection and quantitation of as many sample components as reasonably possible in order to identify “features” that can be used to characterize the samples under study. When utilizing electrospray ionization to produce ions for analysis by mass spectrometry (MS), it is imperative that metabolome sample constituents be efficiently separated prior to ion production, in order to minimize the phenomenon of ionization suppression. Similarly, optimization of the MS inlet can lead to increased measurement sensitivity. This review will focus on the role of high resolution liquid chromatography (LC) separations in conjunction with improved ion production and transmission for LC-MS-based metabolomics.

  15. Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice.

    Science.gov (United States)

    Sun, Jing-Hui; Liu, Xu; Cong, Li-Xin; Li, He; Zhang, Cheng-Yi; Chen, Jian-Guang; Wang, Chun-Mei

    2017-08-01

    Schisandra, a globally distributed plant, has been widely applied for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China. In the present work, a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was conducted to investigate the intervention effect of Schisandra chinensis lignans (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for 4 weeks. Serum biochemistry assay of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) was conducted to confirm the treatment of SCL on lipid regulation. Metabolomics analysis on serum samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of liver lipid metabolism, sterol regulatory element-binding proteins (SREBPs) and its related gene expressions were measured by quantitative real-time polymerase chain reaction (RT-PCR) for investigating the underlying mechanism. Oral administration of SCL significantly decreased the serum levels of TC, TG and LDL-c and increased the serum level of HDL-c in the hyperlipidemia mice, and no effect of SCL on blood lipid levels was observed in control mice. Serum samples were scattered in the PCA scores plots in response to the control, HFD and SCL group. Totally, thirteen biomarkers were identified and nine of them were recovered to the normal levels after SCL treatment. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, the anti-hyperlipidemia mechanisms of SCL may be involved in the following metabolic pathways: tricarboxylic acid (TCA) cycle, synthesis of ketone body and cholesterol

  16. Metabolomic application in toxicity evaluation and toxicological biomarker identification of natural product.

    Science.gov (United States)

    Chen, Dan-Qian; Chen, Hua; Chen, Lin; Tang, Dan-Dan; Miao, Hua; Zhao, Ying-Yong

    2016-05-25

    Natural product plays a vital role in disease prevention and treatment since the appearance of civilization, but the toxicity severely hinders its wide use. In order to avoid toxic effect as far as possible and use natural product safely, more comprehensive understandings of toxicity are urgently required. Since the metabolome represents the physiological or pathological status of organisms, metabolomics-based toxicology is of significance to observe potential injury before toxins have caused physiological or pathological damages. Metabolomics-based toxicology can evaluate toxicity and identify toxicological biomarker of natural product, which is helpful to guide clinical medication and reduce adverse drug reactions. In the past decades, dozens of metabolomic researches have been implemented on toxicity evaluation, toxicological biomarker identification and potential mechanism exploration of nephrotoxicity, hepatotoxicity, cardiotoxicity and central nervous system toxicity induced by pure compounds, extracts and compound prescriptions. In this paper, metabolomic technology, sample preparation, data process and analysis, and metabolomics-based toxicological research of natural product are reviewed, and finally, the potential problems and further perspectives in toxicological metabolomic investigations of natural product are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Metabolomics and detection of colorectal cancer in humans: a systematic review.

    Science.gov (United States)

    Wang, Haili; Tso, Victor K; Slupsky, Carolyn M; Fedorak, Richard N

    2010-09-01

    Metabolomics represents one of the new omics sciences and capitalizes on the unique presence and concentration of small molecules in tissues and body fluids to construct a 'fingerprint' that can be unique to the individual and, within that individual, unique to environmental influences, including health and disease states. As such, metabolomics has the potential to serve an important role in diagnosis and management of human conditions. Colorectal cancer is a major public health concern. Current population-based screening methods are suboptimal and whether metabolomics could represent a new tool of screening is under investigation. The purpose of this systematic review is to summarize existing literature on metabolomics and colorectal cancer, in terms of diagnostic accuracies and distinguishing metabolites. Eight studies are included. A total of 12 metabolites (taurine, lactate, choline, inositol, glycine, phosphocholine, proline, phenylalanine, alanine, threonine, valine and leucine) were found to be more prevalent in colorectal cancer and glucose was found to be in higher proportion in control specimens using tissue metabolomics. Serum and urine metabolomics identified several other differential metabolites between controls and colorectal cancer patients. This article highlights the novelty of the field of metabolomics in colorectal oncology.

  18. Application of a Smartphone Metabolomics Platform to the Authentication of Schisandra sinensis.

    Science.gov (United States)

    Kwon, Hyuk Nam; Phan, Hong-Duc; Xu, Wen Jun; Ko, Yoon-Joo; Park, Sunghyouk

    2016-05-01

    Herbal medicines have been used for a long time all around the world. Since the quality of herbal preparations depends on the source of herbal materials, there has been a strong need to develop methods to correctly identify the origin of materials. To develop a smartphone metabolomics platform as a simpler and low-cost alternative for the identification of herbal material source. Schisandra sinensis extracts from Korea and China were prepared. The visible spectra of all samples were measured by a smartphone spectrometer platform. This platform included all the necessary measures built-in for the metabolomics research: data acquisition, processing, chemometric analysis and visualisation of the results. The result of the smartphone metabolomics platform was compared to that of NMR-based metabolomics, suggesting the feasibility of smartphone platform in metabolomics research. The smartphone metabolomics platform gave similar results to the NMR method, showing good separation between Korean and Chinese materials and correct predictability for all test samples. With its accuracy and advantages of affordability, user-friendliness, and portability, the smartphone metabolomics platform could be applied to the authentication of other medicinal plants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Vitamins, metabolomics, and prostate cancer.

    Science.gov (United States)

    Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

    2017-06-01

    How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

  20. Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study

    OpenAIRE

    Keshteli, Ammar Hassanzadeh; van den Brand, Floris F; Madsen, Karen L; Mandal, Rupasri; Valcheva, Rosica; Kroeker, Karen I; Han, Beomsoo; Bell, Rhonda C; Cole, Janis; Hoevers, Thomas; Wishart, David S; Fedorak, Richard N; Dieleman, Levinus A

    2017-01-01

    AIM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis (UC) patients. METHODS In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatograph...

  1. Preliminary metabolomics analysis of placenta in maternal obesity.

    Science.gov (United States)

    Fattuoni, Claudia; Mandò, Chiara; Palmas, Francesco; Anelli, Gaia Maria; Novielli, Chiara; Parejo Laudicina, Estefanìa; Savasi, Valeria Maria; Barberini, Luigi; Dessì, Angelica; Pintus, Roberta; Fanos, Vassilios; Noto, Antonio; Cetin, Irene

    2018-01-01

    Metabolomics identifies phenotypical groups with specific metabolic profiles, being increasingly applied to several pregnancy conditions. This is the first preliminary study analyzing placental metabolomics in normal weight (NW) and obese (OB) pregnancies. Twenty NW (18.5 ≤ BMI< 25 kg/m 2 ) and eighteen OB (BMI≥ 30 kg/m 2 ) pregnancies were studied. Placental biopsies were collected at elective caesarean section. Metabolites extraction method was optimized for hydrophilic and lipophilic phases, then analyzed with GC-MS. Univariate and PLS-DA multivariate analysis were applied. Univariate analysis showed increased uracil levels while multivariate PLS-DA analysis revealed lower levels of LC-PUFA derivatives in the lipophilic phase and several metabolites with significantly different levels in the hydrophilic phase of OB vs NW. Placental metabolome analysis of obese pregnancies showed differences in metabolites involved in antioxidant defenses, nucleotide production, as well as lipid synthesis and energy production, supporting a shift towards higher placental metabolism. OB placentas also showed a specific fatty acids profile suggesting a disruption of LC-PUFA biomagnification. This study can lay the foundation to further metabolomic placental characterization in maternal obesity. Metabolic signatures in obese placentas may reflect changes occurring in the intrauterine metabolic environment, which may affect the development of adult diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. YMDB: the Yeast Metabolome Database

    Science.gov (United States)

    Jewison, Timothy; Knox, Craig; Neveu, Vanessa; Djoumbou, Yannick; Guo, An Chi; Lee, Jacqueline; Liu, Philip; Mandal, Rupasri; Krishnamurthy, Ram; Sinelnikov, Igor; Wilson, Michael; Wishart, David S.

    2012-01-01

    The Yeast Metabolome Database (YMDB, http://www.ymdb.ca) is a richly annotated ‘metabolomic’ database containing detailed information about the metabolome of Saccharomyces cerevisiae. Modeled closely after the Human Metabolome Database, the YMDB contains >2000 metabolites with links to 995 different genes/proteins, including enzymes and transporters. The information in YMDB has been gathered from hundreds of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the YMDB also contains an extensive collection of experimental intracellular and extracellular metabolite concentration data compiled from detailed Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) metabolomic analyses performed in our lab. This is further supplemented with thousands of NMR and MS spectra collected on pure, reference yeast metabolites. Each metabolite entry in the YMDB contains an average of 80 separate data fields including comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, intracellular/extracellular concentrations, growth conditions and substrates, pathway information, enzyme data, gene/protein sequence data, as well as numerous hyperlinks to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided that support text, chemical structure, spectral, molecular weight and gene/protein sequence queries. Because of S. cervesiae's importance as a model organism for biologists and as a biofactory for industry, we believe this kind of database could have considerable appeal not only to metabolomics researchers, but also to yeast biologists, systems biologists, the industrial fermentation industry, as well as the beer, wine and spirit industry. PMID:22064855

  3. Investigation of Liver Injury of Polygonum multiflorum Thunb. in Rats by Metabolomics and Traditional Approaches

    Science.gov (United States)

    Li, Yun-Xia; Gong, Xiao-Hong; Liu, Mei-Chen; Peng, Cheng; Li, Peng; Wang, Yi-Tao

    2017-01-01

    Liver injury induced by Polygonum multiflorum Thunb. (PM) have been reported since 2006, which aroused widespread concern. However, the toxicity mechanism of PM liver injury remained unclear. In this study, the mechanism of liver injury induced by different doses of PM after long-term administration was investigated in rats by metabolomics and traditional approaches. Rats were randomly divided into control group and PM groups. PM groups were oral administered PM of low (10 g/kg), medium (20 g/kg), high (40 g/kg) dose, while control group was administered distilled water. After 28 days of continuous administration, the serum biochemical indexes in the control and three PM groups were measured and the liver histopathology were analyzed. Also, UPLC-Q-TOF-MS with untargeted metabolomics was performed to identify the possible metabolites and pathway of liver injury caused by PM. Compared with the control group, the serum levels of ALT, AST, ALP, TG, and TBA in middle and high dose PM groups were significantly increased. And the serum contents of T-Bil, D-Bil, TC, TP were significantly decreased. However, there was no significant difference between the low dose group of PM and the control group except serum AST, TG, T-Bil, and D-Bil. Nine biomarkers were identified based on biomarkers analysis. And the pathway analysis indicated that fat metabolism, amino acid metabolism and bile acid metabolism were involved in PM liver injury. Based on the biomarker pathway analysis, PM changed the lipid metabolism, amino acid metabolism and bile acid metabolism and excretion in a dose-dependent manner which was related to the mechanism of liver injury. PMID:29163173

  4. Investigation of Liver Injury of Polygonum multiflorum Thunb. in Rats by Metabolomics and Traditional Approaches

    Directory of Open Access Journals (Sweden)

    Yun-Xia Li

    2017-11-01

    Full Text Available Liver injury induced by Polygonum multiflorum Thunb. (PM have been reported since 2006, which aroused widespread concern. However, the toxicity mechanism of PM liver injury remained unclear. In this study, the mechanism of liver injury induced by different doses of PM after long-term administration was investigated in rats by metabolomics and traditional approaches. Rats were randomly divided into control group and PM groups. PM groups were oral administered PM of low (10 g/kg, medium (20 g/kg, high (40 g/kg dose, while control group was administered distilled water. After 28 days of continuous administration, the serum biochemical indexes in the control and three PM groups were measured and the liver histopathology were analyzed. Also, UPLC-Q-TOF-MS with untargeted metabolomics was performed to identify the possible metabolites and pathway of liver injury caused by PM. Compared with the control group, the serum levels of ALT, AST, ALP, TG, and TBA in middle and high dose PM groups were significantly increased. And the serum contents of T-Bil, D-Bil, TC, TP were significantly decreased. However, there was no significant difference between the low dose group of PM and the control group except serum AST, TG, T-Bil, and D-Bil. Nine biomarkers were identified based on biomarkers analysis. And the pathway analysis indicated that fat metabolism, amino acid metabolism and bile acid metabolism were involved in PM liver injury. Based on the biomarker pathway analysis, PM changed the lipid metabolism, amino acid metabolism and bile acid metabolism and excretion in a dose-dependent manner which was related to the mechanism of liver injury.

  5. Software and Database Usage on Metabolomic Studies: Using XCMS on LC-MS Data Analysis

    Directory of Open Access Journals (Sweden)

    Mustafa Celebier

    2014-04-01

    Full Text Available Metabolome is the complete set of small-molecule metabolites to be found in a cell or a single organism. Metabolomics is the scientific study to determine and identify the chemicals in metabolome with advanced analytical techniques. Nowadays, the elucidation of the molecular mechanism of any disease with genome analysis and proteome analysis is not sufficient. Instead of these, a holistic assessment including metabolomic studies provides rational and accurate results. Metabolite levels in an organism are associated with the cellular functions. Thus, determination of the metabolite amounts identifies the phenotype of a cell or tissue related with the genetic and some other variations. Even though, the analysis of metabolites for medical diagnosis and therapy have been performed for a long time, the studies to improve the analysis methods for metabolite profiling are recently increased. The application of metabolomics includes the identification of biomarkers, enzyme-substract interactions, drug-activity studies, metabolic pathway analysis and some other studies related with the system biology. The preprocessing and computing of the data obtained from LC-MS, GC-MS, CE-MS and NMR for metabolite profiling are helpful for preventing from time consuming manual data analysis processes and possible random errors on profiling period. In addition, such preprocesses allow us to identify low amount of metabolites which are not possible to be analyzed by manual processing. Therefore, the usage of software and databases for this purpose could not be ignored. In this study, it is briefly presented the software and database used on metabolomics and it is evaluated the capability of these software on metabolite profiling. Particularly, the performance of one of the most popular software called XCMS on the evaluation of LC-MS results for metabolomics was overviewed. In the near future, metabolomics with software and database support is estimated to be a routine

  6. Metabolomics Application in Maternal-Fetal Medicine

    OpenAIRE

    Fanos, Vassilios; Atzori, Luigi; Makarenko, Karina; Melis, Gian Benedetto; Ferrazzi, Enrico

    2013-01-01

    Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, prete...

  7. Metabolomics-driven nutraceutical evaluation of diverse green tea cultivars.

    Directory of Open Access Journals (Sweden)

    Yoshinori Fujimura

    Full Text Available BACKGROUND: Green tea has various health promotion effects. Although there are numerous tea cultivars, little is known about the differences in their nutraceutical properties. Metabolic profiling techniques can provide information on the relationship between the metabolome and factors such as phenotype or quality. Here, we performed metabolomic analyses to explore the relationship between the metabolome and health-promoting attributes (bioactivity of diverse Japanese green tea cultivars. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the ability of leaf extracts from 43 Japanese green tea cultivars to inhibit thrombin-induced phosphorylation of myosin regulatory light chain (MRLC in human umbilical vein endothelial cells (HUVECs. This thrombin-induced phosphorylation is a potential hallmark of vascular endothelial dysfunction. Among the tested cultivars, Cha Chuukanbohon Nou-6 (Nou-6 and Sunrouge (SR strongly inhibited MRLC phosphorylation. To evaluate the bioactivity of green tea cultivars using a metabolomics approach, the metabolite profiles of all tea extracts were determined by high-performance liquid chromatography-mass spectrometry (LC-MS. Multivariate statistical analyses, principal component analysis (PCA and orthogonal partial least-squares-discriminant analysis (OPLS-DA, revealed differences among green tea cultivars with respect to their ability to inhibit MRLC phosphorylation. In the SR cultivar, polyphenols were associated with its unique metabolic profile and its bioactivity. In addition, using partial least-squares (PLS regression analysis, we succeeded in constructing a reliable bioactivity-prediction model to predict the inhibitory effect of tea cultivars based on their metabolome. This model was based on certain identified metabolites that were associated with bioactivity. When added to an extract from the non-bioactive cultivar Yabukita, several metabolites enriched in SR were able to transform the extract into a bioactive

  8. Metabolomics-Driven Nutraceutical Evaluation of Diverse Green Tea Cultivars

    Science.gov (United States)

    Ida, Megumi; Kosaka, Reia; Miura, Daisuke; Wariishi, Hiroyuki; Maeda-Yamamoto, Mari; Nesumi, Atsushi; Saito, Takeshi; Kanda, Tomomasa; Yamada, Koji; Tachibana, Hirofumi

    2011-01-01

    Background Green tea has various health promotion effects. Although there are numerous tea cultivars, little is known about the differences in their nutraceutical properties. Metabolic profiling techniques can provide information on the relationship between the metabolome and factors such as phenotype or quality. Here, we performed metabolomic analyses to explore the relationship between the metabolome and health-promoting attributes (bioactivity) of diverse Japanese green tea cultivars. Methodology/Principal Findings We investigated the ability of leaf extracts from 43 Japanese green tea cultivars to inhibit thrombin-induced phosphorylation of myosin regulatory light chain (MRLC) in human umbilical vein endothelial cells (HUVECs). This thrombin-induced phosphorylation is a potential hallmark of vascular endothelial dysfunction. Among the tested cultivars, Cha Chuukanbohon Nou-6 (Nou-6) and Sunrouge (SR) strongly inhibited MRLC phosphorylation. To evaluate the bioactivity of green tea cultivars using a metabolomics approach, the metabolite profiles of all tea extracts were determined by high-performance liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses, principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA), revealed differences among green tea cultivars with respect to their ability to inhibit MRLC phosphorylation. In the SR cultivar, polyphenols were associated with its unique metabolic profile and its bioactivity. In addition, using partial least-squares (PLS) regression analysis, we succeeded in constructing a reliable bioactivity-prediction model to predict the inhibitory effect of tea cultivars based on their metabolome. This model was based on certain identified metabolites that were associated with bioactivity. When added to an extract from the non-bioactive cultivar Yabukita, several metabolites enriched in SR were able to transform the extract into a bioactive extract

  9. NMR and pattern recognition methods in metabolomics: From data acquisition to biomarker discovery: A review

    International Nuclear Information System (INIS)

    Smolinska, Agnieszka; Blanchet, Lionel; Buydens, Lutgarde M.C.; Wijmenga, Sybren S.

    2012-01-01

    Highlights: ► Procedures for acquisition of different biofluids by NMR. ► Recent developments in metabolic profiling of different biofluids by NMR are presented. ► The crucial steps involved in data preprocessing and multivariate chemometric analysis are reviewed. ► Emphasis is given on recent findings on Multiple Sclerosis via NMR and pattern recognition methods. - Abstract: Metabolomics is the discipline where endogenous and exogenous metabolites are assessed, identified and quantified in different biological samples. Metabolites are crucial components of biological system and highly informative about its functional state, due to their closeness to functional endpoints and to the organism's phenotypes. Nuclear Magnetic Resonance (NMR) spectroscopy, next to Mass Spectrometry (MS), is one of the main metabolomics analytical platforms. The technological developments in the field of NMR spectroscopy have enabled the identification and quantitative measurement of the many metabolites in a single sample of biofluids in a non-targeted and non-destructive manner. Combination of NMR spectra of biofluids and pattern recognition methods has driven forward the application of metabolomics in the field of biomarker discovery. The importance of metabolomics in diagnostics, e.g. in identifying biomarkers or defining pathological status, has been growing exponentially as evidenced by the number of published papers. In this review, we describe the developments in data acquisition and multivariate analysis of NMR-based metabolomics data, with particular emphasis on the metabolomics of Cerebrospinal Fluid (CSF) and biomarker discovery in Multiple Sclerosis (MScl).

  10. Metabolomics in Toxicology and Preclinical Research

    Science.gov (United States)

    Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

    2013-01-01

    Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

  11. NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

    Science.gov (United States)

    Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

    2016-08-01

    A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Metabolomics techniques for nanotoxicity investigations.

    Science.gov (United States)

    Lv, Mengying; Huang, Wanqiu; Chen, Zhipeng; Jiang, Hulin; Chen, Jiaqing; Tian, Yuan; Zhang, Zunjian; Xu, Fengguo

    2015-01-01

    Nanomaterials are commonly defined as engineered structures with at least one dimension of 100 nm or less. Investigations of their potential toxicological impact on biological systems and the environment have yet to catch up with the rapid development of nanotechnology and extensive production of nanoparticles. High-throughput methods are necessary to assess the potential toxicity of nanoparticles. The omics techniques are well suited to evaluate toxicity in both in vitro and in vivo systems. Besides genomic, transcriptomic and proteomic profiling, metabolomics holds great promises for globally evaluating and understanding the molecular mechanism of nanoparticle-organism interaction. This manuscript presents a general overview of metabolomics techniques, summarizes its early application in nanotoxicology and finally discusses opportunities and challenges faced in nanotoxicology.

  13. Polyphenol metabolomics of twenty Italian red grape varieties

    Directory of Open Access Journals (Sweden)

    Bavaresco Luigi

    2016-01-01

    Full Text Available “Suspect screening analysis”method to study grape metabolomics, was performed. This method is a middle-way “targeted” and “untargeted”approach aiming at identifying the largest number of metabolites in grape samples. A new database of putative grape and wine metabolites (GrapeMetabolomics, which currently contains around 1,100 compounds, was constructed by CREA at Conegliano. By performing high-resolution mass spectrometry analysis of the grape extract in both positive and negative ionization mode, averaging 320-450 putative compounds are identified. Most of them are grape polyphenols, such as anthocyanins, flavonols and stilbene derivatives. By performing PCA and Cluster Analysis the composition in anthocyanins and flavonols of 20 Italian red grape varieties, was studied.

  14. Metabolomics of Clostridial Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Rabinowitz, Joshua D [Princeton Univ., NJ (United States); Aristilde, Ludmilla [Cornell Univ., Ithaca, NY (United States); Amador-Noguez, Daniel [Univ. of Wisconsin, Madison, WI (United States)

    2015-09-08

    Members of the genus Clostridium collectively have the ideal set of the metabolic capabilities for fermentative biofuel production: cellulose degradation, hydrogen production, and solvent excretion. No single organism, however, can effectively convert cellulose into biofuels. Here we developed, using metabolomics and isotope tracers, basic science knowledge of Clostridial metabolism of utility for future efforts to engineer such an organism. In glucose fermentation carried out by the biofuel producer Clostridium acetobutylicum, we observed a remarkably ordered series of metabolite concentration changes as the fermentation progressed from acidogenesis to solventogenesis. In general, high-energy compounds decreased while low-energy species increased during solventogenesis. These changes in metabolite concentrations were accompanied by large changes in intracellular metabolic fluxes, with pyruvate directed towards acetyl-CoA and solvents instead of oxaloacetate and amino acids. Thus, the solventogenic transition involves global remodeling of metabolism to redirect resources from biomass production into solvent production. In contrast to C. acetobutylicum, which is an avid fermenter, C. cellulolyticum metabolizes glucose only slowly. We find that glycolytic intermediate concentrations are radically different from fast fermenting organisms. Associated thermodynamic and isotope tracer analysis revealed that the full glycolytic pathway in C. cellulolyticum is reversible. This arises from changes in cofactor utilization for phosphofructokinase and an alternative pathway from phosphoenolpyruvate to pyruvate. The net effect is to increase the high-energy phosphate bond yield of glycolysis by 150% (from 2 to 5) at the expense of lower net flux. Thus, C. cellulolyticum prioritizes glycolytic energy efficiency over speed. Degradation of cellulose results in other sugars in addition to glucose. Simultaneous feeding of stable isotope-labeled glucose and unlabeled pentose sugars

  15. Metabolomics and ischaemic heart disease.

    Science.gov (United States)

    Rasmiena, Aliki A; Ng, Theodore W; Meikle, Peter J

    2013-03-01

    Ischaemic heart disease accounts for nearly half of the global cardiovascular disease burden. Aetiologies relating to heart disease are complex, but dyslipidaemia, oxidative stress and inflammation are cardinal features. Despite preventative measures and advancements in treatment regimens with lipid-lowering agents, the high prevalence of heart disease and the residual risk of recurrent events continue to be a significant burden to the health sector and to the affected individuals and their families. The development of improved risk models for the early detection and prevention of cardiovascular events in addition to new therapeutic strategies to address this residual risk are required if we are to continue to make inroads into this most prevalent of diseases. Metabolomics and lipidomics are modern disciplines that characterize the metabolite and lipid complement respectively, of a given system. Their application to ischaemic heart disease has demonstrated utilities in population profiling, identification of multivariate biomarkers and in monitoring of therapeutic response, as well as in basic mechanistic studies. Although advances in magnetic resonance and mass spectrometry technologies have given rise to the fields of metabolomics and lipidomics, the plethora of data generated presents challenges requiring specific statistical and bioinformatics applications, together with appropriate study designs. Nonetheless, the predictive and re-classification capacity of individuals with various degrees of risk by the plasma lipidome has recently been demonstrated. In the present review, we summarize evidence derived exclusively by metabolomic and lipidomic studies in the context of ischaemic heart disease. We consider the potential role of plasma lipid profiling in assessing heart disease risk and therapeutic responses, and explore the potential mechanisms. Finally, we highlight where metabolomic studies together with complementary -omic disciplines may make further

  16. MetaboLights: An Open-Access Database Repository for Metabolomics Data.

    Science.gov (United States)

    Kale, Namrata S; Haug, Kenneth; Conesa, Pablo; Jayseelan, Kalaivani; Moreno, Pablo; Rocca-Serra, Philippe; Nainala, Venkata Chandrasekhar; Spicer, Rachel A; Williams, Mark; Li, Xuefei; Salek, Reza M; Griffin, Julian L; Steinbeck, Christoph

    2016-03-24

    MetaboLights is the first general purpose, open-access database repository for cross-platform and cross-species metabolomics research at the European Bioinformatics Institute (EMBL-EBI). Based upon the open-source ISA framework, MetaboLights provides Metabolomics Standard Initiative (MSI) compliant metadata and raw experimental data associated with metabolomics experiments. Users can upload their study datasets into the MetaboLights Repository. These studies are then automatically assigned a stable and unique identifier (e.g., MTBLS1) that can be used for publication reference. The MetaboLights Reference Layer associates metabolites with metabolomics studies in the archive and is extensively annotated with data fields such as structural and chemical information, NMR and MS spectra, target species, metabolic pathways, and reactions. The database is manually curated with no specific release schedules. MetaboLights is also recommended by journals for metabolomics data deposition. This unit provides a guide to using MetaboLights, downloading experimental data, and depositing metabolomics datasets using user-friendly submission tools. Copyright © 2016 John Wiley & Sons, Inc.

  17. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    Science.gov (United States)

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

  18. [Development of a pharmacological curriculum for general practice: Identifying and prescribing orally administered pharmacological substances with relevance for general practice].

    Science.gov (United States)

    Straßner, Cornelia; Kaufmann-Kolle, Petra; Flum, Elisabeth; Schwill, Simon; Brandt, Bettina; Steinhäuser, Jost

    2017-05-01

    General practitioners (GPs) are among the specialists who prescribe the highest number of medication. Therefore the improvement of pharmacological competencies is an important part of the GP specialist training. The self-concept of general practice stating that GPs are the first contact persons for all health problems makes it challenging to define and acquire competencies for specialist training. While the "Competence-based Curriculum" developed by the German College of General Practitioners and Family Physicians defines diagnoses, reasons for counselling and competencies which are essential for general practice, a similar orientation guide is lacking for the pharmacological field. The aim of this study is to define and characterize pharmacological substances which every GP should know so well that he or she is able to conduct counselling and monitoring. We analysed private and public health insurance prescriptions of all general practices participating in the CONTENT project in the period from 2009 to 2014. The analysis was limited to substances with oral application which were prescribed at least once by at least 25 % (n = 11) of the practices. While the 100 most frequent prescriptions were included due to their frequency, less frequently prescribed substances were assessed concerning their relevance for general practice in a rating procedure. The substances included were classified by diagnoses and reasons for counselling. We analysed 1,912,896 prescriptions from 44 practices and 112,535 patients on the basis of the Anatomical Therapeutic Chemical (ATC) classification system. After applying the inclusion criteria, 453 substances were left, 302 of which were considered relevant for general practice and could be assigned to 45 diagnoses / reasons for counselling. The result of this study could be considered a working draft for a pharmacological curriculum for general practice, which may complement the "Competence-based Curriculum" in the medium term. Copyright

  19. The future of metabolomics in ELIXIR.

    Science.gov (United States)

    van Rijswijk, Merlijn; Beirnaert, Charlie; Caron, Christophe; Cascante, Marta; Dominguez, Victoria; Dunn, Warwick B; Ebbels, Timothy M D; Giacomoni, Franck; Gonzalez-Beltran, Alejandra; Hankemeier, Thomas; Haug, Kenneth; Izquierdo-Garcia, Jose L; Jimenez, Rafael C; Jourdan, Fabien; Kale, Namrata; Klapa, Maria I; Kohlbacher, Oliver; Koort, Kairi; Kultima, Kim; Le Corguillé, Gildas; Moreno, Pablo; Moschonas, Nicholas K; Neumann, Steffen; O'Donovan, Claire; Reczko, Martin; Rocca-Serra, Philippe; Rosato, Antonio; Salek, Reza M; Sansone, Susanna-Assunta; Satagopam, Venkata; Schober, Daniel; Shimmo, Ruth; Spicer, Rachel A; Spjuth, Ola; Thévenot, Etienne A; Viant, Mark R; Weber, Ralf J M; Willighagen, Egon L; Zanetti, Gianluigi; Steinbeck, Christoph

    2017-01-01

    Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the "Future of metabolomics in ELIXIR" was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases.

  20. Identifying the Dimensionality of Oral Language Skills of Children with Typical Development in Preschool through Fifth Grade

    Science.gov (United States)

    Lonigan, Christopher J.; Milburn, Trelani F.

    2017-01-01

    Purpose: Language is a multidimensional construct from prior to the beginning of formal schooling to near the end of elementary school. The primary goals of this study were to identify the dimensionality of language and to determine whether this dimensionality was consistent in children with typical language development from preschool through 5th…

  1. Symbiosis of chemometrics and metabolomics: past, present, and future

    NARCIS (Netherlands)

    van der Greef, J.; Smilde, A. K.

    2005-01-01

    Metabolomics is a growing area in the field of systems biology. Metabolomics has already a long history and also the connection of metabolomics with chemometrics goes back some time. This review discusses the symbiosis of metabolomics and chemometrics with emphasis on the medical domain, puts the

  2. A Metabolomic Perspective on Coeliac Disease

    Science.gov (United States)

    Calabrò, Antonio

    2014-01-01

    Metabolomics is an “omic” science that is now emerging with the purpose of elaborating a comprehensive analysis of the metabolome, which is the complete set of metabolites (i.e., small molecules intermediates) in an organism, tissue, cell, or biofluid. In the past decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. A metabolomics investigation of coeliac disease (CD) revealed that a metabolic fingerprint for CD can be defined, which accounts for three different but complementary components: malabsorption, energy metabolism, and alterations in gut microflora and/or intestinal permeability. In this review, we will discuss the major advancements in metabolomics of CD, in particular with respect to the role of gut microbiome and energy metabolism. PMID:24665364

  3. Metabolomics and bioactive substances in plants

    DEFF Research Database (Denmark)

    Khakimov, Bekzod

    Metabolomic analysis of plants broadens understanding of how plants may benefit humans, animals and the environment, provide sustainable food and energy, and improve current agricultural, pharmacological and medicinal practices in order to bring about healthier and longer life. The quality...... and amount of the extractible biological information is largely determined by data acquisition, data processing and analysis methodologies of the plant metabolomics studies. This PhD study focused mainly on the development and implementation of new metabolomics methodologies for improved data acquisition...... and data processing. The study mainly concerned the three most commonly applied analytical techniques in plant metabolomics, GC-MS, LC-MS and NMR. In addition, advanced chemometrics methods e.g. PARAFAC2 and ASCA have been extensively used for development of complex metabolomics data processing...

  4. Identification of drug targets by chemogenomic and metabolomic profiling in yeast

    KAUST Repository

    Wu, Manhong

    2012-12-01

    OBJECTIVE: To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify drug targets. As measurement of drug-induced changes in cellular metabolites can yield considerable information about the effects of a drug, we investigated whether combining chemogenomic and metabolomic profiling in yeast could improve the characterization of drug targets. BASIC METHODS: We used chemogenomic and metabolomic profiling in yeast to characterize the target for five drugs acting on two biologically important pathways. A novel computational method that uses a curated metabolic network was also developed, and it was used to identify the genes that are likely to be responsible for the metabolomic differences found. RESULTS AND CONCLUSION: The combination of metabolomic and chemogenomic profiling, along with data analyses carried out using a novel computational method, could robustly identify the enzymes targeted by five drugs. Moreover, this novel computational method has the potential to identify genes that are causative of metabolomic differences or drug targets. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  5. Metabolome Consistency: Additional Parazoanthines from the Mediterranean Zoanthid Parazoanthus Axinellae

    Directory of Open Access Journals (Sweden)

    Coralie Audoin

    2014-05-01

    Full Text Available Ultra-high pressure liquid chromatography coupled to high resolution mass spectrometry (UHPLC-MS/MS analysis of the organic extract obtained from the Mediterranean zoanthid Parazoanthus axinellae yielded to the identification of five new parazoanthines F-J. The structures were fully determined by comparison of fragmentation patterns with those of previously isolated parazoathines and MS/MS spectra simulation of in silico predicted compounds according to the metabolome consistency. The absolute configuration of the new compounds has been assigned using on-line electronic circular dichroism (UHPLC-ECD. We thus demonstrated the potential of highly sensitive hyphenated techniques to characterize the structures of a whole family of natural products within the metabolome of a marine species. Minor compounds can be characterized using these techniques thus avoiding long isolation processes that may alter the structure of the natural products. These results are also of interest to identify putative bioactive compounds present at low concentration in a complex mixture.

  6. Metabolome consistency: additional parazoanthines from the mediterranean zoanthid parazoanthus axinellae.

    Science.gov (United States)

    Audoin, Coralie; Cocandeau, Vincent; Thomas, Olivier P; Bruschini, Adrien; Holderith, Serge; Genta-Jouve, Grégory

    2014-05-30

    Ultra-high pressure liquid chromatography coupled to high resolution mass spectrometry (UHPLC-MS/MS) analysis of the organic extract obtained from the Mediterranean zoanthid Parazoanthus axinellae yielded to the identification of five new parazoanthines F-J. The structures were fully determined by comparison of fragmentation patterns with those of previously isolated parazoathines and MS/MS spectra simulation of in silico predicted compounds according to the metabolome consistency. The absolute configuration of the new compounds has been assigned using on-line electronic circular dichroism (UHPLC-ECD). We thus demonstrated the potential of highly sensitive hyphenated techniques to characterize the structures of a whole family of natural products within the metabolome of a marine species. Minor compounds can be characterized using these techniques thus avoiding long isolation processes that may alter the structure of the natural products. These results are also of interest to identify putative bioactive compounds present at low concentration in a complex mixture.

  7. Metabolomics Insights Into Pathophysiological Mechanisms of Interstitial Cystitis

    Science.gov (United States)

    Fiehn, Oliver

    2014-01-01

    Interstitial cystitis (IC), also known as painful bladder syndrome or bladder pain syndrome, is a chronic lower urinary tract syndrome characterized by pelvic pain, urinary urgency, and increased urinary frequency in the absence of bacterial infection or identifiable clinicopathology. IC can lead to long-term adverse effects on the patient's quality of life. Therefore, early diagnosis and better understanding of the mechanisms underlying IC are needed. Metabolomic studies of biofluids have become a powerful method for assessing disease mechanisms and biomarker discovery, which potentially address these important clinical needs. However, limited intensive metabolic profiles have been elucidated in IC. The article is a short review on metabolomic analyses that provide a unique fingerprint of IC with a focus on its use in determining a potential diagnostic biomarker associated with symptoms, a response predictor of therapy, and a prognostic marker. PMID:25279237

  8. Human gut microbes impact host serum metabolome and insulin sensitivity.

    Science.gov (United States)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn; Hyotylainen, Tuulia; Nielsen, Trine; Jensen, Benjamin A H; Forslund, Kristoffer; Hildebrand, Falk; Prifti, Edi; Falony, Gwen; Le Chatelier, Emmanuelle; Levenez, Florence; Doré, Joel; Mattila, Ismo; Plichta, Damian R; Pöhö, Päivi; Hellgren, Lars I; Arumugam, Manimozhiyan; Sunagawa, Shinichi; Vieira-Silva, Sara; Jørgensen, Torben; Holm, Jacob Bak; Trošt, Kajetan; Kristiansen, Karsten; Brix, Susanne; Raes, Jeroen; Wang, Jun; Hansen, Torben; Bork, Peer; Brunak, Søren; Oresic, Matej; Ehrlich, S Dusko; Pedersen, Oluf

    2016-07-21

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.

  9. Analyses of tropistic responses using metabolomics.

    Science.gov (United States)

    Millar, Katherine D L; Kiss, John Z

    2013-01-01

    Characterization of phototropism and gravitropism has been through gene expression studies, assessment of curvature response, and protein expression experiments. To our knowledge, the current study is the first to determine how the metabolome, the complete set of small-molecule metabolites within a plant, is impacted during these tropisms. We have determined the metabolic profile of plants during gravitropism and phototropism. Seedlings of Arabidopsis thaliana wild type (WT) and phyB mutant were exposed to unidirectional light (red or blue) or reoriented to induce a tropistic response, and small-molecule metabolites were assayed and quantified. A subset of the WT was analyzed using microarray experiments to obtain gene profiling data. Analyses of the metabolomic data using principal component analysis showed a common profile in the WT during the different tropistic curvatures, but phyB mutants produced a distinctive profile for each tropism. Interestingly, the gravity treatment elicited the greatest changes in gene expression of the WT, followed by blue light, then by red light treatments. For all tropisms, we identified genes that were downregulated by a large magnitude in carbohydrate metabolism and secondary metabolism. These included ATCSLA15, CELLULOSE SYNTHASE-LIKE, and ATCHS/SHS/TT4, CHALCONE SYNTHASE. In addition, genes involved in amino acid biosynthesis were strongly upregulated, and these included THA1 (THREONINE ALDOLASE 1) and ASN1 (DARK INDUCIBLE asparagine synthase). We have established the first metabolic profile of tropisms in conjunction with transcriptomic analyses. This approach has been useful in characterizing the similarities and differences in the molecular mechanisms involved with phototropism and gravitropism.

  10. Computational Metabolomics Operations at BioCyc.org

    Directory of Open Access Journals (Sweden)

    Peter D. Karp

    2015-05-01

    Full Text Available BioCyc.org is a genome and metabolic pathway web portal covering 5500 organisms, including Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae and Escherichia coli. These organism-specific databases have undergone variable degrees of curation. The EcoCyc (Escherichia coli Encyclopedia database is the most highly curated; its contents have been derived from 27,000 publications. The MetaCyc (Metabolic Encyclopedia database within BioCyc is a “universal” metabolic database that describes pathways, reactions, enzymes and metabolites from all domains of life. Metabolic pathways provide an organizing framework for analyzing metabolomics data, and the BioCyc website provides computational operations for metabolomics data that include metabolite search and translation of metabolite identifiers across multiple metabolite databases. The site allows researchers to store and manipulate metabolite lists using a facility called SmartTables, which supports metabolite enrichment analysis. That analysis operation identifies metabolite sets that are statistically over-represented for the substrates of specific metabolic pathways. BioCyc also enables visualization of metabolomics data on individual pathway diagrams and on the organism-specific metabolic map diagrams that are available for every BioCyc organism. Most of these operations are available both interactively and as programmatic web services.

  11. NMR metabolomics of thrips (Frankliniella occidentalis) resistance in Senecio hybrids.

    Science.gov (United States)

    Leiss, Kirsten A; Choi, Young H; Abdel-Farid, Ibrahim B; Verpoorte, Robert; Klinkhamer, Peter G L

    2009-02-01

    Western flower thrips (Frankliniella occidentalis) has become a key insect pest of agricultural and horticultural crops worldwide. Little is known about host plant resistance to thrips. In this study, we investigated thrips resistance in F (2) hybrids of Senecio jacobaea and Senecio aquaticus. We identified thrips-resistant hybrids applying three different bioassays. Subsequently, we compared the metabolomic profiles of these hybrids applying nuclear magnetic resonance spectroscopy (NMR). The new developments of NMR facilitate a wide range coverage of the metabolome. This makes NMR especially suitable if there is no a priori knowledge of the compounds related to herbivore resistance and allows a holistic approach analyzing different chemical compounds simultaneously. We show that the metabolomes of thrips-resistant and -susceptible hybrids differed considerably. Thrips-resistant hybrids contained higher amounts of the pyrrolizidine alkaloids (PA), jacobine, and jaconine, especially in younger leaves. Also, a flavanoid, kaempferol glucoside, accumulated in the resistant plants. Both PAs and kaempferol are known for their inhibitory effect on herbivores. In resistant and susceptible F (2) hybrids, young leaves showed less thrips damage than old leaves. Consistent with the optimal plant defense theory, young leaves contained increased levels of primary metabolites such as sucrose, raffinose, and stachyose, but also accumulated jacaranone as a secondary plant defense compound. Our results prove NMR as a promising tool to identify different metabolites involved in herbivore resistance. It constitutes a significant advance in the study of plant-insect relationships, providing key information on the implementation of herbivore resistance breeding strategies in plants.

  12. Proteomics and Metabolomics: two emerging areas for legume improvement

    Directory of Open Access Journals (Sweden)

    Abirami eRamalingam

    2015-12-01

    Full Text Available The crop legumes such as chickpea, common bean, cowpea, peanut, pigeonpea, soybean, etc. are important source of nutrition and contribute to a significant amount of biological nitrogen fixation (>20 million tons of fixed nitrogen in agriculture. However, the production of legumes is constrained due to abiotic and biotic stresses. It is therefore imperative to understand the molecular mechanisms of plant response to different stresses and identify key candidate genes regulating tolerance which can be deployed in breeding programs. The information obtained from transcriptomics has facilitated the identification of candidate genes for the given trait of interest and utilizing them in crop breeding programs to improve stress tolerance. However, the mechanisms of stress tolerance are complex due to the influence of multi-genes and post-transcriptional regulations. Furthermore, stress conditions greatly affect gene expression which in turn causes modifications in the composition of plant proteomes and metabolomes. Therefore, functional genomics involving various proteomics and metabolomics approaches have been obligatory for understanding plant stress tolerance. These approaches have also been found useful to unravel different pathways related to plant and seed development as well as symbiosis. Proteome and metabolome profiling using high-throughput based systems have been extensively applied in the model legume species Medicago truncatula and Lotus japonicus, as well as in the model crop legume, soybean, to examine stress signalling pathways, cellular and developmental processes and nodule symbiosis. Moreover, the availability of protein reference maps as well as proteomics and metabolomics databases greatly support research and understanding of various biological processes in legumes. Protein-protein interaction techniques, particularly the yeast two-hybrid system have been advantageous for studying symbiosis and stress signalling in legumes. In

  13. Identifying the Dimensionality of Oral Language Skills of Children With Typical Development in Preschool Through Fifth Grade.

    Science.gov (United States)

    Lonigan, Christopher J; Milburn, Trelani F

    2017-08-16

    Language is a multidimensional construct from prior to the beginning of formal schooling to near the end of elementary school. The primary goals of this study were to identify the dimensionality of language and to determine whether this dimensionality was consistent in children with typical language development from preschool through 5th grade. In a large sample of 1,895 children, confirmatory factor analysis was conducted with 19-20 measures of language intended to represent 6 factors, including domains of vocabulary and syntax/grammar across modalities of expressive and receptive language, listening comprehension, and vocabulary depth. A 2-factor model with separate, highly correlated vocabulary and syntax factors provided the best fit to the data, and this model of language dimensionality was consistent from preschool through 5th grade. This study found that there are fewer dimensions than are often suggested or represented by the myriad subtests in commonly used standardized tests of language. The identified 2-dimensional (vocabulary and syntax) model of language has significant implications for the conceptualization and measurement of the language skills of children in the age range from preschool to 5th grade, including the study of typical and atypical language development, the study of the developmental and educational influences of language, and classification and intervention in clinical practice. https://doi.org/10.23641/asha.5154220.

  14. Functional Analysis of Metabolomics Data.

    Science.gov (United States)

    Chagoyen, Mónica; López-Ibáñez, Javier; Pazos, Florencio

    2016-01-01

    Metabolomics aims at characterizing the repertory of small chemical compounds in a biological sample. As it becomes more massive and larger sets of compounds are detected, a functional analysis is required to convert these raw lists of compounds into biological knowledge. The most common way of performing such analysis is "annotation enrichment analysis," also used in transcriptomics and proteomics. This approach extracts the annotations overrepresented in the set of chemical compounds arisen in a given experiment. Here, we describe the protocols for performing such analysis as well as for visualizing a set of compounds in different representations of the metabolic networks, in both cases using free accessible web tools.

  15. Elucidation of cellular metabolism via metabolomics and stable-isotope assisted metabolomics.

    Science.gov (United States)

    Hiller, Karsten; Metallo, Christian; Stephanopoulos, Gregory

    2011-07-01

    Metabolomics and metabolic flux analysis (MFA) are powerful tools in the arsenal of methodologies of systems biology. Currently, metabolomics techniques are applied routinely for biomarker determination. However, standard metabolomics techniques only provide static information about absolute or relative metabolite amounts. The application of stable-isotope tracers has opened up a new dimension to metabolomics by providing dynamic information of intracellular fluxes and, by extension, enzyme activities. In the first part of the manuscript we review experimental and computational technologies applicable for metabolomics analyses. In the second part we present current technologies based on the use of stable isotopes and their applications to the analysis of cellular metabolism. Beginning with the determination of mass isotopomer distributions (MIDs), we review technologies for metabolic flux analysis (MFA) and conclude with the presentation of a new methodology for the non-targeted analysis of stable-isotope labeled metabolomics data.

  16. Probabilistic Principal Component Analysis for Metabolomic Data.

    LENUS (Irish Health Repository)

    Nyamundanda, Gift

    2010-11-23

    Abstract Background Data from metabolomic studies are typically complex and high-dimensional. Principal component analysis (PCA) is currently the most widely used statistical technique for analyzing metabolomic data. However, PCA is limited by the fact that it is not based on a statistical model. Results Here, probabilistic principal component analysis (PPCA) which addresses some of the limitations of PCA, is reviewed and extended. A novel extension of PPCA, called probabilistic principal component and covariates analysis (PPCCA), is introduced which provides a flexible approach to jointly model metabolomic data and additional covariate information. The use of a mixture of PPCA models for discovering the number of inherent groups in metabolomic data is demonstrated. The jackknife technique is employed to construct confidence intervals for estimated model parameters throughout. The optimal number of principal components is determined through the use of the Bayesian Information Criterion model selection tool, which is modified to address the high dimensionality of the data. Conclusions The methods presented are illustrated through an application to metabolomic data sets. Jointly modeling metabolomic data and covariates was successfully achieved and has the potential to provide deeper insight to the underlying data structure. Examination of confidence intervals for the model parameters, such as loadings, allows for principled and clear interpretation of the underlying data structure. A software package called MetabolAnalyze, freely available through the R statistical software, has been developed to facilitate implementation of the presented methods in the metabolomics field.

  17. Create, run, share, publish, and reference your LC-MS, FIA-MS, GC-MS, and NMR data analysis workflows with the Workflow4Metabolomics 3.0 Galaxy online infrastructure for metabolomics.

    Science.gov (United States)

    Guitton, Yann; Tremblay-Franco, Marie; Le Corguillé, Gildas; Martin, Jean-François; Pétéra, Mélanie; Roger-Mele, Pierrick; Delabrière, Alexis; Goulitquer, Sophie; Monsoor, Misharl; Duperier, Christophe; Canlet, Cécile; Servien, Rémi; Tardivel, Patrick; Caron, Christophe; Giacomoni, Franck; Thévenot, Etienne A

    2017-12-01

    Metabolomics is a key approach in modern functional genomics and systems biology. Due to the complexity of metabolomics data, the variety of experimental designs, and the multiplicity of bioinformatics tools, providing experimenters with a simple and efficient resource to conduct comprehensive and rigorous analysis of their data is of utmost importance. In 2014, we launched the Workflow4Metabolomics (W4M; http://workflow4metabolomics.org) online infrastructure for metabolomics built on the Galaxy environment, which offers user-friendly features to build and run data analysis workflows including preprocessing, statistical analysis, and annotation steps. Here we present the new W4M 3.0 release, which contains twice as many tools as the first version, and provides two features which are, to our knowledge, unique among online resources. First, data from the four major metabolomics technologies (i.e., LC-MS, FIA-MS, GC-MS, and NMR) can be analyzed on a single platform. By using three studies in human physiology, alga evolution, and animal toxicology, we demonstrate how the 40 available tools can be easily combined to address biological issues. Second, the full analysis (including the workflow, the parameter values, the input data and output results) can be referenced with a permanent digital object identifier (DOI). Publication of data analyses is of major importance for robust and reproducible science. Furthermore, the publicly shared workflows are of high-value for e-learning and training. The Workflow4Metabolomics 3.0 e-infrastructure thus not only offers a unique online environment for analysis of data from the main metabolomics technologies, but it is also the first reference repository for metabolomics workflows. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows.

    Science.gov (United States)

    Imhasly, Sandro; Naegeli, Hanspeter; Baumann, Sven; von Bergen, Martin; Luch, Andreas; Jungnickel, Harald; Potratz, Sarah; Gerspach, Christian

    2014-06-02

    Hepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals. To identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder. This proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome.

  19. The role of metabolomics in neonatal and pediatric laboratory medicine.

    Science.gov (United States)

    Mussap, Michele; Antonucci, Roberto; Noto, Antonio; Fanos, Vassilios

    2013-11-15

    Metabolomics consists of the quantitative analysis of a large number of low molecular mass metabolites involving substrates or products in metabolic pathways existing in all living systems. The analysis of the metabolic profile detectable in a human biological fluid allows to instantly identify changes in the composition of endogenous and exogenous metabolites caused by the interaction between specific physiopathological states, gene expression, and environment. In pediatrics and neonatology, metabolomics offers new encouraging perspectives for the improvement of critically ill patient outcome, for the early recognition of metabolic profiles associated with the development of diseases in the adult life, and for delivery of individualized medicine. In this view, nutrimetabolomics, based on the recognition of specific cluster of metabolites associated with nutrition and pharmacometabolomics, based on the capacity to personalize drug therapy by analyzing metabolic modifications due to therapeutic treatment may open new frontiers in the prevention and in the treatment of pediatric and neonatal diseases. This review summarizes the most relevant results published in the literature on the application of metabolomics in pediatric and neonatal clinical settings. However, there is the urgent need to standardize physiological and preanalytical variables, analytical methods, data processing, and result presentation, before establishing the definitive clinical value of results. © 2013 Elsevier B.V. All rights reserved.

  20. Solid-phase microextraction and the human fecal VOC metabolome.

    Directory of Open Access Journals (Sweden)

    Emma Dixon

    2011-04-01

    Full Text Available The diagnostic potential and health implications of volatile organic compounds (VOCs present in human feces has begun to receive considerable attention. Headspace solid-phase microextraction (SPME has greatly facilitated the isolation and analysis of VOCs from human feces. Pioneering human fecal VOC metabolomic investigations have utilized a single SPME fiber type for analyte extraction and analysis. However, we hypothesized that the multifarious nature of metabolites present in human feces dictates the use of several diverse SPME fiber coatings for more comprehensive metabolomic coverage. We report here an evaluation of eight different commercially available SPME fibers, in combination with both GC-MS and GC-FID, and identify the 50/30 µm CAR-DVB-PDMS, 85 µm CAR-PDMS, 65 µm DVB-PDMS, 7 µm PDMS, and 60 µm PEG SPME fibers as a minimal set of fibers appropriate for human fecal VOC metabolomics, collectively isolating approximately 90% of the total metabolites obtained when using all eight fibers. We also evaluate the effect of extraction duration on metabolite isolation and illustrate that ex vivo enteric microbial fermentation has no effect on metabolite composition during prolonged extractions if the SPME is performed as described herein.

  1. Biomarker discovery in neurological diseases: a metabolomic approach

    Directory of Open Access Journals (Sweden)

    Afaf El-Ansary

    2009-12-01

    Full Text Available Afaf El-Ansary, Nouf Al-Afaleg, Yousra Al-YafaeeBiochemistry Department, Science College, King Saud University, Riyadh, Saudi ArabiaAbstract: Biomarkers are pharmacological and physiological measurements or specific biochemicals in the body that have a particular molecular feature that makes them useful for measuring the progress of disease or the effects of treatment. Due to the complexity of neurological disorders, it is very difficult to have perfect markers. Brain diseases require plenty of markers to reflect the metabolic impairment of different brain cells. The recent introduction of the metabolomic approach helps the study of neurological diseases based on profiling a multitude of biochemical components related to brain metabolism. This review is a trial to elucidate the possibility to use this approach to identify plasma metabolic markers related to neurological disorders. Previous trials using different metabolomic analyses including nuclear magnetic resonance spectroscopy, gas chromatography combined with mass spectrometry, liquid chromatography combined with mass spectrometry, and capillary electrophoresis will be traced.Keywords: metabolic biomarkers, neurological disorders. metabolome, nuclear magnetic resonance, mass spectrometry, chromatography

  2. The Time Is Right to Focus on Model Organism Metabolomes.

    Science.gov (United States)

    Edison, Arthur S; Hall, Robert D; Junot, Christophe; Karp, Peter D; Kurland, Irwin J; Mistrik, Robert; Reed, Laura K; Saito, Kazuki; Salek, Reza M; Steinbeck, Christoph; Sumner, Lloyd W; Viant, Mark R

    2016-02-15

    Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  3. The Time Is Right to Focus on Model Organism Metabolomes

    Directory of Open Access Journals (Sweden)

    Arthur S. Edison

    2016-02-01

    Full Text Available Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  4. Metabolomics as a promising tool for early osteoarthritis diagnosis

    Directory of Open Access Journals (Sweden)

    E.B. de Sousa

    2017-09-01

    Full Text Available Osteoarthritis (OA is the main cause of disability worldwide, due to progressive articular cartilage loss and degeneration. According to recent research, OA is more than just a degenerative disease due to some metabolic components associated to its pathogenesis. However, no biomarker has been identified to detect this disease at early stages or to track its development. Metabolomics is an emerging field and has the potential to detect many metabolites in a single spectrum using high resolution nuclear magnetic resonance (NMR techniques or mass spectrometry (MS. NMR is a reproducible and reliable non-destructive analytical method. On the other hand, MS has a lower detection limit and is more destructive, but it is more sensitive. NMR and MS are useful for biological fluids, such as urine, blood plasma, serum, or synovial fluid, and have been used for metabolic profiling in dogs, mice, sheep, and humans. Thus, many metabolites have been listed as possibly associated to OA pathogenesis. The goal of this review is to provide an overview of the studies in animal models and humans, regarding the use of metabolomics as a tool for early osteoarthritis diagnosis. The concept of osteoarthritis as a metabolic disease and the importance of detecting a biomarker for its early diagnosis are highlighted. Then, some studies in plasma and synovial tissues are shown, and finally the application of metabolomics in the evaluation of synovial fluid is described.

  5. Maternal Plasma Metabolomic Profiles in Spontaneous Preterm Birth: Preliminary Results

    Directory of Open Access Journals (Sweden)

    Barbara Lizewska

    2018-01-01

    Full Text Available Objective. To profile maternal plasma metabolome in spontaneous preterm birth. Method. In this retrospective case-control study, we have examined plasma of patient with preterm birth (between 22 and 36 weeks of pregnancy (n=57, with threatened preterm labor (between 23 and 36 weeks of pregnancy (n=49, and with term delivery (n=25. Plasma samples were analysed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS in positive and negative polarity modes. Results. We found 168 differentially expressed metabolites that were significantly distinct between study groups. We determined 51 metabolites using publicly available databases that could be subdivided into one of the five groups: amino acids, fatty acids, lipids, hormones, and bile acids. PLS-DA models, verified by SVM classification accuracy, differentiated preterm birth and term delivery groups. Conclusions. Maternal plasma metabolites are different between term and preterm parturitions. Part of them may be related with preterm labor, while others may be affected by gestational age or the beginning of labor. Metabolite profile can classify preterm or term delivery groups raising the potential of metabolome as a biomarker to identify high-risk pregnancies. Metabolomic studies are also a tool to detect individual compounds that may be further tested in targeted researches.

  6. Using next generation transcriptome sequencing to predict an ectomycorrhizal metabolome

    Directory of Open Access Journals (Sweden)

    Cseke Leland J

    2011-05-01

    Full Text Available Abstract Background Mycorrhizae, symbiotic interactions between soil fungi and tree roots, are ubiquitous in terrestrial ecosystems. The fungi contribute phosphorous, nitrogen and mobilized nutrients from organic matter in the soil and in return the fungus receives photosynthetically-derived carbohydrates. This union of plant and fungal metabolisms is the mycorrhizal metabolome. Understanding this symbiotic relationship at a molecular level provides important contributions to the understanding of forest ecosystems and global carbon cycling. Results We generated next generation short-read transcriptomic sequencing data from fully-formed ectomycorrhizae between Laccaria bicolor and aspen (Populus tremuloides roots. The transcriptomic data was used to identify statistically significantly expressed gene models using a bootstrap-style approach, and these expressed genes were mapped to specific metabolic pathways. Integration of expressed genes that code for metabolic enzymes and the set of expressed membrane transporters generates a predictive model of the ectomycorrhizal metabolome. The generated model of mycorrhizal metabolome predicts that the specific compounds glycine, glutamate, and allantoin are synthesized by L. bicolor and that these compounds or their metabolites may be used for the benefit of aspen in exchange for the photosynthetically-derived sugars fructose and glucose. Conclusions The analysis illustrates an approach to generate testable biological hypotheses to investigate the complex molecular interactions that drive ectomycorrhizal symbiosis. These models are consistent with experimental environmental data and provide insight into the molecular exchange processes for organisms in this complex ecosystem. The method used here for predicting metabolomic models of mycorrhizal systems from deep RNA sequencing data can be generalized and is broadly applicable to transcriptomic data derived from complex systems.

  7. Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

    Directory of Open Access Journals (Sweden)

    Ruben t'Kindt

    Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

  8. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Neeraja Krishnan

    2015-11-01

    Full Text Available Oral tongue squamous cell carcinomas (OTSCC are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs, indels, regions with loss of heterozygosity (LOH, and copy number variations (CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

  9. Short overview on metabolomic approach and redox changes in psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Gordana Nedic Erjavec

    2018-04-01

    Full Text Available Schizophrenia, depression and posttraumatic stress disorder (PTSD are severe mental disorders and complicated diagnostic entities, due to their phenotypic, biological and genetic heterogeneity, unknown etiology, and poorly understood alterations in biological pathways and biological mechanisms. Disturbed homeostasis between overproduction of oxidant species, overcoming redox regulation and a lack of cellular antioxidant defenses, resulting in free radical-mediated pathology and subsequent neurotoxicity contributes to development of depression, schizophrenia and PTSD, their heterogeneous clinical presentation and resistance to treatment. Metabolomics is a discipline that combines different strategies with the aim to extract, detect, identify and quantify all metabolites that are present in a biological sample and might provide mechanistic insights into the etiology of various psychiatric disorders. Therefore, oxidative stress research combined with metabolomics might offer a novel approach in dissecting psychiatric disorders, since these data-driven but not necessarily hypothesis-driven methods might identify new targets, molecules and pathways responsible for development of schizophrenia, depression or PTSD. Findings from the oxidative research in psychiatry together with metabolomics data might facilitate development of specific and validated prognostic, therapeutic and clinical biomarkers. These methods might reveal bio-signatures of individual patients, leading to individualized treatment approach. In reviewing findings related to oxidative stress and metabolomics in selected psychiatric disorders, we have highlighted how these novel approaches might make a unique contribution to deeper understanding of psychopathological alterations underlying schizophrenia, depression and PTSD. Keywords: Schizophrenia, Depression, Posttraumatic stress disorder, Oxidative stress, Lipid peroxidation, Metabolomics, Biomarkers

  10. (1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors

    OpenAIRE

    Vázquez Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez Martínez, Miguel Ángel; Vinaixa Crevillent, Maria; Chiva Blanch, Gemma; Estruch Riba, Ramon; Correig Blanchar, Xavier; Andrés Lacueva, Ma. Cristina

    2012-01-01

    Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100m...

  11. UHPLC-Q-Orbitrap-HRMS-based global metabolomics reveal metabolome modifications in plasma of young women after cranberry juice consumption.

    Science.gov (United States)

    Liu, Haiyan; Garrett, Timothy J; Su, Zhihua; Khoo, Christina; Gu, Liwei

    2017-07-01

    Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Characterizing Dissolved Organic Matter and Metabolites in an Actively Serpentinizing Ophiolite Using Global Metabolomics Techniques

    Science.gov (United States)

    Seyler, L. M.; Rempfert, K. R.; Kraus, E. A.; Spear, J. R.; Templeton, A. S.; Schrenk, M. O.

    2017-12-01

    Environmental metabolomics is an emerging approach used to study ecosystem properties. Through bioinformatic comparisons to metagenomic data sets, metabolomics can be used to study microbial adaptations and responses to varying environmental conditions. Since the techniques are highly parallel to organic geochemistry approaches, metabolomics can also provide insight into biogeochemical processes. These analyses are a reflection of metabolic potential and intersection with other organisms and environmental components. Here, we used an untargeted metabolomics approach to characterize dissolved organic carbon and aqueous metabolites from groundwater obtained from an actively serpentinizing habitat. Serpentinites are known to support microbial communities that feed off of the products of serpentinization (such as methane and H2 gas), while adapted to harsh environmental conditions such as high pH and low DIC availability. However, the biochemistry of microbial populations that inhabit these environments are understudied and are complicated by overlapping biotic and abiotic processes. The aim of this study was to identify potential sources of carbon in an environment that is depleted of soluble inorganic carbon, and to characterize the flow of metabolites and describe overlapping biogenic and abiogenic processes impacting carbon cycling in serpentinizing rocks. We applied untargeted metabolomics techniques to groundwater taken from a series of wells drilled into the Semail Ophiolite in Oman.. Samples were analyzed via quadrupole time-of-flight liquid chromatography tandem mass spectrometry (QToF-LC/MS/MS). Metabolomes and metagenomic data were imported into Progenesis QI software for statistical analysis and correlation, and metabolic networks constructed using the Genome-Linked Application for Metabolic Maps (GLAMM), a web interface tool. Further multivariate statistical analyses and quality control was performed using EZinfo. Pools of dissolved organic carbon could

  13. Metabolomics study of human urinary metabolome modifications after intake of almond (Prunus dulcis (Mill.) D.A. Webb) skin polyphenols.

    Science.gov (United States)

    Llorach, Rafael; Garrido, Ignacio; Monagas, Maria; Urpi-Sarda, Mireia; Tulipani, Sara; Bartolome, Begona; Andres-Lacueva, Cristina

    2010-11-05

    Almond, as a part of the nut family, is an important source of biological compounds, and specifically, almond skins have been considered an important source of polyphenols, including flavan-3-ols and flavonols. Polyphenol metabolism may produce several classes of metabolites that could often be more biologically active than their dietary precursor and could also become a robust new biomarker of almond polyphenol intake. In order to study urinary metabolome modifications during the 24 h after a single dose of almond skin extract, 24 volunteers (n = 24), who followed a polyphenol-free diet for 48 h before and during the study, ingested a dietary supplement of almond skin phenolic compounds (n = 12) or a placebo (n = 12). Urine samples were collected before ((-2)-0 h) and after (0-2 h, 2-6 h, 6-10 h, and 10-24 h) the intake and were analyzed by liquid chromatography-mass spectrometry (LC-q-TOF) and multivariate statistical analysis (principal component analysis (PCA) and orthogonal projection to latent structures (OPLS)). Putative identification of relevant biomarkers revealed a total of 34 metabolites associated with the single dose of almond extract, including host and, in particular, microbiota metabolites. As far as we know, this is the first time that conjugates of hydroxyphenylvaleric, hydroxyphenylpropionic, and hydroxyphenylacetic acids have been identified in human samples after the consumption of flavan-3-ols through a metabolomic approach. The results showed that this non-targeted approach could provide new intake biomarkers, contributing to the development of the food metabolome as an important part of the human urinary metabolome.

  14. Metabolomics Application in Maternal-Fetal Medicine

    Directory of Open Access Journals (Sweden)

    Vassilios Fanos

    2013-01-01

    Full Text Available Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. The aim of this review is to summarize and comment on original data available in relevant published works in order to emphasize the clinical potential of metabolomics in obstetrics in the immediate future.

  15. Identifying second language speech tasks and ability levels for successful nurse oral interaction with patients in a linguistic minority setting: an instrument development project.

    Science.gov (United States)

    Isaacs, Talia; Laurier, Michel D; Turner, Carolyn E; Segalowitz, Norman

    2011-09-01

    One of the most demanding situations for members of linguistic minorities is a conversation between a health professional and a patient, a situation that frequently arises for linguistic minority groups in North America, Europe, and elsewhere. The present study reports on the construction of an oral interaction scale for nurses serving linguistic minorities in their second language (L2). A mixed methods approach was used to identify and validate a set of speech activities relating to nurse interactions with patients and to derive the L2 ability required to carry out those tasks. The research included an extensive literature review, the development of an initial list of speech tasks, and validation of this list with a nurse focus group. The retained speech tasks were then developed into a questionnaire and administered to 133 Quebec nurses who assessed each speech task for difficulty in an L2 context. Results were submitted to Rasch analysis and calibrated with reference to the Canadian Language Benchmarks, and the constructs underlying the speech tasks were identified through exploratory and confirmatory factor analyses. Results showed that speech tasks dealing with emotional aspects of caregiving and conveying health-specific information were reported as being the most demanding in terms of L2 ability, and the most strongly associated with L2 ability required for nurse-patient interactions. Implications are discussed with respect to the development and use of assessment instruments to facilitate L2 workplace training for health care professionals.

  16. [Metabolomics in research of phytotherapeutics].

    Science.gov (United States)

    Kráfová, Katarina; Jampílek, Josef; Ostrovský, Ivan

    2012-02-01

    Pharmaceutical and food industries are increasingly focused on the great potential of plant secondary metabolites or natural substances which can be used as therapeutics or model compounds for development of new drugs. The paper is devoted to the use of metabolomics, metabolic profiling and metabolic "fingerprint" for the identification of individual active phyto-substances in plant extracts, in profiling of unique groups of plant secondary metabolites that can be used to improve the classification of several species of medicinal plants as well as for a better characterization and quality control of medicinal extracts, tinctures and phytotherapeutic products prepared from these plants. Combined analytical methods and multivariate statistical analysis are used for metabolite identification. Using this approach, medicinal plants are evaluated not only on the basis of a limited number of pharmacologically important metabolites but also based on the fingerprints of minor metabolites and bioactive molecules.

  17. Emerging field of metabolomics: big promise for cancer biomarker identification and drug discovery.

    Science.gov (United States)

    Patel, Seema; Ahmed, Shadab

    2015-03-25

    Most cancers are lethal and metabolic alterations are considered a hallmark of this deadly disease. Genomics and proteomics have contributed vastly to understand cancer biology. Still there are missing links as downstream to them molecular divergence occurs. Metabolomics, the omic science that furnishes a dynamic portrait of metabolic profile is expected to bridge these gaps and boost cancer research. Metabolites being the end products are more stable than mRNAs or proteins. Previous studies have shown the efficacy of metabolomics in identifying biomarkers associated with diagnosis, prognosis and treatment of cancer. Metabolites are highly informative about the functional status of the biological system, owing to their proximity to organismal phenotypes. Scores of publications have reported about high-throughput data generation by cutting-edge analytic platforms (mass spectrometry and nuclear magnetic resonance). Further sophisticated statistical softwares (chemometrics) have enabled meaningful information extraction from the metabolomic data. Metabolomics studies have demonstrated the perturbation in glycolysis, tricarboxylic acid cycle, choline and fatty acid metabolism as traits of cancer cells. This review discusses the latest progress in this field, the future trends and the deficiencies to be surmounted for optimally implementation in oncology. The authors scoured through the most recent, high-impact papers archived in Pubmed, ScienceDirect, Wiley and Springer databases to compile this review to pique the interest of researchers towards cancer metabolomics. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Strategies for Extending Metabolomics Studies with Stable Isotope Labelling and Fluxomics

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    Anubhav Srivastava

    2016-10-01

    Full Text Available This is a perspective from the peer session on stable isotope labelling and fluxomics at the Australian & New Zealand Metabolomics Conference (ANZMET held from 30 March to 1 April 2016 at La Trobe University, Melbourne, Australia. This report summarizes the key points raised in the peer session which focused on the advantages of using stable isotopes in modern metabolomics and the challenges in conducting flux analyses. The session highlighted the utility of stable isotope labelling in generating reference standards for metabolite identification, absolute quantification, and in the measurement of the dynamic activity of metabolic pathways. The advantages and disadvantages of different approaches of fluxomics analyses including flux balance analysis, metabolic flux analysis and kinetic flux profiling were also discussed along with the use of stable isotope labelling in in vivo dynamic metabolomics. A number of crucial technical considerations for designing experiments and analyzing data with stable isotope labelling were discussed which included replication, instrumentation, methods of labelling, tracer dilution and data analysis. This report reflects the current viewpoint on the use of stable isotope labelling in metabolomics experiments, identifying it as a great tool with the potential to improve biological interpretation of metabolomics data in a number of ways.

  19. Metabolomics-assisted biotechnological interventions for developing plant-based functional foods and nutraceuticals.

    Science.gov (United States)

    Kumar, Arun; Mosa, Kareem A; Ji, Liyao; Kage, Udaykumar; Dhokane, Dhananjay; Karre, Shailesh; Madalageri, Deepa; Pathania, Neemisha

    2017-03-08

    Today, the dramatic changes in types of food consumed have led to an increased burden of chronic diseases. Therefore, the emphasis of food research is not only to ensure quality food that can supply adequate nutrients to prevent nutrition related diseases, but also to ensure overall physical and mental-health. This has led to the concept of functional foods and nutraceuticals (FFNs), which can be ideally produced and delivered through plants. Metabolomics can help in getting the most relevant functional information, and thus has been considered the greatest -OMICS technology to date. However, metabolomics has not been exploited to the best potential in plant sciences. The technology can be leveraged to identify the health promoting compounds and metabolites that can be used for the development of FFNs. This article reviews (i) plant-based FFNs-related metabolites and their health benefits; (ii) use of different analytic platforms for targeted and non-targeted metabolite profiling along with experimental considerations; (iii) exploitation of metabolomics to develop FFNs in plants using various biotechnological tools; and (iv) potential use of metabolomics in plant breeding. We have also provided some insights into integration of metabolomics with latest genome editing tools for metabolic pathway regulation in plants.

  20. A Nontargeted UHPLC-HRMS Metabolomics Pipeline for Metabolite Identification: Application to Cardiac Remote Ischemic Preconditioning.

    Science.gov (United States)

    Kouassi Nzoughet, Judith; Bocca, Cinzia; Simard, Gilles; Prunier-Mirebeau, Delphine; Chao de la Barca, Juan Manuel; Bonneau, Dominique; Procaccio, Vincent; Prunier, Fabrice; Lenaers, Guy; Reynier, Pascal

    2017-02-07

    In recent years, the number of investigations based on nontargeted metabolomics has increased, although often without a thorough assessment of analytical strategies applied to acquire data. Following published guidelines for metabolomics experiments, we report a validated nontargeted metabolomics strategy with pipeline for unequivocal identification of metabolites using the MSMLS molecule library. We achieved an in-house database containing accurate m/z values, retention times, isotopic patterns, full MS, and MS/MS spectra. A UHPLC-HRMS Q-Exactive method was developed, and experimental variations were determined within and between 3 experimental days. The extraction efficiency as well as the accuracy, precision, repeatability, and linearity of the method were assessed, the method demonstrating good performances. The methodology was further blindly applied to plasma from remote ischemic pre-conditioning (RIPC) rats. Samples, previously analyzed by targeted metabolomics using completely different protocol, analytical strategy, and platform, were submitted to our analytical pipeline. A combination of multivariate and univariate statistical analyses was employed. Selection of putative biomarkers from OPLS-DA model and S-plot was combined to jack-knife confidence intervals, metabolites' VIP values, and univariate statistics. Only variables with strong model contribution and highly statistical reliability were selected as discriminated metabolites. Three biomarkers identified by the previous targeted metabolomics study were found in the current work, in addition to three novel metabolites, emphasizing the efficiency of the current methodology and its ability to identify new biomarkers of clinical interest, in a single sequence. The biomarkers were identified to level 1 according to the metabolomics standard initiative and confirmed by both RPLC and HILIC-HRMS.

  1. Metabolomic derangements are associated with mortality in critically ill adult patients.

    Science.gov (United States)

    Rogers, Angela J; McGeachie, Michael; Baron, Rebecca M; Gazourian, Lee; Haspel, Jeffrey A; Nakahira, Kiichi; Fredenburgh, Laura E; Hunninghake, Gary M; Raby, Benjamin A; Matthay, Michael A; Otero, Ronny M; Fowler, Vance G; Rivers, Emanuel P; Woods, Christopher W; Kingsmore, Stephen; Langley, Ray J; Choi, Augustine M K

    2014-01-01

    To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults. Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible. We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study. We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations). Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill

  2. Metabolomic derangements are associated with mortality in critically ill adult patients.

    Directory of Open Access Journals (Sweden)

    Angela J Rogers

    Full Text Available To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU mortality in adults.Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible.We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI. We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD study.We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05. Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05 in the CAPSOD population. Replicating metabolites included lipids (N = 14, amino acids or amino acid breakdown products (N = 12, carbohydrates (N = 1, nucleotides (N = 3, and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4, taurochenodeoxycholate, 3-(4-hydroxyphenyl lactate, sucrose, kynurenine. This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations.Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill

  3. Effects of Pu-erh ripened tea on hyperuricemic mice studied by serum metabolomics.

    Science.gov (United States)

    Zhao, Ran; Chen, Dong; Wu, Hualing

    2017-11-15

    To evaluate effects of Pu-erh ripened tea in hyperuricemic mice, a mouse hyperuricemia model was developed by oral administration of potassium oxonate for 7 d. Serum metabolomics, based on gas chromatography-mass spectrometry, was used to generate metabolic profiles from normal control, hyperuricemic and allopurinol-treated hyperuricemic mice, as well as hyperuricemic mice given Pu-erh ripened tea at three doses. Pu-erh ripened tea significantly lowered serum uric acid levels. Twelve potential biomarkers associated with hyperuricemia were identified. Pu-erh ripened tea and allopurinol differed in their metabolic effects in the hyperuricemic mice. Levels of glutamic acid, indolelactate, L-allothreonine, nicotinoylglycine, isoleucine, l-cysteine and glycocyamine, all involved in amino acid metabolism, were significantly changed in hyperuricemic mice treated Pu-erh ripened tea. Thus, modulating amino acid metabolism might be the primary mechanism of anti-hyperuricemia by Pu-erh ripened tea. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The dental calculus metabolome in modern and historic samples

    DEFF Research Database (Denmark)

    Velsko, Irina M.; Overmyer, Katherine A.; Speller, Camilla

    2017-01-01

    Introduction: Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction...... in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. Objective: We...... present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. Methods: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including...

  5. Biomarkers for predicting type 2 diabetes development — Can metabolomics improve on existing biomarkers?

    DEFF Research Database (Denmark)

    Savolainen, Otto; Fagerberg, Björn; Lind, Mads Vendelbo

    2017-01-01

    Aim The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers. Methods Gas chromatography-tandem mass spectrometry metabolomics was used in a nested case-control study based...... on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years followup. The metabolomics results were used as a standalone prediction...... model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D. Results Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin...

  6. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review

    Science.gov (United States)

    Background: Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD). Methods and Results: We searched MEDLINE and EMBASE from inception to Janua...

  7. Plant Metabolomics : the missiong link in functional genomics strategies

    NARCIS (Netherlands)

    Hall, R.D.; Beale, M.; Fiehn, O.; Hardy, N.; Summer, L.; Bino, R.

    2002-01-01

    After the establishment of technologies for high-throughput DNA sequencing (genomics), gene expression analysis (transcriptomics), and protein analysis (proteomics), the remaining functional genomics challenge is that of metabolomics. Metabolomics is the term coined for essentially comprehensive,

  8. NMR and pattern recognition methods in metabolomics: From data acquisition to biomarker discovery: A review

    Energy Technology Data Exchange (ETDEWEB)

    Smolinska, Agnieszka, E-mail: A.Smolinska@science.ru.nl [Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen (Netherlands); Blanchet, Lionel [Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen (Netherlands); Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Buydens, Lutgarde M.C.; Wijmenga, Sybren S. [Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen (Netherlands)

    2012-10-31

    Highlights: Black-Right-Pointing-Pointer Procedures for acquisition of different biofluids by NMR. Black-Right-Pointing-Pointer Recent developments in metabolic profiling of different biofluids by NMR are presented. Black-Right-Pointing-Pointer The crucial steps involved in data preprocessing and multivariate chemometric analysis are reviewed. Black-Right-Pointing-Pointer Emphasis is given on recent findings on Multiple Sclerosis via NMR and pattern recognition methods. - Abstract: Metabolomics is the discipline where endogenous and exogenous metabolites are assessed, identified and quantified in different biological samples. Metabolites are crucial components of biological system and highly informative about its functional state, due to their closeness to functional endpoints and to the organism's phenotypes. Nuclear Magnetic Resonance (NMR) spectroscopy, next to Mass Spectrometry (MS), is one of the main metabolomics analytical platforms. The technological developments in the field of NMR spectroscopy have enabled the identification and quantitative measurement of the many metabolites in a single sample of biofluids in a non-targeted and non-destructive manner. Combination of NMR spectra of biofluids and pattern recognition methods has driven forward the application of metabolomics in the field of biomarker discovery. The importance of metabolomics in diagnostics, e.g. in identifying biomarkers or defining pathological status, has been growing exponentially as evidenced by the number of published papers. In this review, we describe the developments in data acquisition and multivariate analysis of NMR-based metabolomics data, with particular emphasis on the metabolomics of Cerebrospinal Fluid (CSF) and biomarker discovery in Multiple Sclerosis (MScl).

  9. Could exercise metabolomics pave the way for gymnomimetics?

    Science.gov (United States)

    Burke, Megan F; Dunbar, Richard L; Rader, Daniel J

    2010-07-21

    Regular physical activity and especially aerobic exercise are associated with reduced risk of disease and enhanced longevity, but the molecular mechanisms of these health benefits remain obscure. A comprehensive metabolomic approach was used to characterize the changes in blood levels of >200 metabolites upon vigorous exercise and identified two dozen that changed substantially. One, niacinamide, is intimately related to the metabolism of nicotinamide adenine dinucleotide (NAD(+)) and its reduced form NADH, which is in turn linked with exercise capacity as well as health status. Intensive investigation of metabolic changes with exercise could lead to pharmacological attempts to mimic the beneficial effects of exercise, an approach we term "gymnomimetics."

  10. Metabolomics data normalization with EigenMS.

    Directory of Open Access Journals (Sweden)

    Yuliya V Karpievitch

    Full Text Available Liquid chromatography mass spectrometry has become one of the analytical platforms of choice for metabolomics studies. However, LC-MS metabolomics data can suffer from the effects of various systematic biases. These include batch effects, day-to-day variations in instrument performance, signal intensity loss due to time-dependent effects of the LC column performance, accumulation of contaminants in the MS ion source and MS sensitivity among others. In this study we aimed to test a singular value decomposition-based method, called EigenMS, for normalization of metabolomics data. We analyzed a clinical human dataset where LC-MS serum metabolomics data and physiological measurements were collected from thirty nine healthy subjects and forty with type 2 diabetes and applied EigenMS to detect and correct for any systematic bias. EigenMS works in several stages. First, EigenMS preserves the treatment group differences in the metabolomics data by estimating treatment effects with an ANOVA model (multiple fixed effects can be estimated. Singular value decomposition of the residuals matrix is then used to determine bias trends in the data. The number of bias trends is then estimated via a permutation test and the effects of the bias trends are eliminated. EigenMS removed bias of unknown complexity from the LC-MS metabolomics data, allowing for increased sensitivity in differential analysis. Moreover, normalized samples better correlated with both other normalized samples and corresponding physiological data, such as blood glucose level, glycated haemoglobin, exercise central augmentation pressure normalized to heart rate of 75, and total cholesterol. We were able to report 2578 discriminatory metabolite peaks in the normalized data (p<0.05 as compared to only 1840 metabolite signals in the raw data. Our results support the use of singular value decomposition-based normalization for metabolomics data.

  11. Serum metabolomics reveals betaine and phosphatidylcholine as potential biomarkers for the toxic responses of processed Aconitum carmichaelii Debx.

    Science.gov (United States)

    Tan, Yong; Ko, Joshua; Liu, Xinru; Lu, Cheng; Li, Jian; Xiao, Cheng; Li, Li; Niu, Xuyan; Jiang, Miao; He, Xiaojuan; Zhao, Hongyan; Zhang, Zhongxiao; Bian, Zhaoxiang; Yang, Zhijun; Zhang, Ge; Zhang, Weidong; Lu, Aiping

    2014-07-29

    We recently reported that processed Aconitum carmichaelii Debx (Bai-Fu-Pian in Chinese, BFP) elicits differential toxic responses in rats under various health conditions. The present study aimed to determine the graded toxicity of BFP so as to derive a safe therapeutic rationale in clinical practice. Sensitive and reliable biomarkers of toxicity were also identified, with the corresponding metabolic pathways being unveiled. Thirty male Sprague-Dawley rats were divided into five groups (n = 6) and received oral administration of BFP extract (0.32, 0.64, 1.28 or 2.56 g kg(-1) per day) or an equal volume of drinking water (control) for 15 days. The metabolomic profiles of rat serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry (LC-Q-TOF-MS). Linear regression analysis and Ingenuity Pathway Analysis (IPA) were used to elucidate the differentiated altered metabolites and associated network relationships. Results from biochemical and histopathological examinations revealed that BFP could induce prominent toxicity in the heart, liver and kidneys at a dose of 2.56 g kg(-1) per day. Betaine up-regulation and phosphatidylcholine down-regulation were detected in the serum samples of drug-treated groups in a dose-dependent manner. In summary, betaine and phosphatidylcholine could be regarded as sensitive biomarkers for the toxic responses of BFP. Perturbations of RhoA signaling, choline metabolism and free radical scavenging were found to be partly responsible for the toxic effects of the herbal drug. Based on the metabolomics findings, we could establish a safe therapeutic range in the clinical use of BFP, with promising predictions of possible drug toxicity.

  12. Identifying the association rules between clinicopathologic factors and higher survival performance in operation-centric oral cancer patients using the Apriori algorithm.

    Science.gov (United States)

    Tang, Jen-Yang; Chuang, Li-Yeh; Hsi, Edward; Lin, Yu-Da; Yang, Cheng-Hong; Chang, Hsueh-Wei

    2013-01-01

    This study computationally determines the contribution of clinicopathologic factors correlated with 5-year survival in oral squamous cell carcinoma (OSCC) patients primarily treated by surgical operation (OP) followed by other treatments. From 2004 to 2010, the program enrolled 493 OSCC patients at the Kaohsiung Medical Hospital University. The clinicopathologic records were retrospectively reviewed and compared for survival analysis. The Apriori algorithm was applied to mine the association rules between these factors and improved survival. Univariate analysis of demographic data showed that grade/differentiation, clinical tumor size, pathology tumor size, and OP grouping were associated with survival longer than 36 months. Using the Apriori algorithm, multivariate correlation analysis identified the factors that coexistently provide good survival rates with higher lift values, such as grade/differentiation = 2, clinical stage group = early, primary site = tongue, and group = OP. Without the OP, the lift values are lower. In conclusion, this hospital-based analysis suggests that early OP and other treatments starting from OP are the key to improving the survival of OSCC patients, especially for early stage tongue cancer with moderate differentiation, having a better survival (>36 months) with varied OP approaches.

  13. A functional genomics approach using metabolomics and in silico pathway analysis

    DEFF Research Database (Denmark)

    Förster, Jochen; Gombert, Andreas Karoly; Nielsen, Jens

    2002-01-01

    analysis techniques and changes in the genotype will in many cases lead to different metabolite profiles. Here, a theoretical framework that may be applied to identify the function of orphan genes is presented. The approach is based on a combination of metabolome analysis combined with in silico pathway...

  14. Metabolomic profiles delineate signature metabolic shifts during estrogen deficiency-induced bone loss in rat by GC-TOF/MS.

    Directory of Open Access Journals (Sweden)

    Bo Ma

    Full Text Available Postmenopausal osteoporosis is a complicated and multi-factorial disease. To study the metabolic profiles and pathways activated in osteoporosis, Eight rats were oophorectomized (OVX group to represent postmenopausal osteoporosis and the other eight rats were sham operated (Sham group to be the control. The biochemical changes were assessed with metabolomics using a gas chromatography/time-of-flight mass spectrometry. Metabolomic profile using serial blood samples obtained prior to and at different time intervals after OVX were analyzed by principal component analysis (PCA and Partial least squares-discriminant analysis (PLS-DA. The conventional indicators (bone mineral density, serum Bone alkaline phosphatase (B-ALP and N-telopeptide of type I collagen (NTx of osteoporosis in rats were also determined simultaneously. In OVX group, the metabolomics method could describe the endogenous changes of the disease more sensitively and systematically than the conventional criteria during the progression of osteoporosis. Significant metabolomic difference was also observed between the OVX and Sham groups. The metabolomic analyses of rat plasma showed that levels of arachidonic acid, octadecadienoic acid, branched-chain amino acids (valine, leucine and isoleucine, homocysteine, hydroxyproline and ketone bodies (3-Hydroxybutyric Acid significantly elevated, while levels of docosahexaenoic acid, dodecanoic acid and lysine significantly decreased in OVX group compared with those in the homeochronous Sham group. Considering such metabolites are closely related to the pathology of the postmenopausal osteoporosis, the results suggest that potential biomarkers for the early diagnosis or the pathogenesis of osteoporosis might be identified via metabolomic study.

  15. Serial Metabolome Changes in a Prospective Cohort of Subjects with Influenza Viral Infection and Comparison with Dengue Fever.

    Science.gov (United States)

    Cui, Liang; Fang, Jinling; Ooi, Eng Eong; Lee, Yie Hou

    2017-07-07

    Influenza virus infection (IVI) and dengue virus infection (DVI) are major public health threats. Between IVI and DVI, clinical symptoms can be overlapping yet infection-specific, but host metabolome changes are not well-described. Untargeted metabolomics and targeted oxylipinomic analyses were performed on sera serially collected at three phases of infection from a prospective cohort study of adult subjects with either H3N2 influenza infection or dengue fever. Untargeted metabolomics identified 26 differential metabolites, and major perturbed pathways included purine metabolism, fatty acid biosynthesis and β-oxidation, tryptophan metabolism, phospholipid catabolism, and steroid hormone pathway. Alterations in eight oxylipins were associated with the early symptomatic phase of H3N2 flu infection, were mostly arachidonic acid-derived, and were enriched in the lipoxygenase pathway. There was significant overlap in metabolome profiles in both infections. However, differences specific to IVI and DVI were observed. DVI specifically attenuated metabolites including serotonin, bile acids and biliverdin. Additionally, metabolome changes were more persistent in IVI in which metabolites such as hypoxanthine, inosine, and xanthine of the purine metabolism pathway remained significantly elevated at 21-27 days after fever onset. This study revealed the dynamic metabolome changes in IVI subjects and provided biochemical insights on host physiological similarities and differences between IVI and DVI.

  16. Fish mucus metabolome reveals fish life-history traits

    Science.gov (United States)

    Reverter, M.; Sasal, P.; Banaigs, B.; Lecchini, D.; Lecellier, G.; Tapissier-Bontemps, N.

    2017-06-01

    Fish mucus has important biological and ecological roles such as defense against fish pathogens and chemical mediation among several species. A non-targeted liquid chromatography-mass spectrometry metabolomic approach was developed to study gill mucus of eight butterflyfish species in Moorea (French Polynesia), and the influence of several fish traits (geographic site and reef habitat, species taxonomy, phylogeny, diet and parasitism levels) on the metabolic variability was investigated. A biphasic extraction yielding two fractions (polar and apolar) was used. Fish diet (obligate corallivorous, facultative corallivorous or omnivorous) arose as the main driver of the metabolic differences in the gill mucus in both fractions, accounting for 23% of the observed metabolic variability in the apolar fraction and 13% in the polar fraction. A partial least squares discriminant analysis allowed us to identify the metabolites (variable important in projection, VIP) driving the differences between fish with different diets (obligate corallivores, facultative corallivores and omnivorous). Using accurate mass data and fragmentation data, we identified some of these VIP as glycerophosphocholines, ceramides and fatty acids. Level of monogenean gill parasites was the second most important factor shaping the gill mucus metabolome, and it explained 10% of the metabolic variability in the polar fraction and 5% in the apolar fraction. A multiple regression tree revealed that the metabolic variability due to parasitism in the polar fraction was mainly due to differences between non-parasitized and parasitized fish. Phylogeny and butterflyfish species were factors contributing significantly to the metabolic variability of the apolar fraction (10 and 3%, respectively) but had a less pronounced effect in the polar fraction. Finally, geographic site and reef habitat of butterflyfish species did not influence the gill mucus metabolome of butterflyfishes.

  17. Metabolomics: towards understanding traditional Chinese medicine.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Wang, Zhigang; Sun, Wenjun; Wang, Ping; Wang, Xijun

    2010-12-01

    Metabolomics represent a global understanding of metabolite complement of integrated living systems and dynamic responses to the changes of both endogenous and exogenous factors and has many potential applications and advantages for the research of complex systems. As a systemic approach, metabolomics adopts a "top-down" strategy to reflect the function of organisms from the end products of the metabolic network and to understand metabolic changes of a complete system caused by interventions in a holistic context. This property agrees with the holistic thinking of Traditional Chinese Medicine (TCM), a complex medical science, suggesting that metabolomics has the potential to impact our understanding of the theory behind the evidence-based Chinese medicine. Consequently, the development of robust metabolomic platforms will greatly facilitate, for example, the understanding of the action mechanisms of TCM formulae and the analysis of Chinese herbal (CHM) and mineral medicine, acupuncture, and Chinese medicine syndromes. This review summarizes some of the applications of metabolomics in special TCM issues with an emphasis on metabolic biomarker discovery. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Basics of mass spectrometry based metabolomics.

    Science.gov (United States)

    Courant, Frédérique; Antignac, Jean-Philippe; Dervilly-Pinel, Gaud; Le Bizec, Bruno

    2014-11-01

    The emerging field of metabolomics, aiming to characterize small molecule metabolites present in biological systems, promises immense potential for different areas such as medicine, environmental sciences, agronomy, etc. The purpose of this article is to guide the reader through the history of the field, then through the main steps of the metabolomics workflow, from study design to structure elucidation, and help the reader to understand the key phases of a metabolomics investigation and the rationale underlying the protocols and techniques used. This article is not intended to give standard operating procedures as several papers related to this topic were already provided, but is designed as a tutorial aiming to help beginners understand the concept and challenges of MS-based metabolomics. A real case example is taken from the literature to illustrate the application of the metabolomics approach in the field of doping analysis. Challenges and limitations of the approach are then discussed along with future directions in research to cope with these limitations. This tutorial is part of the International Proteomics Tutorial Programme (IPTP18). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. An oral keratinocyte life cycle model identifies novel host genome regulation by human papillomavirus 16 relevant to HPV positive head and neck cancer

    OpenAIRE

    Evans, Michael R.; James, Claire D.; Loughran, Oonagh; Nulton, Tara J.; Wang, Xu; Bristol, Molly L.; Windle, Brad; Morgan, Iain M.

    2017-01-01

    Many aspects of the HPV life cycle have been characterized in cervical cell lines (W12, CIN612) and in HPV immortalized primary foreskin keratinocytes. There is now an epidemic of HPV positive oropharyngeal cancers (HPV16 is responsible for 80-90% of these); therefore increased understanding of the HPV16 life cycle in oral keratinocytes is a priority. To date there have been limited reports characterizing the HPV16 life cycle in oral keratinocytes. Using TERT immortalized “normal” oral kerati...

  20. Preanalytical aspects and sample quality assessment in metabolomics studies of human blood.

    Science.gov (United States)

    Yin, Peiyuan; Peter, Andreas; Franken, Holger; Zhao, Xinjie; Neukamm, Sabine S; Rosenbaum, Lars; Lucio, Marianna; Zell, Andreas; Häring, Hans-Ulrich; Xu, Guowang; Lehmann, Rainer

    2013-05-01

    Metabolomics is a powerful tool that is increasingly used in clinical research. Although excellent sample quality is essential, it can easily be compromised by undetected preanalytical errors. We set out to identify critical preanalytical steps and biomarkers that reflect preanalytical inaccuracies. We systematically investigated the effects of preanalytical variables (blood collection tubes, hemolysis, temperature and time before further processing, and number of freeze-thaw cycles) on metabolomics studies of clinical blood and plasma samples using a nontargeted LC-MS approach. Serum and heparinate blood collection tubes led to chemical noise in the mass spectra. Distinct, significant changes of 64 features in the EDTA-plasma metabolome were detected when blood was exposed to room temperature for 2, 4, 8, and 24 h. The resulting pattern was characterized by increases in hypoxanthine and sphingosine 1-phosphate (800% and 380%, respectively, at 2 h). In contrast, the plasma metabolome was stable for up to 4 h when EDTA blood samples were immediately placed in iced water. Hemolysis also caused numerous changes in the metabolic profile. Unexpectedly, up to 4 freeze-thaw cycles only slightly changed the EDTA-plasma metabolome, but increased the individual variability. Nontargeted metabolomics investigations led to the following recommendations for the preanalytical phase: test the blood collection tubes, avoid hemolysis, place whole blood immediately in ice water, use EDTA plasma, and preferably use nonrefrozen biobank samples. To exclude outliers due to preanalytical errors, inspect the biomarker signal intensities reflecting systematic as well as accidental and preanalytical inaccuracies before processing the bioinformatics data. © 2013 American Association for Clinical Chemistry.

  1. MetabR: an R script for linear model analysis of quantitative metabolomic data

    Directory of Open Access Journals (Sweden)

    Ernest Ben

    2012-10-01

    Full Text Available Abstract Background Metabolomics is an emerging high-throughput approach to systems biology, but data analysis tools are lacking compared to other systems level disciplines such as transcriptomics and proteomics. Metabolomic data analysis requires a normalization step to remove systematic effects of confounding variables on metabolite measurements. Current tools may not correctly normalize every metabolite when the relationships between each metabolite quantity and fixed-effect confounding variables are different, or for the effects of random-effect confounding variables. Linear mixed models, an established methodology in the microarray literature, offer a standardized and flexible approach for removing the effects of fixed- and random-effect confounding variables from metabolomic data. Findings Here we present a simple menu-driven program, “MetabR”, designed to aid researchers with no programming background in statistical analysis of metabolomic data. Written in the open-source statistical programming language R, MetabR implements linear mixed models to normalize metabolomic data and analysis of variance (ANOVA to test treatment differences. MetabR exports normalized data, checks statistical model assumptions, identifies differentially abundant metabolites, and produces output files to help with data interpretation. Example data are provided to illustrate normalization for common confounding variables and to demonstrate the utility of the MetabR program. Conclusions We developed MetabR as a simple and user-friendly tool for implementing linear mixed model-based normalization and statistical analysis of targeted metabolomic data, which helps to fill a lack of available data analysis tools in this field. The program, user guide, example data, and any future news or updates related to the program may be found at http://metabr.r-forge.r-project.org/.

  2. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease

    Directory of Open Access Journals (Sweden)

    Robert A. Quinn

    2016-08-01

    Full Text Available Background. Cystic fibrosis (CF is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS. The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable. Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset.

  3. Metabolomic changes in follicular fluid induced by soy isoflavones administered to rats from weaning until sexual maturity

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wenxiang [Department of Nutrition and Health Care, School of Public Health, Fujian Medical University, Fuzhou, Fujian (China); Zhang, Wenchang, E-mail: wenchang2002@sina.com [Department of Occupational and Environmental Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian (China); Liu, Jin [Department of Occupational and Environmental Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian (China); Sun, Yan [Center for Reproductive Medicine, Teaching Hospital of Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian (China); Li, Yuchen; Li, Hong; Xiao, Shihua; Shen, Xiaohua [Department of Occupational and Environmental Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian (China)

    2013-06-15

    Female Wistar rats at 21 days of age were treated with one of three concentrations of soy isoflavones (SIF) (50, 100 or 200 mg/kg body weight, orally, once per day) from weaning until sexual maturity (3 months) in order to evaluate the influence of SIF on ovarian follicle development. After treatment, the serum sex hormone levels and enumeration of ovarian follicles of the ovary were measured. The metabolic profile of follicular fluid was determined using HPLC-MS. Principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was used to identify differences in metabolites and reveal useful toxic biomarkers. The results indicated that modest doses of SIF affect ovarian follicle development, as demonstrated by decreased serum estradiol levels and increases in both ovarian follicle atresia and corpora lutea number in the ovary. SIF treatment-related metabolic alterations in follicular fluid were also found in the PCA and PLS-DA models. The 24 most significantly altered metabolites were identified, including primary sex hormones, amino acids, fatty acids and metabolites involved in energy metabolism. These findings may indicate that soy isoflavones affect ovarian follicle development by inducing metabolomic variations in the follicular fluid. - Highlights: ► Modest doses of soy isoflavones (SIF) do affect ovarian follicle development. ► SIF treatment-related metabolic alterations in follicular fluid were found. ► The 24 most significantly altered metabolites were identified.

  4. Metabolomic changes in follicular fluid induced by soy isoflavones administered to rats from weaning until sexual maturity

    International Nuclear Information System (INIS)

    Wang, Wenxiang; Zhang, Wenchang; Liu, Jin; Sun, Yan; Li, Yuchen; Li, Hong; Xiao, Shihua; Shen, Xiaohua

    2013-01-01

    Female Wistar rats at 21 days of age were treated with one of three concentrations of soy isoflavones (SIF) (50, 100 or 200 mg/kg body weight, orally, once per day) from weaning until sexual maturity (3 months) in order to evaluate the influence of SIF on ovarian follicle development. After treatment, the serum sex hormone levels and enumeration of ovarian follicles of the ovary were measured. The metabolic profile of follicular fluid was determined using HPLC-MS. Principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was used to identify differences in metabolites and reveal useful toxic biomarkers. The results indicated that modest doses of SIF affect ovarian follicle development, as demonstrated by decreased serum estradiol levels and increases in both ovarian follicle atresia and corpora lutea number in the ovary. SIF treatment-related metabolic alterations in follicular fluid were also found in the PCA and PLS-DA models. The 24 most significantly altered metabolites were identified, including primary sex hormones, amino acids, fatty acids and metabolites involved in energy metabolism. These findings may indicate that soy isoflavones affect ovarian follicle development by inducing metabolomic variations in the follicular fluid. - Highlights: ► Modest doses of soy isoflavones (SIF) do affect ovarian follicle development. ► SIF treatment-related metabolic alterations in follicular fluid were found. ► The 24 most significantly altered metabolites were identified

  5. Identifying Low pH Active and Lactate-Utilizing Taxa within Oral Microbiome Communities from Healthy Children Using Stable Isotope Probing Techniques

    Energy Technology Data Exchange (ETDEWEB)

    McLean, Jeffrey S.; Fansler, Sarah J.; Majors, Paul D.; Mcateer, Kathleen; Allen, Lisa Z.; Shirtliff, Mark E.; Lux, Renate; Shi, Wenyuan

    2012-03-05

    Many human microbial infectious diseases including dental caries are polymicrobial in nature and how these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral microbes have been characterized in vitro, their physiology in vivo in the presence of the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these oral species remain uncultivated to date and little is known except their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated microorganisms will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a novel combination of in vivo Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for temporal monitoring of carbohydrate utilization, organic acid production and identification of metabolically active and inactive bacterial species.

  6. Microbiome, Metabolome and Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Ishfaq Ahmed

    2016-06-01

    Full Text Available Inflammatory Bowel Disease (IBD is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD or Ulcerative Colitis (UC, two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis.

  7. Metabolomics in pediatric nephrology: Emerging concepts

    Science.gov (United States)

    Hanna, Mina H; Brophy, Patrick D

    2014-01-01

    Metabolomics, the latest of the “omics” sciences, refers to the systematic study of metabolites and their changes in biological samples due to physiological stimuli and/or genetic modification. Because metabolites represent the downstream expression of genome, transcriptome and proteome, they can closely reflect the phenotype of an organism at a specific time. As an emerging field in analytical biochemistry; metabolomics has the potential to play a major role for monitoring real-time kidney function and detecting adverse renal events. Additionally, small molecule metabolites can provide mechanistic insights for novel biomarkers of kidney diseases, given the limitations of the current traditional markers. The clinical utility of metabolomics in the field of pediatric nephrology includes biomarker discovery, defining as yet unrecognized biologic therapeutic targets, linking of metabolites to relevant standard indices and clinical outcomes, and providing a window of opportunity to investigate the intricacies of environment/genetic interplay in specific disease states. PMID:25027575

  8. Assessment of children's nutritional attitudes before oral food challenges to identify patients at risk of food reintroduction failure: a prospective study.

    Science.gov (United States)

    Polloni, L; Ferruzza, E; Ronconi, L; Toniolo, A; Lazzarotto, F; Bonaguro, R; Celegato, N; Muraro, A

    2017-05-01

    Inappropriate dietary eliminations may impair quality of life, affect children's growth and unnecessarily impact on healthcare costs. Previous retrospective studies reported that around 25% of children continue a food-avoidance diet despite a negative oral food challenge (OFC). A definite pattern has not been found yet for patients not reintroducing the food. This study aimed to examine the role of child's nutritional attitudes and maternal anxiety in reintroducing food after a negative OFC. A prospective study was conducted involving 81 mothers of children with IgE-mediated food allergy. They completed a survey on nutritional behaviour and attitudes and the State-Trait Anxiety Inventory on the day of OFC and 6 months later. In total, 11.1% of children never or rarely ate the food after a negative OFC. Consumption of the reintroduced food is positively correlated to child's interest in tasting new foods before and after OFC and to changes in child's nutritional habits after OFC. It is negatively correlated to monotony of the diet after OFC. No correlations were found with other participants' characteristics or maternal anxiety. State anxiety significantly decreased after the OFC. A correlation was found between trait and state anxiety and the degree of change in nutritional habits after OFC. Evaluating child's approach towards food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Linking metabolomics data to underlying metabolic regulation

    Directory of Open Access Journals (Sweden)

    Thomas eNägele

    2014-11-01

    Full Text Available The comprehensive experimental analysis of a metabolic constitution plays a central role in approaches of organismal systems biology.Quantifying the impact of a changing environment on the homeostasis of cellular metabolism has been the focus of numerous studies applying various metabolomics techniques. It has been proven that approaches which integrate different analytical techniques, e.g. LC-MS, GC-MS, CE-MS and H-NMR, can provide a comprehensive picture of a certain metabolic homeostasis. Identification of metabolic compounds and quantification of metabolite levels represent the groundwork for the analysis of regulatory strategies in cellular metabolism. This significantly promotes our current understanding of the molecular organization and regulation of cells, tissues and whole organisms.Nevertheless, it is demanding to elicit the pertinent information which is contained in metabolomics data sets.Based on the central dogma of molecular biology, metabolite levels and their fluctuations are the result of a directed flux of information from gene activation over transcription to translation and posttranslational modification.Hence, metabolomics data represent the summed output of a metabolic system comprising various levels of molecular organization.As a consequence, the inverse assignment of metabolomics data to underlying regulatory processes should yield information which-if deciphered correctly-provides comprehensive insight into a metabolic system.Yet, the deduction of regulatory principles is complex not only due to the high number of metabolic compounds, but also because of a high level of cellular compartmentalization and differentiation.Motivated by the question how metabolomics approaches can provide a representative view on regulatory biochemical processes, this article intends to present and discuss current metabolomics applications, strategies of data analysis and their limitations with respect to the interpretability in context of

  10. MBRole: enrichment analysis of metabolomic data.

    Science.gov (United States)

    Chagoyen, Monica; Pazos, Florencio

    2011-03-01

    While many tools exist for performing enrichment analysis of transcriptomic and proteomic data in order to interpret them in biological terms, almost no equivalent tools exist for metabolomic data. We present Metabolite Biological Role (MBRole), a web server for carrying out over-representation analysis of biological and chemical annotations in arbitrary sets of metabolites (small chemical compounds) coming from metabolomic data of any organism or sample. The web server is freely available at http://csbg.cnb.csic.es/mbrole. It was tested in the main web browsers.

  11. Towards a scientific interpretation of the terroir concept: plasticity of the grape berry metabolome.

    Science.gov (United States)

    Anesi, Andrea; Stocchero, Matteo; Dal Santo, Silvia; Commisso, Mauro; Zenoni, Sara; Ceoldo, Stefania; Tornielli, Giovanni Battista; Siebert, Tracey E; Herderich, Markus; Pezzotti, Mario; Guzzo, Flavia

    2015-08-07

    The definition of the terroir concept is one of the most debated issues in oenology and viticulture. The dynamic interaction among diverse factors including the environment, the grapevine plant and the imposed viticultural techniques means that the wine produced in a given terroir is unique. However, there is an increasing interest to define and quantify the contribution of individual factors to a specific terroir objectively. Here, we characterized the metabolome and transcriptome of berries from a single clone of the Corvina variety cultivated in seven different vineyards, located in three macrozones, over a 3-year trial period. To overcome the anticipated strong vintage effect, we developed statistical tools that allowed us to identify distinct terroir signatures in the metabolic composition of berries from each macrozone, and from different vineyards within each macrozone. We also identified non-volatile and volatile components of the metabolome which are more plastic and therefore respond differently to terroir diversity. We observed some relationships between the plasticity of the metabolome and transcriptome, allowing a multifaceted scientific interpretation of the terroir concept. Our experiments with a single Corvina clone in different vineyards have revealed the existence of a clear terroir-specific effect on the transcriptome and metabolome which persists over several vintages and allows each vineyard to be characterized by the unique profile of specific metabolites.

  12. Metabolic Mechanism for l-Leucine-Induced Metabolome To Eliminate Streptococcus iniae.

    Science.gov (United States)

    Du, Chao-Chao; Yang, Man-Jun; Li, Min-Yi; Yang, Jun; Peng, Bo; Li, Hui; Peng, Xuan-Xian

    2017-05-05

    Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for l-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC-MS-based metabolomics was used to investigate the tilapia liver metabolic profile in the presence of exogenous l-leucine. Thirty-seven metabolites of differential abundance were determined, and 11 metabolic pathways were enriched. Pattern recognition analysis identified serine and proline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting that the two metabolites play crucial roles in l-leucine-induced elimination of the pathogen by the host. Exogenous l-serine reduces the mortality of tilapias infected by S. iniae, providing a robust proof supporting the conclusion. Furthermore, exogenous l-serine elevates expression of genes IL-1β and IL-8 in tilapia spleen, but not TNFα, CXCR4 and Mx, suggesting that the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that l-leucine promotes macrophages to kill both Gram-positive and Gram-negative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous l-leucine is partly attributed to elevation of l-serine. These results demonstrate a metabolic mechanism by which exogenous l-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens.

  13. A Distinctive Urinary Metabolomic Fingerprint Is Linked With Endoscopic Postoperative Disease Recurrence in Crohn's Disease Patients.

    Science.gov (United States)

    Keshteli, Ammar Hassanzadeh; Tso, Robert; Dieleman, Levinus A; Park, Heekuk; Kroeker, Karen I; Jovel, Juan; Gillevet, Patrick M; Sikaroodi, Masoumeh; Mandal, Rupasri; Fedorak, Richard N; Madsen, Karen L

    2018-03-19

    Crohn's disease (CD) patients who undergo ileocolonic resection frequently have disease recurrence. The aim of this preliminary study was to identify urinary metabolomic profiles associated with disease recurrence in order to identify underlying mechanisms of recurrence and possible disease biomarkers. Biopsies from the neoterminal ileum were collected from CD patients (n = 38) after ileocolonic resection in order to assess mucosa-associated microbiota using 16S rRNA multitag pyrosequencing. Urine samples were collected, and metabolomic profiling was done using high-resolution nuclear magnetic resolution spectroscopy and a combined direct infusion liquid chromatography tandem mass spectrometry. The Rutgeerts scoring system was used to assess endoscopic postoperative recurrence of CD. There were 28 (73.7%) patients with endoscopic CD recurrence. CD patients who were in endoscopic remission had a higher abundance of Bacteroidetes and lower abundance of Fusobacteria and Proteobacteria in comparison with CD patients who had endoscopic recurrence. In addition, metabolomic profiling could also discriminate between these 2 groups of patients. Endoscopic recurrence was associated with increased concentration of urinary levoglucosan. Rutgeerts score was positively correlated with levoglucosan and propylene glycol levels. CD patients who present with endoscopic disease recurrence after surgery have a unique urinary metabolomic fingerprint that can differentiate them from CD patients who are in endoscopic remission after ileocolonic resection. In addition, mucosal-associated microbiota in CD patients with or without disease recurrence after surgery differs and correlates with some urinary metabolites.

  14. Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA.

    Science.gov (United States)

    Cecatti, Jose G; Souza, Renato T; Sulek, Karolina; Costa, Maria L; Kenny, Louise C; McCowan, Lesley M; Pacagnella, Rodolfo C; Villas-Boas, Silas G; Mayrink, Jussara; Passini, Renato; Franchini, Kleber G; Baker, Philip N

    2016-08-08

    Spontaneous preterm birth is a complex syndrome with multiple pathways interactions determining its occurrence, including genetic, immunological, physiologic, biochemical and environmental factors. Despite great worldwide efforts in preterm birth prevention, there are no recent effective therapeutic strategies able to decrease spontaneous preterm birth rates or their consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate metabolomics technologies to identify clinical and metabolite predictors for preterm birth. These innovative and unbiased techniques might be a strategic key to advance spontaneous preterm birth prediction. Preterm SAMBA study consists of a discovery phase to identify biophysical and untargeted metabolomics from blood and hair samples associated with preterm birth, plus a validation phase to evaluate the performance of the predictive modelling. The first phase, a case-control study, will randomly select 100 women who had a spontaneous preterm birth (before 37 weeks) and 100 women who had term birth in the Cork Ireland and Auckland New Zealand cohorts within the SCOPE study, an international consortium aimed to identify potential metabolomic predictors using biophysical data and blood samples collected at 20 weeks of gestation. The validation phase will recruit 1150 Brazilian pregnant women from five participant centres and will collect blood and hair samples at 20 weeks of gestation to evaluate the performance of the algorithm model (sensitivity, specificity, predictive values and likelihood ratios) in predicting spontaneous preterm birth (before 34 weeks, with a secondary analysis of delivery before 37 weeks). The Preterm SAMBA study intends to step forward on preterm birth prediction using metabolomics techniques, and accurate protocols for sample collection among multi-ethnic populations. The use of metabolomics in medical science research is innovative and promises to provide solutions for disorders with multiple

  15. Metabolomics coupled with similarity analysis advances the elucidation of the cold/hot properties of traditional Chinese medicines.

    Science.gov (United States)

    Jia, Yan; Zhang, Zheng-Zheng; Wei, Yu-Hai; Xue-Mei, Qin; Li, Zhen-Yu

    2017-08-01

    It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine (TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance (NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  16. Oral health: equity and social determinants

    DEFF Research Database (Denmark)

    Kwan, Stella; Petersen, Poul Erik

    2010-01-01

    This book chapter discusses the social determinants of oral health, and identifies interventions that have been, or can be, used in addressing oral health inequities (e.g. oral health promotion, education programmes, improving access to oral health care)....

  17. Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal

    Energy Technology Data Exchange (ETDEWEB)

    Karimpour, Masoumeh; Surowiec, Izabella; Wu, Junfang [Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 90187 Umeå (Sweden); Gouveia-Figueira, Sandra [Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 90187 Umeå (Sweden); Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå (Sweden); Pinto, Rui [Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 90187 Umeå (Sweden); Bioinformatics Infrastructure for Life Sciences (Sweden); Trygg, Johan [Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 90187 Umeå (Sweden); Zivkovic, Angela M. [Department of Nutrition, University of California, Davis, One Shields Ave, CA 95616 (United States); Nording, Malin L., E-mail: malin.nording@umu.se [Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 90187 Umeå (Sweden)

    2016-02-18

    The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms – gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) – to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1–86% for GC-MS and 0.9–42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2–97% for the positive and 4–69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a

  18. Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal

    International Nuclear Information System (INIS)

    Karimpour, Masoumeh; Surowiec, Izabella; Wu, Junfang; Gouveia-Figueira, Sandra; Pinto, Rui; Trygg, Johan; Zivkovic, Angela M.; Nording, Malin L.

    2016-01-01

    The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms – gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) – to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1–86% for GC-MS and 0.9–42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2–97% for the positive and 4–69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a

  19. Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

    International Nuclear Information System (INIS)

    Xu, Ming-Yuan; Wang, Pan; Sun, Ying-Jian; Wu, Yi-Jun

    2017-01-01

    Pesticides and heavy metals are widespread environmental pollutants. Although the acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd, especially the hepatotoxicity of the two chemicals with long-term exposure at a low dose, remained unclear. In this study, we investigated the toxicity in the liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant doses. Rats were given three different doses (1/135 LD 50 , 1/45 LD 50 and 1/15 LD 50 ) of CPF and Cd as well as their mixtures by oral gavage for 90 days. After treatment, the liver tissues were subjected to histopathological examination and biochemical analysis. Gas chromatography-mass spectrometry (GC–MS) was used to analyze the metabolomic changes in the rat liver upon CPF, Cd and their mixtures treatment. The results showed that CPF and Cd-induced oxidative damage and disrupted energy, amino acid, and fatty acid metabolism in the liver. Eleven biomarkers in liver were identified for CPF-, Cd-, and their mixture-treated rats. Three metabolites, i.e., butanedioic acid, myo-inositol, and urea, were identified as unique biomarkers for the mixture-treated rats. Moreover, we found that Cd could accelerate the metabolism of CPF in the liver when given together to the rats, which may lead to the potential antagonistic interaction between CPF and Cd. In conclusion, our results indicated that even at environmentally relevant doses, CPF and Cd could disrupt the liver metabolism. In addition, the accelerated metabolism of CPF by Cd may lead to their potential antagonistic interaction.

  20. Microbial metabolomics in open microscale platforms

    Science.gov (United States)

    Barkal, Layla J.; Theberge, Ashleigh B.; Guo, Chun-Jun; Spraker, Joe; Rappert, Lucas; Berthier, Jean; Brakke, Kenneth A.; Wang, Clay C. C.; Beebe, David J.; Keller, Nancy P.; Berthier, Erwin

    2016-01-01

    The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses to changing microenvironments. Traditional metabolomics methods are ill-equipped to probe a wide variety of environments or environmental dynamics. Here we introduce a class of microscale culture platforms to analyse chemical diversity of fungal and bacterial secondary metabolomes. By leveraging stable biphasic interfaces to integrate microculture with small molecule isolation via liquid–liquid extraction, we enable metabolomics-scale analysis using mass spectrometry. This platform facilitates exploration of culture microenvironments (including rare media typically inaccessible using established methods), unusual organic solvents for metabolite isolation and microbial mutants. Utilizing Aspergillus, a fungal genus known for its rich secondary metabolism, we characterize the effects of culture geometry and growth matrix on secondary metabolism, highlighting the potential use of microscale systems to unlock unknown or cryptic secondary metabolites for natural products discovery. Finally, we demonstrate the potential for this class of microfluidic systems to study interkingdom communication between fungi and bacteria. PMID:26842393

  1. Chemometrics Methods and Strategies in Metabolomics.

    Science.gov (United States)

    Pinto, Rui Climaco

    2017-01-01

    Chemometrics has been a fundamental discipline for the development of metabolomics, while symbiotically growing with it. From design of experiments, through data processing, to data analysis, chemometrics tools are used to design, process, visualize, explore and analyse metabolomics data.In this chapter, the most commonly used chemometrics methods for data analysis and interpretation of metabolomics experiments will be presented, with focus on multivariate analysis. These are projection-based linear methods, like principal component analysis (PCA) and orthogonal projection to latent structures (OPLS), which facilitate interpretation of the causes behind the observed sample trends, correlation with outcomes or group discrimination analysis. Validation procedures for multivariate methods will be presented and discussed.Univariate analysis is briefly discussed in the context of correlation-based linear regression methods to find associations to outcomes or in analysis of variance-based and logistic regression methods for class discrimination. These methods rely on frequentist statistics, with the determination of p-values and corresponding multiple correction procedures.Several strategies of design-analysis of metabolomics experiments will be discussed, in order to guide the reader through different setups, adopted to better address some experimental issues and to better test the scientific hypotheses.

  2. Analyzing metabolomics-based challenge test

    NARCIS (Netherlands)

    Vis, D.J.; Westerhuis, J.A.; Jacobs, D.M.; van Duynhoven, J.P.M.; Wopereis, S.; van Ommen, B.; Hendriks, M.M.W.B.; Smilde, A.K.

    2015-01-01

    Challenge tests are used to assess the resilience of human beings to perturbations by analyzing responses to detect functional abnormalities. Well known examples are allergy tests and glucose tolerance tests. Increasingly, metabolomics analysis of blood or serum samples is used to analyze the

  3. Data-processing strategies for metabolomics studies

    NARCIS (Netherlands)

    Hendriks, M.M.W.B.; Eeuwijk, van F.A.; Jellema, R.H.; Westerhuis, J.A.; Reijmers, T.H.; Hoefsloot, H.C.J.; Smilde, A.K.

    2011-01-01

    Metabolomics studies aim at a better understanding of biochemical processes by studying relations between metabolites and between metabolites and other types of information (e.g., sensory and phenotypic features). The objectives of these studies are diverse, but the types of data generated and the

  4. Metabolomics reveals energetic impairments in Daphnia magna exposed to diazinon, malathion and bisphenol-A

    Energy Technology Data Exchange (ETDEWEB)

    Nagato, Edward G.; Simpson, André J.; Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca

    2016-01-15

    changes in the metabolome. For BPA exposures, the PCA scores plot showed a significant change in metabolome at 0.1 mg/L, 1.4 mg/L and 2.1 mg/L of exposure. Individual metabolite changes from 0.7 to 2.1 mg/L of BPA exposure showed increases in amino acids such as alanine, valine, isoleucine, leucine, arginine, phenylalanine and tyrosine. These metabolite changes were correlated with decreases in glucose and lactate. This pattern of response was also seen in the highest organophosphate exposures and suggested a generalized stress response that could be related to altered energy dynamics in D. magna. Through studying increasing exposure responses, we have demonstrated the ability of metabolomics to identify discrete differences between intermediate and severe stress, and also to characterize how systemic stress is manifested in the metabolome.

  5. Metabolomics reveals energetic impairments in Daphnia magna exposed to diazinon, malathion and bisphenol-A

    International Nuclear Information System (INIS)

    Nagato, Edward G.; Simpson, André J.; Simpson, Myrna J.

    2016-01-01

    metabolome. For BPA exposures, the PCA scores plot showed a significant change in metabolome at 0.1 mg/L, 1.4 mg/L and 2.1 mg/L of exposure. Individual metabolite changes from 0.7 to 2.1 mg/L of BPA exposure showed increases in amino acids such as alanine, valine, isoleucine, leucine, arginine, phenylalanine and tyrosine. These metabolite changes were correlated with decreases in glucose and lactate. This pattern of response was also seen in the highest organophosphate exposures and suggested a generalized stress response that could be related to altered energy dynamics in D. magna. Through studying increasing exposure responses, we have demonstrated the ability of metabolomics to identify discrete differences between intermediate and severe stress, and also to characterize how systemic stress is manifested in the metabolome.

  6. Characterization and Discrimination of Ancient Grains: A Metabolomics Approach

    Directory of Open Access Journals (Sweden)

    Laura Righetti

    2016-07-01

    Full Text Available Hulled, or ancient, wheats were the earliest domesticated wheats by mankind and the ancestors of current wheats. Their cultivation drastically decreased during the 1960s; however, the increasing demand for a healthy and equilibrated diet led to rediscovering these grains. Our aim was to use a non-targeted metabolomic approach to discriminate and characterize similarities and differences between ancient Triticum varieties. For this purpose, 77 hulled wheat samples from three different varieties were collected: Garfagnana T. turgidum var. dicoccum L. (emmer, ID331 T. monococcum L. (einkorn and Rouquin T. spelta L. (spelt. The ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-QTOF metabolomics approach highlighted a pronounced sample clustering according to the wheat variety, with an excellent predictability (Q2, for all the models built. Fifteen metabolites were tentatively identified based on accurate masses, isotopic pattern, and product ion spectra. Among these, alkylresorcinols (ARs were found to be significantly higher in spelt and emmer, showing different homologue composition. Furthermore, phosphatidylcholines (PC and lysophosphatidylcholines (lysoPC levels were higher in einkorn variety. The results obtained in this study confirmed the importance of ARs as markers to distinguish between Triticum species and revealed their values as cultivar markers, being not affected by the environmental influences.

  7. Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination

    Directory of Open Access Journals (Sweden)

    Takao Itoi

    2017-04-01

    Full Text Available This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC from malignant diseases, such as biliary tract cancer (BTC, intraductal papillary mucinous carcinoma (IPMC, and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41 of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140. Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test. Four multiple logistic regression models (MLR were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC of 0.970 (95% confidential interval (CI, 0.946–0.994, p < 0.0001. Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020 with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, pancreatic cancer-associated antigen (DUPAN2 and s-pancreas-1 antigen (SPAN1. Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

  8. Obesity and psychotic disorders: uncovering common mechanisms through metabolomics

    Directory of Open Access Journals (Sweden)

    Matej Orešič

    2012-09-01

    Full Text Available Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. This review covers how recent metabolomic studies have advanced biomarker discovery and the elucidation of mechanisms underlying obesity and its co-morbidities, with a specific focus on metabolic syndrome and psychotic disorders. The importance of identifying metabolic markers of disease-associated intermediate phenotypes – traits modulated but not encoded by the DNA sequence – is emphasized. Such markers would be applicable as diagnostic tools in a personalized healthcare setting and might also open up novel therapeutic avenues.

  9. Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts

    Science.gov (United States)

    Macintyre, Lynsey; Zhang, Tong; Viegelmann, Christina; Juarez Martinez, Ignacio; Cheng, Cheng; Dowdells, Catherine; Abdelmohsen, Usama Ramadan; Gernert, Christine; Hentschel, Ute; Edrada-Ebel, RuAngelie

    2014-01-01

    Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening. PMID:24905482

  10. Oral health: equity and social determinants

    DEFF Research Database (Denmark)

    Kwan, Stella; Petersen, Poul Erik

    2010-01-01

    This book chapter discusses the social determinants of oral health, and identifies interventions that have been, or can be, used in addressing oral health inequities (e.g. oral health promotion, education programmes, improving access to oral health care).......This book chapter discusses the social determinants of oral health, and identifies interventions that have been, or can be, used in addressing oral health inequities (e.g. oral health promotion, education programmes, improving access to oral health care)....

  11. Development of chemical isotope labeling liquid chromatography mass spectrometry for silkworm hemolymph metabolomics

    International Nuclear Information System (INIS)

    Shen, Weifeng; Han, Wei; Li, Yunong; Meng, Zhiqi; Cai, Leiming; Li, Liang

    2016-01-01

    Silkworm (Bombyx mori) is a very useful target insect for evaluation of endocrine disruptor chemicals (EDCs) due to mature breeding techniques, complete endocrine system and broad basic knowledge on developmental biology. Comparative metabolomics of silkworms with and without EDC exposure offers another dimension of studying EDCs. In this work, we report a workflow on metabolomic profiling of silkworm hemolymph based on high-performance chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) and demonstrate its application in studying the metabolic changes associated with the pesticide dichlorodiphenyltrichloroethane (DDT) exposure in silkworm. Hemolymph samples were taken from mature silkworms after growing on diet that contained DDT at four different concentrations (1, 0.1, 0.01, 0.001 ppm) as well as on diet without DDT as controls. They were subjected to differential 12 C-/ 13 C-dansyl labeling of the amine/phenol submetabolome, LC-UV quantification of the total amount of labeled metabolites for sample normalization, and LC-MS detection and relative quantification of individual metabolites in comparative samples. The total concentration of labeled metabolites did not show any significant change between four DDT-treatment groups and one control group. Multivariate statistical analysis of the metabolome data set showed that there was a distinct metabolomic separation between the five groups. Out of the 2044 detected peak pairs, 338 and 1471 metabolites have been putatively identified against the HMDB database and the EML library, respectively. 65 metabolites were identified by the dansyl library searching based on the accurate mass and retention time. Among the 65 identified metabolites, 33 positive metabolites had changes of greater than 1.20-fold or less than 0.83-fold in one or more groups with p-value of smaller than 0.05. Several useful biomarkers including serine, methionine, tryptophan, asymmetric dimethylarginine, N

  12. Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics.

    Science.gov (United States)

    Mu, Chunlong; Yang, Yuxiang; Yu, Kaifan; Yu, Miao; Zhang, Chuanjian; Su, Yong; Zhu, Weiyun

    2017-04-01

    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 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 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 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.

  13. Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules.

    Science.gov (United States)

    Pannkuk, Evan L; Fornace, Albert J; Laiakis, Evagelia C

    2017-10-01

    Exposure of the general population to ionizing radiation has increased in the past decades, primarily due to long distance travel and medical procedures. On the other hand, accidental exposures, nuclear accidents, and elevated threats of terrorism with the potential detonation of a radiological dispersal device or improvised nuclear device in a major city, all have led to increased needs for rapid biodosimetry and assessment of exposure to different radiation qualities and scenarios. Metabolomics, the qualitative and quantitative assessment of small molecules in a given biological specimen, has emerged as a promising technology to allow for rapid determination of an individual's exposure level and metabolic phenotype. Advancements in mass spectrometry techniques have led to untargeted (discovery phase, global assessment) and targeted (quantitative phase) methods not only to identify biomarkers of radiation exposure, but also to assess general perturbations of metabolism with potential long-term consequences, such as cancer, cardiovascular, and pulmonary disease. Metabolomics of radiation exposure has provided a highly informative snapshot of metabolic dysregulation. Biomarkers in easily accessible biofluids and biospecimens (urine, blood, saliva, sebum, fecal material) from mouse, rat, and minipig models, to non-human primates and humans have provided the basis for determination of a radiation signature to assess the need for medical intervention. Here we provide a comprehensive description of the current status of radiation metabolomic studies for the purpose of rapid high-throughput radiation biodosimetry in easily accessible biofluids and discuss future directions of radiation metabolomics research.

  14. Oral Health

    Science.gov (United States)

    ... section Home A-Z Health Topics Oral health Oral health > A-Z Health Topics Oral health (PDF, 154 ... To receive Publications email updates Enter email Submit Oral health Women have unique oral health concerns. Changing hormone ...

  15. mzGroupAnalyzer--predicting pathways and novel chemical structures from untargeted high-throughput metabolomics data.

    Science.gov (United States)

    Doerfler, Hannes; Sun, Xiaoliang; Wang, Lei; Engelmeier, Doris; Lyon, David; Weckwerth, Wolfram

    2014-01-01

    The metabolome is a highly dynamic entity and the final readout of the genotype x environment x phenotype (GxExP) relationship of an organism. Monitoring metabolite dynamics over time thus theoretically encrypts the whole range of possible chemical and biochemical transformations of small molecules involved in metabolism. The bottleneck is, however, the sheer number of unidentified structures in these samples. This represents the next challenge for metabolomics technology and is comparable with genome sequencing 30 years ago. At the same time it is impossible to handle the amount of data involved in a metabolomics analysis manually. Algorithms are therefore imperative to allow for automated m/z feature extraction and subsequent structure or pathway assignment. Here we provide an automated pathway inference strategy comprising measurements of metabolome time series using LC- MS with high resolution and high mass accuracy. An algorithm was developed, called mzGroupAnalyzer, to automatically explore the metabolome for the detection of metabolite transformations caused by biochemical or chemical modifications. Pathways are extracted directly from the data and putative novel structures can be identified. The detected m/z features can be mapped on a van Krevelen diagram according to their H/C and O/C ratios for pattern recognition and to visualize oxidative processes and biochemical transformations. This method was applied to Arabidopsis thaliana treated simultaneously with cold and high light. Due to a protective antioxidant response the plants turn from green to purple color via the accumulation of flavonoid structures. The detection of potential biochemical pathways resulted in 15 putatively new compounds involved in the flavonoid-pathway. These compounds were further validated by product ion spectra from the same data. The mzGroupAnalyzer is implemented in the graphical user interface (GUI) of the metabolomics toolbox COVAIN (Sun & Weckwerth, 2012, Metabolomics 8: 81

  16. mzGroupAnalyzer--predicting pathways and novel chemical structures from untargeted high-throughput metabolomics data.

    Directory of Open Access Journals (Sweden)

    Hannes Doerfler

    Full Text Available The metabolome is a highly dynamic entity and the final readout of the genotype x environment x phenotype (GxExP relationship of an organism. Monitoring metabolite dynamics over time thus theoretically encrypts the whole range of possible chemical and biochemical transformations of small molecules involved in metabolism. The bottleneck is, however, the sheer number of unidentified structures in these samples. This represents the next challenge for metabolomics technology and is comparable with genome sequencing 30 years ago. At the same time it is impossible to handle the amount of data involved in a metabolomics analysis manually. Algorithms are therefore imperative to allow for automated m/z feature extraction and subsequent structure or pathway assignment. Here we provide an automated pathway inference strategy comprising measurements of metabolome time series using LC- MS with high resolution and high mass accuracy. An algorithm was developed, called mzGroupAnalyzer, to automatically explore the metabolome for the detection of metabolite transformations caused by biochemical or chemical modifications. Pathways are extracted directly from the data and putative novel structures can be identified. The detected m/z features can be mapped on a van Krevelen diagram according to their H/C and O/C ratios for pattern recognition and to visualize oxidative processes and biochemical transformations. This method was applied to Arabidopsis thaliana treated simultaneously with cold and high light. Due to a protective antioxidant response the plants turn from green to purple color via the accumulation of flavonoid structures. The detection of potential biochemical pathways resulted in 15 putatively new compounds involved in the flavonoid-pathway. These compounds were further validated by product ion spectra from the same data. The mzGroupAnalyzer is implemented in the graphical user interface (GUI of the metabolomics toolbox COVAIN (Sun & Weckwerth, 2012

  17. Metabolic changes associated with papillary thyroid carcinoma: A nuclear magnetic resonance-based metabolomics study.

    Science.gov (United States)

    Li, Yanyun; Chen, Minjian; Liu, Cuiping; Xia, Yankai; Xu, Bo; Hu, Yanhui; Chen, Ting; Shen, Meiping; Tang, Wei

    2018-05-01

    Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients. The results were further annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG), and Human Metabolome Database, and then were analyzed using modules of pathway analysis and enrichment analysis of MetaboAnalyst 3.0. Based on the analytical techniques, we established the models of principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS‑DA) which could discriminate PTC from normal thyroid tissue, and found 15 robust differentiated metabolites from two OPLS-DA models. We identified 8 KEGG pathways and 3 pathways of small molecular pathway database which were significantly related to PTC by using pathway analysis and enrichment analysis, respectively, through which we identified metabolisms related to PTC including branched chain amino acid metabolism (leucine and valine), other amino acid metabolism (glycine and taurine), glycolysis (lactate), tricarboxylic acid cycle (citrate), choline metabolism (choline, ethanolamine and glycerolphosphocholine) and lipid metabolism (very-low‑density lipoprotein and low-density lipoprotein). In conclusion, the PTC was characterized with increased glycolysis and inhibited tricarboxylic acid cycle, increased oncogenic amino acids as well as abnormal choline and lipid metabolism. The findings in this study provide new

  18. Establishment of Protocols for Global Metabolomics by LC-MS for Biomarker Discovery.

    Directory of Open Access Journals (Sweden)

    Daisuke Saigusa

    Full Text Available Metabolomics is a promising avenue for biomarker discovery. Although the quality of metabolomic analyses, especially global metabolomics (G-Met using mass spectrometry (MS, largely depends on the instrumentation, potential bottlenecks still exist at several basic levels in the metabolomics workflow. Therefore, we established a precise protocol initially for the G-Met analyses of human blood plasma to overcome some these difficulties. In our protocol, samples are deproteinized in a 96-well plate using an automated liquid-handling system, and conducted either using a UHPLC-QTOF/MS system equipped with a reverse phase column or a LC-FTMS system equipped with a normal phase column. A normalization protocol of G-Met data was also developed to compensate for intra- and inter-batch differences, and the variations were significantly reduced along with our normalization, especially for the UHPLC-QTOF/MS data with a C18 reverse-phase column for positive ions. Secondly, we examined the changes in metabolomic profiles caused by the storage of EDTA-blood specimens to identify quality markers for the evaluation of the specimens' pre-analytical conditions. Forty quality markers, including lysophospholipids, dipeptides, fatty acids, succinic acid, amino acids, glucose, and uric acid were identified by G-Met for the evaluation of plasma sample quality and established the equation of calculating the quality score. We applied our quality markers to a small-scale study to evaluate the quality of clinical samples. The G-Met protocols and quality markers established here should prove useful for the discovery and development of biomarkers for a wider range of diseases.

  19. Impact of a western diet on the ovarian and serum metabolome.

    Science.gov (United States)

    Dhungana, Suraj; Carlson, James E; Pathmasiri, Wimal; McRitchie, Susan; Davis, Matt; Sumner, Susan; Appt, Susan E

    2016-10-01

    The objective of this investigation was to determine differences in the profiles of endogenous metabolites (metabolomics) among ovaries and serum derived from Old World nonhuman primates fed prudent or Western diets. A retrospective, observational study was done using archived ovarian tissue and serum from midlife cynomolgus monkeys (Macaca fasicularis). Targeted and broad spectrum metabolomics analysis was used to compare ovarian tissue and serum from monkeys that had been exposed to a prudent diet or a Western diet. Monkeys in the prudent diet group (n=13) were research naïve and had been exposed only to a commercial monkey chow diet (low in cholesterol and saturated fats, high in complex carbohydrates). Western diet monkeys (n=8) had consumed a diet that was high in cholesterol, saturated animal fats and soluble carbohydrates for 2 years prior to ovarian tissue and serum collection. Metabolomic analyses were done on extracts of homogenized ovary tissue samples, and extracts of serum. Targeted analysis was conducted using the Biocrates p180 kit and broad spectrum analysis was conducted using UPLC-TOF-MS, resulting in the detection of 3500 compound ions. Using metabolomics methods, which capture thousands of signals for metabolites, 64 metabolites were identified in serum and 47 metabolites were identified in ovarian tissue that differed by diet. Quantitative targeted analysis revealed 13 amino acids, 6 acrylcarnitines, and 2 biogenic amines that were significantly (pdiet groups for serum extracts, and similar results were observed for the ovary extracts. These data demonstrate that dietary exposure had a significant impact on the serum and ovarian metabolome, and demonstrated perturbation in carnitine, lipids/fatty acid, and amino acid metabolic pathways. Published by Elsevier Ireland Ltd.

  20. Quantitative metabolomics based on gas chromatography mass spectrometry: Status and perspectives

    NARCIS (Netherlands)

    Koek, M.M.; Jellema, R.H.; Greef, J. van der; Tas, A.C.; Hankemeier, T.

    2011-01-01

    Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues (the metabolome). By analyzing differences between metabolomes using biostatistics (multivariate data analysis; pattern recognition), metabolites

  1. The food-gut human axis: the effects of diet on gut microbiota and metabolome.

    Science.gov (United States)

    De Angelis, Maria; Garruti, Gabriella; Minervini, Fabio; Bonfrate, Leonilde; Portincasa, Piero; Gobbetti, Marco

    2017-04-27

    Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influences the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Salivary and fecal microbiota and metabolome of celiac children under gluten-free diet.

    Science.gov (United States)

    De Angelis, Maria; Vannini, Lucia; Di Cagno, Raffaella; Cavallo, Noemi; Minervini, Fabio; Francavilla, Ruggiero; Ercolini, Danilo; Gobbetti, Marco

    2016-12-19

    Celiac disease (CD) is an inflammatory autoimmune disorder resulting from the combination of genetic predisposition and gluten ingestion. A life-long gluten free diet (GFD) is the only therapeutic approach. Dysbiosis, which can precede the CD pathogenesis and/or persist when subjects are on GFD, is reviewed and discussed. Salivary microbiota and metabolome differed between healthy and celiac children treated under GFD (T-CD) for at least two years. The type of GFD (African- vs Italian-style) modified the microbiota and metabolome of Saharawi T-CD children. Different studies showed bacterial dysbiosis at duodenal and/or fecal level of patients with active untreated CD (U-CD) and T-CD compared to healthy subjects. The ratio of protective anti-inflammatory bacteria such as Lactobacillus-Bifidobacterium to potentially harmful Bacteroides-Enterobacteriaceae was the lowest in U-CD and T-CD children. In agreement with dysbiosis, serum, fecal and urinary metabolome from U-CD and T-CD patients showed altered levels of free amino acids and volatile organic compounds. However, consensus across studies defining specific bacteria and metabolites in U-CD or T-CD patients is still lacking. Future research efforts are required to determine the relationships between CD and oral and intestinal microbiotas to improve the composition of GFD for restoring the gut dysbiosis as a preventative or therapeutic approach for CD. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Discovery of biomarkers for oxidative stress based on cellular metabolomics.

    Science.gov (United States)

    Wang, Ningli; Wei, Jianteng; Liu, Yewei; Pei, Dong; Hu, Qingping; Wang, Yu; Di, Duolong

    2016-07-01

    Oxidative stress has a close relationship with various pathologic physiology phenomena and the potential biomarkers of oxidative stress may provide evidence for clinical diagnosis or disease prevention. Metabolomics was employed to identify the potential biomarkers of oxidative stress. High-performance liquid chromatography-diode array detector, mass spectrometry and partial least squares discriminate analysis were used in this study. The 10, 15 and 13 metabolites were considered to discriminate the model group, vitamin E-treated group and l-glutathione-treated group, respectively. Some of them have been identified, namely, malic acid, vitamin C, reduced glutathione and tryptophan. Identification of other potential biomarkers should be conducted and their physiological significance also needs to be elaborated.

  4. An oral keratinocyte life cycle model identifies novel host genome regulation by human papillomavirus 16 relevant to HPV positive head and neck cancer.

    Science.gov (United States)

    Evans, Michael R; James, Claire D; Loughran, Oonagh; Nulton, Tara J; Wang, Xu; Bristol, Molly L; Windle, Brad; Morgan, Iain M

    2017-10-10

    Many aspects of the HPV life cycle have been characterized in cervical cell lines (W12, CIN612) and in HPV immortalized primary foreskin keratinocytes. There is now an epidemic of HPV positive oropharyngeal cancers (HPV16 is responsible for 80-90% of these); therefore increased understanding of the HPV16 life cycle in oral keratinocytes is a priority. To date there have been limited reports characterizing the HPV16 life cycle in oral keratinocytes. Using TERT immortalized "normal" oral keratinocytes (NOKs) we generated clonal cell lines maintaining the HPV16 genome as an episome, NOKs+HPV16. Organotypic raft cultures demonstrated appropriate expression of differentiation markers, E1^E4 and E2 expression along with amplification of the viral genome in the upper layers of the epithelium. Using this unique system RNA-seq analysis revealed extensive gene regulation of the host genome by HPV16; many of the changes have not been observed for HPV16 before. The RNA-seq data was validated on a key set of anti-viral innate immune response genes repressed by HPV16 in NOKs+HPV16. We show that the behavior of these NOKs+HPV16 lines is identical to HPV16 immortalized human tonsil keratinocytes with regards innate gene regulation. Finally, using The Cancer Genome Atlas (TCGA) data we examined gene expression patterns from HPV positive and negative head and neck cancers and demonstrate this innate immune gene signature set is also downregulated in HPV positive cancers versus negative. Our system provides a model for understanding HPV16 transcriptional regulation of oral keratinocytes that is directly relevant to HPV positive head and neck cancer.

  5. Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer

    DEFF Research Database (Denmark)

    Reis, Patricia P; Rogatto, Silvia R; Kowalski, Luiz P

    2002-01-01

    Quantitative real time PCR was performed on genomic DNA from 40 primary oral carcinomas and the normal adjacent tissues. The target genes ECGFB, DIA1, BIK, and PDGFB and the microsatellite markers D22S274 and D22S277, mapped on 22q13, were selected according to our previous loss of heterozygosity.......0018) for patients with DIA1 gene loss. Relative copy number losses detected in these sequences may be related to disease progression and a worse prognosis in patients with oral cancer....... System (PE Applied Biosystems). Losses in the sequences D22S274 (22q13.31) and in the DIA1 (22q13.2-13.31) gene were detected in 10 out of 40 cases (25%) each. Statistically significant correlations were observed for patients with relative copy number loss of the marker D22S274 and stages T3-T4......Quantitative real time PCR was performed on genomic DNA from 40 primary oral carcinomas and the normal adjacent tissues. The target genes ECGFB, DIA1, BIK, and PDGFB and the microsatellite markers D22S274 and D22S277, mapped on 22q13, were selected according to our previous loss of heterozygosity...

  6. Metabolomics reveals distinct neurochemical profiles associated with stress resilience

    Directory of Open Access Journals (Sweden)

    Brooke N. Dulka

    2017-12-01

    Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings

  7. Binary similarity measures for fingerprint analysis of qualitative metabolomic profiles.

    Science.gov (United States)

    Rácz, Anita; Andrić, Filip; Bajusz, Dávid; Héberger, Károly

    2018-01-01

    Contemporary metabolomic fingerprinting is based on multiple spectrometric and chromatographic signals, used either alone or combined with structural and chemical information of metabolic markers at the qualitative and semiquantitative level. However, signal shifting, convolution, and matrix effects may compromise metabolomic patterns. Recent increase in the use of qualitative metabolomic data, described by the presence (1) or absence (0) of particular metabolites, demonstrates great potential in the field of metabolomic profiling and fingerprint analysis. The aim of this study is a comprehensive evaluation of binary similarity measures for the elucidation of patterns among samples of different botanical origin and various metabolomic profiles. Nine qualitative metabolomic data sets covering a wide range of natural products and metabolomic profiles were applied to assess 44 binary similarity measures for the fingerprinting of plant extracts and natural products. The measures were analyzed by the novel sum of ranking differences method (SRD), searching for the most promising candidates. Baroni-Urbani-Buser (BUB) and Hawkins-Dotson (HD) similarity coefficients were selected as the best measures by SRD and analysis of variance (ANOVA), while Dice (Di1), Yule, Russel-Rao, and Consonni-Todeschini 3 ranked the worst. ANOVA revealed that concordantly and intermediately symmetric similarity coefficients are better candidates for metabolomic fingerprinting than the asymmetric and correlation based ones. The fingerprint analysis based on the BUB and HD coefficients and qualitative metabolomic data performed equally well as the quantitative metabolomic profile analysis. Fingerprint analysis based on the qualitative metabolomic profiles and binary similarity measures proved to be a reliable way in finding the same/similar patterns in metabolomic data as that extracted from quantitative data.

  8. Metabolomics-Driven Nutraceutical Evaluation of Diverse Green Tea Cultivars

    OpenAIRE

    Fujimura, Yoshinori; Kurihara, Kana; Ida, Megumi; Kosaka, Reia; Miura, Daisuke; Wariishi, Hiroyuki; Maeda-Yamamoto, Mari; Nesumi, Atsushi; Saito, Takeshi; Kanda, Tomomasa; Yamada, Koji; Tachibana, Hirofumi

    2011-01-01

    BACKGROUND: Green tea has various health promotion effects. Although there are numerous tea cultivars, little is known about the differences in their nutraceutical properties. Metabolic profiling techniques can provide information on the relationship between the metabolome and factors such as phenotype or quality. Here, we performed metabolomic analyses to explore the relationship between the metabolome and health-promoting attributes (bioactivity) of diverse Japanese green tea cultivars. MET...

  9. Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization.

    Science.gov (United States)

    Bellver, José; De Los Santos, María J; Alamá, Pilar; Castelló, Damià; Privitera, Laura; Galliano, Daniela; Labarta, Elena; Vidal, Carmen; Pellicer, Antonio; Domínguez, Francisco

    2015-06-01

    To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF). Prospective cohort analysis. IVF clinic. Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12). Fifty μl of SCM collected from two day-3 embryos of each cohort. Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos. The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS. The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present. NCT01448863. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

    Science.gov (United States)

    Ktsoyan, Zhanna A.; Beloborodova, Natalia V.; Sedrakyan, Anahit M.; Osipov, George A.; Khachatryan, Zaruhi A.; Manukyan, Gayane P.; Arakelova, Karine A.; Hovhannisyan, Alvard I.; Arakelyan, Arsen A.; Ghazaryan, Karine A.; Zakaryan, Magdalina K.; Aminov, Rustam I.

    2013-01-01

    In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome. PMID:23373011

  11. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

    Directory of Open Access Journals (Sweden)

    Zhanna eKtsoyan

    2013-01-01

    Full Text Available In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever, the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

  12. Analysis of metabolomic data: tools, current strategies and future challenges for omics data integration.

    Science.gov (United States)

    Cambiaghi, Alice; Ferrario, Manuela; Masseroli, Marco

    2017-05-01

    Metabolomics is a rapidly growing field consisting of the analysis of a large number of metabolites at a system scale. The two major goals of metabolomics are the identification of the metabolites characterizing each organism state and the measurement of their dynamics under different situations (e.g. pathological conditions, environmental factors). Knowledge about metabolites is crucial for the understanding of most cellular phenomena, but this information alone is not sufficient to gain a comprehensive view of all the biological processes involved. Integrated approaches combining metabolomics with transcriptomics and proteomics are thus required to obtain much deeper insights than any of these techniques alone. Although this information is available, multilevel integration of different 'omics' data is still a challenge. The handling, processing, analysis and integration of these data require specialized mathematical, statistical and bioinformatics tools, and several technical problems hampering a rapid progress in the field exist. Here, we review four main tools for number of users or provided features (MetaCoreTM, MetaboAnalyst, InCroMAP and 3Omics) out of the several available for metabolomic data analysis and integration with other 'omics' data, highlighting their strong and weak aspects; a number of related issues affecting data analysis and integration are also identified and discussed. Overall, we provide an objective description of how some of the main currently available software packages work, which may help the experimental practitioner in the choice of a robust pipeline for metabolomic data analysis and integration. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. NMR-based metabolomics in human disease diagnosis: Applications, limitations, and recommendations

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2013-04-03

    Metabolomics is a dynamic and emerging research field, similar to proteomics, transcriptomics and genomics in affording global understanding of biological systems. It is particularly useful in functional genomic studies in which metabolism is thought to be perturbed. Metabolomics provides a snapshot of the metabolic dynamics that reflect the response of living systems to both pathophysiological stimuli and/or genetic modification. Because this approach makes possible the examination of interactions between an organism and its diet or environment, it is particularly useful for identifying biomarkers of disease processes that involve the environment. For example, the interaction of a high fat diet with cardiovascular disease can be studied via such a metabolomics approach by modeling the interaction between genes and diet. The high reproducibility of NMR-based techniques gives this method a number of advantages over other analytical techniques in large-scale and long-term metabolomic studies, such as epidemiological studies. This approach has been used to study a wide range of diseases, through the examination of biofluids, including blood plasma/serum, urine, blister fluid, saliva and semen, as well as tissue extracts and intact tissue biopsies. However, complicating the use of NMR spectroscopy in biomarker discovery is the fact that numerous variables can effect metabolic composition including, fasting, stress, drug administration, diet, gender, age, physical activity, life style and the subject\\'s health condition. To minimize the influence of these variations in the datasets, all experimental conditions including sample collection, storage, preparation as well as NMR spectroscopic parameters and data analysis should be optimized carefully and conducted in an identical manner as described by the local standard operating protocol. This review highlights the potential applications of NMR-based metabolomics studies and gives some recommendations to improve sample

  14. Advances in metabolome information retrieval: turning chemistry into biology. Part I: analytical chemistry of the metabolome.

    Science.gov (United States)

    Tebani, Abdellah; Afonso, Carlos; Bekri, Soumeya

    2017-08-24

    Metabolites are small molecules produced by enzymatic reactions in a given organism. Metabolomics or metabolic phenotyping is a well-established omics aimed at comprehensively assessing metabolites in biological systems. These comprehensive analyses use analytical platforms, mainly nuclear magnetic resonance spectroscopy and mass spectrometry, along with associated separation methods to gather qualitative and quantitative data. Metabolomics holistically evaluates biological systems in an unbiased, data-driven approach that may ultimately support generation of hypotheses. The approach inherently allows the molecular characterization of a biological sample with regard to both internal (genetics) and environmental (exosome, microbiome) influences. Metabolomics workflows are based on whether the investigator knows a priori what kind of metabolites to assess. Thus, a targeted metabolomics approach is defined as a quantitative analysis (absolute concentrations are determined) or a semiquantitative analysis (relative intensities are determined) of a set of metabolites that are possibly linked to common chemical classes or a selected metabolic pathway. An untargeted metabolomics approach is a semiquantitative analysis of the largest possible number of metabolites contained in a biological sample. This is part I of a review intending to give an overview of the state of the art of major metabolic phenotyping technologies. Furthermore, their inherent analytical advantages and limits regarding experimental design, sample handling, standardization and workflow challenges are discussed.

  15. Human gut microbes impact host serum metabolome and insulin sensitivity

    DEFF Research Database (Denmark)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn

    2016-01-01

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individ......Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin...

  16. Metabolomic analysis of three Mollicute species.

    Directory of Open Access Journals (Sweden)

    Anna A Vanyushkina

    Full Text Available We present a systematic study of three bacterial species that belong to the class Mollicutes, the smallest and simplest bacteria, Spiroplasma melliferum, Mycoplasma gallisepticum, and Acholeplasma laidlawii. To understand the difference in the basic principles of metabolism regulation and adaptation to environmental conditions in the three species, we analyzed the metabolome of these bacteria. Metabolic pathways were reconstructed using the proteogenomic annotation data provided by our lab. The results of metabolome, proteome and genome profiling suggest a fundamental difference in the adaptation of the three closely related Mollicute species to stress conditions. As the transaldolase is not annotated in Mollicutes, we propose variants of the pentose phosphate pathway catalyzed by annotated enzymes for three species. For metabolite detection we employed high performance liquid chromatography coupled with mass spectrometry. We used liquid chromatography method - hydrophilic interaction chromatography with silica column - as it effectively separates highly polar cellular metabolites prior to their detection by mass spectrometer.

  17. Mapping the variation of the carrot metabolome using 1H NMR spectroscopy and consensus PCA.

    Science.gov (United States)

    Clausen, Morten Rahr; Edelenbos, Merete; Bertram, Hanne Christine

    2014-05-14

    Genetic variation is the most influential factor for carrot (Daucus carota L.) composition. However, difference in metabolite content between carrot varieties has not been described by NMR, although primary metabolites are important for human health and sensory properties. The aim of the present study was to investigate the effect of genotype on carrot metabolite composition using a (1)H NMR-based metabolomics approach. After extraction using aqueous and organic solvents, 25 hydrophilic metabolites, β-carotene, sterols, triacylglycerols, and phospholipids were detected. Multiblock PCA showed that three principal components could be identified for classification of the five carrot varieties using different spectroscopic regions and the results of the two solvent extraction methods as blocks. The varieties were characterized by differences in carbohydrate, amino acid, nucleotide, fatty acid, sterol, and β-carotene contents. (1)H NMR spectroscopy coupled with multiblock data analysis was an efficient and useful tool to map the carrot metabolome and identify genetic differences between varieties.

  18. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    DEFF Research Database (Denmark)

    Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W

    2015-01-01

    PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems...... protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were...

  19. Data fusion in metabolomic cancer diagnostics

    DEFF Research Database (Denmark)

    Bro, Rasmus; Nielsen, Hans Jørgen; Savorani, Francesco

    2013-01-01

    We have recently shown that fluorescence spectroscopy of plasma samples has promising abilities regarding early detection of colorectal cancer. In the present paper, these results were further developed by combining fluorescence with the biomarkers, CEA and TIMP-1 and traditional metabolomic...... measurements in the form of (1)H NMR spectroscopy. The results indicate that using an extensive profile established by combining such measurements together with the biomarkers is better than using single markers....

  20. Stable isotope- and mass spectrometry-based metabolomics as tools in drug metabolism: a study expanding tempol pharmacology.

    Science.gov (United States)

    Li, Fei; Pang, Xiaoyan; Krausz, Kristopher W; Jiang, Changtao; Chen, Chi; Cook, John A; Krishna, Murali C; Mitchell, James B; Gonzalez, Frank J; Patterson, Andrew D

    2013-03-01

    The application of mass spectrometry-based metabolomics in the field of drug metabolism has yielded important insights not only into the metabolic routes of drugs but has provided unbiased, global perspectives of the endogenous metabolome that can be useful for identifying biomarkers associated with mechanism of action, efficacy, and toxicity. In this report, a stable isotope- and mass spectrometry-based metabolomics approach that captures both drug metabolism and changes in the endogenous metabolome in a single experiment is described. Here the antioxidant drug tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) was chosen because its mechanism of action is not completely understood and its metabolic fate has not been studied extensively. Furthermore, its small size (MW = 172.2) and chemical composition (C(9)H(18)NO(2)) make it challenging to distinguish from endogenous metabolites. In this study, mice were dosed with tempol or deuterated tempol (C(9)D(17)HNO(2)) and their urine was profiled using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Principal component analysis of the urinary metabolomics data generated a Y-shaped scatter plot containing drug metabolites (protonated and deuterated) that were clearly distinct from the endogenous metabolites. Ten tempol drug metabolites, including eight novel metabolites, were identified. Phase II metabolism was the major metabolic pathway of tempol in vivo, including glucuronidation and glucosidation. Urinary endogenous metabolites significantly elevated by tempol treatment included 2,8-dihydroxyquinoline (8.0-fold, P tempol treatment including pantothenic acid (1.3-fold, P < 0.05) and isobutrylcarnitine (5.3-fold, P < 0.01). This study underscores the power of a stable isotope- and mass spectrometry-based metabolomics in expanding the view of drug pharmacology.

  1. Metabolomics tools for the synthetic biology of natural products.

    Science.gov (United States)

    Hollywood, Katherine A; Schmidt, Kamila; Takano, Eriko; Breitling, Rainer

    2018-03-19

    Metabolomics plays an increasingly central role within the Design-Build-Test cycle of synthetic biology, in particular in applications targeting the discovery, diversification and optimised production of a wide range of natural products. For example, improved methods for the online monitoring of chemical reactions accelerate data generation to be compatible with the rapid iterations and increasing library sizes of automated synthetic biology pipelines. Combinations of label-free metabolic profiling and 13 C-based flux analysis lead to increased resolution in the identification of metabolic bottlenecks affecting product yield in engineered microbes. And molecular networking strategies drastically increase our ability to identify and characterise novel chemically complex biomolecules of interest in a diverse range of samples. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Global open data management in metabolomics.

    Science.gov (United States)

    Haug, Kenneth; Salek, Reza M; Steinbeck, Christoph

    2017-02-01

    Chemical Biology employs chemical synthesis, analytical chemistry and other tools to study biological systems. Recent advances in both molecular biology such as next generation sequencing (NGS) have led to unprecedented insights towards the evolution of organisms' biochemical repertoires. Because of the specific data sharing culture in Genomics, genomes from all kingdoms of life become readily available for further analysis by other researchers. While the genome expresses the potential of an organism to adapt to external influences, the Metabolome presents a molecular phenotype that allows us to asses the external influences under which an organism exists and develops in a dynamic way. Steady advancements in instrumentation towards high-throughput and highresolution methods have led to a revival of analytical chemistry methods for the measurement and analysis of the metabolome of organisms. This steady growth of metabolomics as a field is leading to a similar accumulation of big data across laboratories worldwide as can be observed in all of the other omics areas. This calls for the development of methods and technologies for handling and dealing with such large datasets, for efficiently distributing them and for enabling re-analysis. Here we describe the recently emerging ecosystem of global open-access databases and data exchange efforts between them, as well as the foundations and obstacles that enable or prevent the data sharing and reanalysis of this data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. An Ultrahigh-Performance Liquid Chromatography-Time-of-Flight Mass Spectrometry Metabolomic Approach to Studying the Impact of Moderate Red-Wine Consumption on Urinary Metabolome.

    Science.gov (United States)

    Esteban-Fernández, Adelaida; Ibañez, Clara; Simó, Carolina; Bartolomé, Begoña; Moreno-Arribas, M Victoria

    2018-04-06

    Moderate red-wine consumption has been widely described to exert several benefits in human health. This is mainly due to its unique content of bioactive polyphenols, which suffer several modifications along their pass through the digestive system, including microbial transformation in the colon and phase-II metabolism, until they are finally excreted in urine and feces. To determine the impact of moderate wine consumption in the overall urinary metabolome of healthy volunteers ( n = 41), samples from a red-wine interventional study (250 mL/day, 28 days) were investigated. Urine (24 h) was collected before and after intervention and analyzed by an untargeted ultrahigh-performance liquid chromatography-time-of-flight mass spectrometry metabolomics approach. 94 compounds linked to wine consumption, including specific wine components (tartaric acid), microbial-derived phenolic metabolites (5-(dihydroxyphenyl)-γ-valerolactones and 4-hydroxyl-5-(phenyl)-valeric acids), and endogenous compounds were identified. Also, some relationships between parallel fecal and urinary metabolomes are discussed.

  4. Impact of a cafeteria diet and daily physical training on the rat serum metabolome.

    Directory of Open Access Journals (Sweden)

    Susana Suárez-García

    Full Text Available Regular physical activity and healthy dietary patterns are commonly recommended for the prevention and treatment of metabolic syndrome (MetS, which is diagnosed at an alarmingly increasing rate, especially among adolescents. Nevertheless, little is known regarding the relevance of physical exercise on the modulation of the metabolome in healthy people and those with MetS. We have previously shown that treadmill exercise ameliorated different symptoms of MetS. The aim of this study was to investigate the impact of a MetS-inducing diet and different intensities of aerobic training on the overall serum metabolome of adolescent rats. For 8 weeks, young rats were fed either standard chow (ST or cafeteria diet (CAF and were subjected to a daily program of training on a treadmill at different speeds. Non-targeted metabolomics was used to identify changes in circulating metabolites, and a combination of multivariate analysis techniques was implemented to achieve a holistic understanding of the metabolome. Among all the identified circulating metabolites influenced by CAF, lysophosphatidylcholines were the most represented family. Serum sphingolipids, bile acids, acylcarnitines, unsaturated fatty acids and vitamin E and A derivatives also changed significantly in CAF-fed rats. These findings suggest that an enduring systemic inflammatory state is induced by CAF. The impact of physical training on the metabolome was less striking than the impact of diet and mainly altered circulating bile acids and glycerophospholipids. Furthermore, the serum levels of monocyte chemoattractant protein-1 were increased in CAF-fed rats, and C-reactive protein was decreased in trained groups. The leptin/adiponectin ratio, a useful marker of MetS, was increased in CAF groups, but decreased in proportion to training intensity. Multivariate analysis revealed that ST-fed animals were more susceptible to exercise-induced changes in metabolites than animals with MetS, in which

  5. The metabolome 18 years on: a concept comes of age.

    Science.gov (United States)

    Kell, Douglas B; Oliver, Stephen G

    2016-01-01

    The term 'metabolome' was introduced to the scientific literature in September 1998. To mark its 18-year-old 'coming of age', two of the co-authors of that paper review the genesis of metabolomics, whence it has come and where it may be going.

  6. A metabolomics study on human dietary intervention with apples

    DEFF Research Database (Denmark)

    Dragsted, L. O.; Kristensen, M.; Ravn-Haren, Gitte

    2009-01-01

    Metabolomics is a promising tool for searching out new biomarkers and the development of hypotheses in nutrition research. This chapter will describe the design of human dietary intervention studies where samples are collected for metabolomics analyses as well as the analytical issues and data...

  7. Metabolomics for Undergraduates: Identification and Pathway Assignment of Mitochondrial Metabolites

    Science.gov (United States)

    Marques, Ana Patrícia; Serralheiro, Maria Luisa; Ferreira, António E. N.; Freire, Ana Ponces; Cordeiro, Carlos; Silva, Marta Sousa

    2016-01-01

    Metabolomics is a key discipline in systems biology, together with genomics, transcriptomics, and proteomics. In this omics cascade, the metabolome represents the biochemical products that arise from cellular processes and is often regarded as the final response of a biological system to environmental or genetic changes. The overall screening…

  8. Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance

    Science.gov (United States)

    2012-10-01

    cancer or a history of transurethral resection of the prostate (TURP) for benign prostatic hypertrophy are excluded. Somewhat surprisingly...AD_________________ Award Number: W81XWH-11-1-0451 TITLE: Metabolomic Profiling of Prostate Cancer...29 September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance 5b

  9. Plant metabolomics and its potential application for human nutrition

    NARCIS (Netherlands)

    Hall, R.D.; Brouwer, I.D.; Fitzgerald, M.A.

    2008-01-01

    With the growing interest in the use of metabolomic technologies for a wide range of biological targets, food applications related to nutrition and quality are rapidly emerging. Metabolomics offers us the opportunity to gain deeper insights into, and have better control of, the fundamental

  10. Gas chromatography mass spectrometry : key technology in metabolomics

    NARCIS (Netherlands)

    Koek, Maud Marijtje

    2009-01-01

    Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues. Gas chromatography coupled to mass spectrometry (GC-MS) is very suitable for metabolomics analysis, as it combines high separation power with

  11. Metabolomic characteristics of arsenic-associated diabetes in a prospective cohort in Chihuahua, Mexico.

    Science.gov (United States)

    Martin, Elizabeth; González-Horta, Carmen; Rager, Julia; Bailey, Kathryn A; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Ishida, María C; Gutiérrez-Torres, Daniela S; Hernández Cerón, Roberto; Viniegra Morales, Damián; Baeza Terrazas, Francisco A; Saunders, R Jesse; Drobná, Zuzana; Mendez, Michelle A; Buse, John B; Loomis, Dana; Jia, Wei; García-Vargas, Gonzalo G; Del Razo, Luz M; Stýblo, Miroslav; Fry, Rebecca

    2015-04-01

    Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome[S

    Science.gov (United States)

    Jun, Hee-jin; Lee, Ji Hae; Kim, Jiyoung; Jia, Yaoyao; Kim, Kyoung Heon; Hwang, Kwang Yeon; Yun, Eun Ju; Do, Kyoung-Rok; Lee, Sung-Joon

    2014-01-01

    We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fluorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of PPARα. Linalool stimulation reduced cellular lipid accumulation regulating PPARα-responsive genes and significantly induced FA oxidation, and its effects were markedly attenuated by silencing PPARα expression. In mice, the oral administration of linalool for 3 weeks reduced plasma TG concentrations in Western-diet-fed C57BL/6J mice (31%, P linalool stimulation rewired global gene expression in lipid-loaded hepatocytes and that the effects of 1 mM linalool were comparable to those of 0.1 mM fenofibrate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profiles were significantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated FAs were significantly reduced in linalool-fed mice. These findings suggest that the appropriate intake of a natural aromatic compound could exert beneficial metabolic effects by regulating a cellular nutrient sensor. PMID:24752549

  13. Compliance with minimum information guidelines in public metabolomics repositories.

    Science.gov (United States)

    Spicer, Rachel A; Salek, Reza; Steinbeck, Christoph

    2017-09-26

    The Metabolomics Standards Initiative (MSI) guidelines were first published in 2007. These guidelines provided reporting standards for all stages of metabolomics analysis: experimental design, biological context, chemical analysis and data processing. Since 2012, a series of public metabolomics databases and repositories, which accept the deposition of metabolomic datasets, have arisen. In this study, the compliance of 399 public data sets, from four major metabolomics data repositories, to the biological context MSI reporting standards was evaluated. None of the reporting standards were complied with in every publicly available study, although adherence rates varied greatly, from 0 to 97%. The plant minimum reporting standards were the most complied with and the microbial and in vitro were the least. Our results indicate the need for reassessment and revision of the existing MSI reporting standards.

  14. Tools for the functional interpretation of metabolomic experiments.

    Science.gov (United States)

    Chagoyen, Monica; Pazos, Florencio

    2013-11-01

    The so-called 'omics' approaches used in modern biology aim at massively characterizing the molecular repertories of living systems at different levels. Metabolomics is one of the last additions to the 'omics' family and it deals with the characterization of the set of metabolites in a given biological system. As metabolomic techniques become more massive and allow characterizing larger sets of metabolites, automatic methods for analyzing these sets in order to obtain meaningful biological information are required. Only recently the first tools specifically designed for this task in metabolomics appeared. They are based on approaches previously used in transcriptomics and other 'omics', such as annotation enrichment analysis. These, together with generic tools for metabolic analysis and visualization not specifically designed for metabolomics will for sure be in the toolbox of the researches doing metabolomic experiments in the near future.

  15. Error Analysis and Propagation in Metabolomics Data Analysis.

    Science.gov (United States)

    Moseley, Hunter N B

    2013-01-01

    Error analysis plays a fundamental role in describing the uncertainty in experimental results. It has several fundamental uses in metabolomics including experimental design, quality control of experiments, the selection of appropriate statistical methods, and the determination of uncertainty in results. Furthermore, the importance of error analysis has grown with the increasing number, complexity, and heterogeneity of measurements characteristic of 'omics research. The increase in data complexity is particularly problematic for metabolomics, which has more heterogeneity than other omics technologies due to the much wider range of molecular entities detected and measured. This review introduces the fundamental concepts of error analysis as they apply to a wide range of metabolomics experimental designs and it discusses current methodologies for determining the propagation of uncertainty in appropriate metabolomics data analysis. These methodologies include analytical derivation and approximation techniques, Monte Carlo error analysis, and error analysis in metabolic inverse problems. Current limitations of each methodology with respect to metabolomics data analysis are also discussed.

  16. Mass spectra-based framework for automated structural elucidation of metabolome data to explore phytochemical diversity

    Directory of Open Access Journals (Sweden)

    Fumio eMatsuda

    2011-08-01

    Full Text Available A novel framework for automated elucidation of metabolite structures in liquid chromatography-mass spectrometer (LC-MS metabolome data was constructed by integrating databases. High-resolution tandem mass spectra data automatically acquired from each metabolite signal were used for database searches. Three distinct databases, KNApSAcK, ReSpect, and the PRIMe standard compound database, were employed for the structural elucidation. The outputs were retrieved using the CAS metabolite identifier for identification and putative annotation. A simple metabolite ontology system was also introduced to attain putative characterization of the metabolite signals. The automated method was applied for the metabolome data sets obtained from the rosette leaves of 20 Arabidopsis accessions. Phenotypic variations in novel Arabidopsis metabolites among these accessions could be investigated using this method.

  17. Time-resolved metabolomics reveals metabolic modulation in rice foliage

    Directory of Open Access Journals (Sweden)

    Arita Masanori

    2008-06-01

    Full Text Available Abstract Background To elucidate the interaction of dynamics among modules that constitute biological systems, comprehensive datasets obtained from "omics" technologies have been used. In recent plant metabolomics approaches, the reconstruction of metabolic correlation networks has been attempted using statistical techniques. However, the results were unsatisfactory and effective data-mining techniques that apply appropriate comprehensive datasets are needed. Results Using capillary electrophoresis mass spectrometry (CE-MS and capillary electrophoresis diode-array detection (CE-DAD, we analyzed the dynamic changes in the level of 56 basic metabolites in plant foliage (Oryza sativa L. ssp. japonica at hourly intervals over a 24-hr period. Unsupervised clustering of comprehensive metabolic profiles using Kohonen's self-organizing map (SOM allowed classification of the biochemical pathways activated by the light and dark cycle. The carbon and nitrogen (C/N metabolism in both periods was also visualized as a phenotypic linkage map that connects network modules on the basis of traditional metabolic pathways rather than pairwise correlations among metabolites. The regulatory networks of C/N assimilation/dissimilation at each time point were consistent with previous works on plant metabolism. In response to environmental stress, glutathione and spermidine fluctuated synchronously with their regulatory targets. Adenine nucleosides and nicotinamide coenzymes were regulated by phosphorylation and dephosphorylation. We also demonstrated that SOM analysis was applicable to the estimation of unidentifiable metabolites in metabolome analysis. Hierarchical clustering of a correlation coefficient matrix could help identify the bottleneck enzymes that regulate metabolic networks. Conclusion Our results showed that our SOM analysis with appropriate metabolic time-courses effectively revealed the synchronous dynamics among metabolic modules and elucidated the

  18. Metabolomics reveals significant variations in metabolites and correlations regarding the maturation of walnuts (Juglans regia L.

    Directory of Open Access Journals (Sweden)

    Guodong Rao

    2016-06-01

    Full Text Available The content of walnut metabolites is related to its nutritive value and physiological characteristics, however, comprehensive information concerning the metabolome of walnut kernels is limited. In this study we analyzed the metabolites of walnut kernels at five developmental stages from filling to ripening using GC-MS-based untargeted metabolomics; of a total 252 peaks identified, 85 metabolites were positively identified. Further statistical analysis revealed that these 85 metabolites covered different types of metabolism pathways. PCA scores revealed that the metabolic compositions of the embryo are different at each stage, while the metabolic composition of the endotesta could not be significantly separated into distinct groups. Additionally, 7225 metabolite-metabolite correlations were detected in walnut kernel by a Pearson correlation coefficient approach; during screening of the calculated correlations, 463 and 1047 were determined to be significant with r2≥0.49 and had a false discovery rate (FDR ≤0.05 in endotesta and embryo, respectively. This work provides the first comprehensive metabolomic study of walnut kernels and reveals that most of the carbohydrate and protein-derived carbon was transferred into other compounds, such as fatty acids, during the maturation of walnuts, which may potentially provide the basis for further studies on walnut kernel metabolism.

  19. Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

    2016-01-01

    Mass spectrometry-based metabolomics has become increasingly popular in molecular medicine. High-definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low-molecular-weight metabolites in bio-samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS-based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS-metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism.

    Science.gov (United States)

    Hou, Entai; Li, Xian; Liu, Zerong; Zhang, Fuchang; Tian, Zhongmin

    2018-04-01

    Fumarase catalyzes the interconversion of fumarate and l-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l-malic acid, l-aspartic acid, glycine and l-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients.

    Science.gov (United States)

    Coene, Karlien L M; Kluijtmans, Leo A J; van der Heeft, Ed; Engelke, Udo F H; de Boer, Siebolt; Hoegen, Brechtje; Kwast, Hanneke J T; van de Vorst, Maartje; Huigen, Marleen C D G; Keularts, Irene M L W; Schreuder, Michiel F; van Karnebeek, Clara D M; Wortmann, Saskia B; de Vries, Maaike C; Janssen, Mirian C H; Gilissen, Christian; Engel, Jasper; Wevers, Ron A

    2018-02-16

    The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-platform, high-resolution liquid chromatography quadrupole time of flight (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM-suspected patients. This method, which we termed "next-generation metabolic screening" (NGMS), can detect >10,000 features in each sample. In the NGMS workflow, features identified in patient and control samples are aligned using the "various forms of chromatography mass spectrometry (XCMS)" software package. Subsequently, all features are annotated using the Human Metabolome Database, and statistical testing is performed to identify significantly perturbed metabolite concentrations in a patient sample compared with controls. We propose three main modalities to analyze complex, untargeted metabolomics data. First, a targeted evaluation can be done based on identified genetic variants of uncertain significance in metabolic pathways. Second, we developed a panel of IEM-related metabolites to filter untargeted metabolomics data. Based on this IEM-panel approach, we provided the correct diagnosis for 42 of 46 IEMs. As a last modality, metabolomics data can be analyzed in an untargeted setting, which we term "open the metabolome" analysis. This approach identifies potential novel biomarkers in known IEMs and leads to identification of biomarkers for as yet unknown IEMs. We are convinced that NGMS is the way forward in laboratory diagnostics of IEMs.

  2. ORAL HYGIENE PRACTICES AND RISK OF ORAL LEUKOPLAKIA

    African Journals Online (AJOL)

    2006-04-01

    Apr 1, 2006 ... Results: The relative risk (RR) of oral leukoplakia increased gradually across the various brushing .... results of the assessment of other oral leukoplakia ... survey of persons aged 15 years and above aimed at identifying the study subjects. The screening yielded 85 oral leukoplakia cases identified on the.

  3. Biological variation of Vanilla planifolia leaf metabolome.

    Science.gov (United States)

    Palama, Tony Lionel; Fock, Isabelle; Choi, Young Hae; Verpoorte, Robert; Kodja, Hippolyte

    2010-04-01

    The metabolomic analysis of Vanilla planifolia leaves collected at different developmental stages was carried out using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis in order to evaluate their variation. Ontogenic changes of the metabolome were considered since leaves of different ages were collected at two different times of the day and in two different seasons. Principal component analysis (PCA) and partial least square modeling discriminate analysis (PLS-DA) of (1)H NMR data provided a clear separation according to leaf age, time of the day and season of collection. Young leaves were found to have higher levels of glucose, bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-isopropyltartrate (glucoside A) and bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-(2-butyl)-tartrate (glucoside B), whereas older leaves had more sucrose, acetic acid, homocitric acid and malic acid. Results obtained from PLS-DA analysis showed that leaves collected in March 2008 had higher levels of glucosides A and B as compared to those collected in August 2007. However, the relative standard deviation (RSD) exhibited by the individual values of glucosides A and B showed that those compounds vary more according to their developmental stage (50%) than to the time of day or the season in which they were collected (19%). Although morphological variations of the V. planifolia accessions were observed, no clear separation of the accessions was determined from the analysis of the NMR spectra. The results obtained in this study, show that this method based on the use of (1)H NMR spectroscopy in combination with multivariate analysis has a great potential for further applications in the study of vanilla leaf metabolome. Copyright 2009 Elsevier Ltd. All rights reserved.

  4. Challenges of metabolomics in human gut microbiota research.

    Science.gov (United States)

    Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

    2016-08-01

    The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Animal-Assisted Literacy Instruction for Students with Identified Learning Disabilities: Examining the Effects of Incorporating a Therapy Dog into Guided Oral Reading Sessions

    Science.gov (United States)

    Treat, Wendy Abigail

    2013-01-01

    Literacy acquisition is imperative to successful academic progress and to successful participation in our society. Students with identified learning disabilities are often among those who struggle to acquire literacy skills. The following dissertation shares the results of a reading intervention study in which nine students with identified…

  6. Metabolomic profiling in blood from umbilical cords of low birth weight newborns

    Directory of Open Access Journals (Sweden)

    Ivorra Carmen

    2012-07-01

    Full Text Available Abstract Background Low birth weight has been linked to an increased risk to develop obesity, type 2 diabetes, and hypertension in adult life, although the mechanisms underlying the association are not well understood. The objective was to determine whether the metabolomic profile of plasma from umbilical cord differs between low and normal birth weight newborns. Methods Fifty healthy pregnant women and their infants were selected. The eligibility criteria were being born at term and having a normal pregnancy. Pairs were grouped according to their birth weight: low birth weight (LBW, birth weight th percentile, n = 20 and control (control, birth weight between the 75th-90th percentiles, n = 30. Nuclear Magnetic Resonance (NMR was used to generate metabolic fingerprints of umbilical cord plasma samples. Simultaneously, the metabolomic profiles of the mothers were analysed. The resulting data were subjected to chemometric, principal component and partial least squares discriminant analyses. Results Umbilical cord plasma from LBW and control newborns displayed a clearly differentiated metabolic profile. Seven metabolites were identified that discriminate the LBW from the control group. LBW newborns had lower levels of choline, proline, glutamine, alanine and glucose than did the control newborns, while plasma levels of phenylalanine and citrulline were higher in LBW newborns (p Conclusions Low birth weight newborns display a differential metabolomic profile than those of normal birth weight, a finding not present in the mothers. The meaning and the potential utility of the findings as biomarkers of risk need to be addressed in future studies.

  7. Characterization of the Wheat Leaf Metabolome during Grain Filling and under Varied N-Supply

    Directory of Open Access Journals (Sweden)

    Elmien Heyneke

    2017-11-01

    Full Text Available Progress in improving crop growth is an absolute goal despite the influence multifactorial components have on crop yield and quality. An Avalon × Cadenza doubled-haploid wheat mapping population was used to study the leaf metabolome of field grown wheat at weekly intervals during the time in which the canopy contributes to grain filling, i.e., from anthesis to 5 weeks post-anthesis. Wheat was grown under four different nitrogen supplies reaching from residual soil N to a luxury over-fertilization (0, 100, 200, and 350 kg N ha−1. Four lines from a segregating doubled haploid population derived of a cross of the wheat elite cvs. Avalon and Cadenza were chosen as they showed pairwise differences in either N utilization efficiency (NUtE or senescence timing. 108 annotated metabolites of primary metabolism and ions were determined. The analysis did not provide genotype specific markers because of a remarkable stability of the metabolome between lines. We speculate that the reason for failing to identify genotypic markers might be due to insufficient genetic diversity of the wheat parents and/or the known tendency of plants to keep metabolome homeostasis even under adverse conditions through multiple adaptations and rescue mechanism. The data, however, provided a consistent catalogue of metabolites and their respective responses to environmental and developmental factors and may bode well for future systems biology approaches, and support plant breeding and crop improvement.

  8. Liver functional metabolomics discloses an action of L-leucine against Streptococcus iniae infection in tilapias.

    Science.gov (United States)

    Ma, Yan-Mei; Yang, Man-Jun; Wang, Sanying; Li, Hui; Peng, Xuan-Xian

    2015-08-01

    Streptococcus iniae seriously affects the intensive farming of tilapias. Much work has been conducted on prevention and control of S. iniae infection, but little published information on the metabolic response is available in tilapias against the bacterial infection, and no metabolic modulation way may be adopted to control this disease. The present study used GC/MS based metabolomics to characterize the metabolic profiling of tilapias infected by a lethal dose (LD50) of S. iniae and determined two characteristic metabolomes separately responsible for the survival and dying fishes. A reversal changed metabolite, decreased and increased l-leucine in the dying and survival groups, respectively, was identified as a biomarker which featured the difference between the two metabolomes. More importantly, exogenous l-leucine could be used as a metabolic modulator to elevate survival ability of tilapias infected by S. iniae. These results indicate that tilapias mount metabolic strategies to deal with bacterial infection, which can be regulated by exogenous metabolites such as l-leucine. The present study establishes an alternative way, metabolic modulation, to cope with bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Application of Stable Isotope-Assisted Metabolomics for Cell Metabolism Studies

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    Le You

    2014-03-01

    Full Text Available The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1 properly designed tracer experiments; (2 stringent sampling and quenching protocols to minimize isotopic alternations; (3 efficient metabolite separations; (4 high resolution mass spectrometry to resolve overlapping peaks and background noises; and (5 data analysis methods and databases to decipher isotopic clusters over a broad m/z range (mass-to-charge ratio. This paper overviews mass spectrometry based techniques for precise determination of metabolites and their isotopologues. It also discusses applications of isotopic approaches to track substrate utilization, identify unknown metabolites and their chemical formulas, measure metabolite concentrations, determine putative metabolic pathways, and investigate microbial community populations and their carbon assimilation patterns. In addition, 13C-metabolite fingerprinting and metabolic models can be integrated to quantify carbon fluxes (enzyme reaction rates. The fluxome, in combination with other “omics” analyses, may give systems-level insights into regulatory mechanisms underlying gene functions. More importantly, 13C-tracer experiments significantly improve the potential of low-resolution gas chromatography-mass spectrometry (GC-MS for broad-scope metabolism studies. We foresee the isotope-assisted metabolomics to be an indispensable tool in industrial biotechnology, environmental microbiology, and medical research.

  10. Studying the Differences of Bacterial Metabolome and Microbiome in the Colon between Landrace and Meihua Piglets

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    Shijuan Yan

    2017-09-01

    Full Text Available This study was conducted to compare the microbiome and metabolome differences in the colon lumen from two pig breeds with different genetic backgrounds. Fourteen weaned piglets at 30 days of age, including seven Landrace piglets (a lean-type pig breed with a fast growth rate and seven Meihua piglets (a fatty-type Chinese local pig breed with a slow growth rate, were fed the same diets for 35 days. Untargeted metabolomics analyses showed that a total of 401 metabolites differed between Landrace and Meihua. Seventy of these 401 metabolites were conclusively identified. Landrace accumulated more short-chain fatty acids (SCFAs and secondary bile acids in the colon lumen. Moreover, expression of the SCFAs transporter (solute carrier family 5 member 8, SLC5A8 and receptor (G protein-coupled receptor 41, GPR41 in the colon mucosa was higher, while the bile acids receptor (farnesoid X receptor, FXR had lower expression in Landrace compared to Meihua. The relative abundances of 8 genera and 16 species of bacteria differed significantly between Landrace and Meihua, and were closely related to the colonic concentrations of bile acids or SCFAs based on Pearson's correlation analysis. Collectively, our results demonstrate for the first time that there were differences in the colonic microbiome and metabolome between Meihua and Landrace piglets, with the most profound disparity in production of SCFAs and secondary bile acids.

  11. Metabolomics: An Essential Tool to Understand the Function of Peroxisome Proliferator–Activated Receptor Alpha

    Science.gov (United States)

    Montanez, Jessica E.; Peters, Jeffrey M.; Correll, Jared B.; Gonzalez, Frank J.; Patterson, Andrew D.

    2013-01-01

    The peroxisome proliferator–activated receptor (PPAR) family of nuclear hormone transcription factors (PPARα, PPARβ/δ, and PPARγ) is regulated by a wide array of ligands including natural and synthetic chemicals. PPARs have important roles in control of energy metabolism and are known to influence inflammation, differentiation, carcinogenesis, and chemical toxicity. As such, PPARs have been targeted as therapy for common disorders such as cancer, metabolic syndrome, obesity, and diabetes. The recent application of metabolomics, or the global, unbiased measurement of small molecules found in biofluids, or extracts from cells, tissues, or organisms, has advanced our understanding of the varied and important roles that the PPARs have in normal physiology as well as in pathophysiological processes. Continued development and refinement of analytical platforms, and the application of new bioinformatics strategies, have accelerated the widespread use of metabolomics and have allowed further integration of small molecules into systems biology. Recent studies using metabolomics to understand PPARα function, as well as to identify PPARα biomarkers associated with drug efficacy/toxicity and drug-induced liver injury, will be discussed. PMID:23197196

  12. Metabolomics reveals variation and correlation among different tissues of olive (Olea europaea L.).

    Science.gov (United States)

    Guodong, Rao; Xiaoxia, Liu; Weiwei, Zha; Wenjun, Wu; Jianguo, Zhang

    2017-09-15

    Metabolites in olives are associated with nutritional value and physiological properties. However, comprehensive information regarding the olive metabolome is limited. In this study, we identified 226 metabolites from three different tissues of olive using a non-targeted metabolomic profiling approach, of which 76 named metabolites were confirmed. Further statistical analysis revealed that these 76 metabolites covered different types of primary metabolism and some of the secondary metabolism pathways. One-way analysis of variance (ANOVA) statistical assay was performed to calculate the variations within the detected metabolites, and levels of 65 metabolites were differentially expressed in different samples. Hierarchical cluster analysis (HCA) dendrograms showed variations among different tissues that were similar to the metabolite profiles observed in new leaves and fruit. Additionally, 5776 metabolite-metabolite correlations were detected by a Pearson correlation coefficient approach. Screening of the calculated correlations revealed 3136, 3025, and 5184 were determined to metabolites and had significant correlations in three different combinations, respectively. This work provides the first comprehensive metabolomic of olive, which will provide new insights into understanding the olive metabolism, and potentially help advance studies in olive metabolic engineering. © 2017. Published by The Company of Biologists Ltd.

  13. First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach

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    Maria P. H. Koster

    2015-01-01

    Full Text Available Objective. To expand the search for preeclampsia (PE metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum. Methods. This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls (n=500 and early-onset- (EO- PE (n=68 or late-onset- (LO- PE (n=99 women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC, mean arterial pressure (MAP, and previously established biomarkers (PAPPA, PLGF, and taurine. Results. Twelve metabolites were significantly different between EO-PE women and controls, with effect levels between −18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between −8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784. The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700. Conclusion. This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO-PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation.

  14. Biogeography shaped the metabolome of the genus Espeletia: a phytochemical perspective on an Andean adaptive radiation.

    Science.gov (United States)

    Padilla-González, Guillermo F; Diazgranados, Mauricio; Da Costa, Fernando B

    2017-08-18

    The páramo ecosystem has the highest rate of diversification across plant lineages on earth, of which the genus Espeletia (Asteraceae) is a prime example. The current distribution and molecular phylogeny of Espeletia suggest the influence of Andean geography and past climatic fluctuations on the diversification of this genus. However, molecular markers have failed to reveal subtle biogeographical trends in Espeletia diversification, and metabolomic evidence for allopatric segregation in plants has never been reported. Here, we present for the first time a metabolomics approach based on liquid chromatography-mass spectrometry for revealing subtle biogeographical trends in Espeletia diversification. We demonstrate that Espeletia lineages can be distinguished by means of different metabolic fingerprints correlated to the country of origin on a global scale and to the páramo massif on a regional scale. Distinctive patterns in the accumulation of secondary metabolites according to the main diversification centers of Espeletia are also identified and a comprehensive phytochemical characterization is reported. These findings demonstrate that a variation in the metabolic fingerprints of Espeletia lineages followed the biogeography of this genus, suggesting that our untargeted metabolomics approach can be potentially used as a model to understand the biogeographic history of additional plant groups in the páramo ecosystem.

  15. Mapping an atlas of tissue-specific Drosophila melanogaster metabolomes by high resolution mass spectrometry.

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    Venkateswara R Chintapalli

    Full Text Available Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes.

  16. Metabolomics reveals variation and correlation among different tissues of olive (Olea europaea L.

    Directory of Open Access Journals (Sweden)

    Rao Guodong

    2017-09-01

    Full Text Available Metabolites in olives are associated with nutritional value and physiological properties. However, comprehensive information regarding the olive metabolome is limited. In this study, we identified 226 metabolites from three different tissues of olive using a non-targeted metabolomic profiling approach, of which 76 named metabolites were confirmed. Further statistical analysis revealed that these 76 metabolites covered different types of primary metabolism and some of the secondary metabolism pathways. One-way analysis of variance (ANOVA statistical assay was performed to calculate the variations within the detected metabolites, and levels of 65 metabolites were differentially expressed in different samples. Hierarchical cluster analysis (HCA dendrograms showed variations among different tissues that were similar to the metabolite profiles observed in new leaves and fruit. Additionally, 5776 metabolite-metabolite correlations were detected by a Pearson correlation coefficient approach. Screening of the calculated correlations revealed 3136, 3025, and 5184 were determined to metabolites and had significant correlations in three different combinations, respectively. This work provides the first comprehensive metabolomic of olive, which will provide new insights into understanding the olive metabolism, and potentially help advance studies in olive metabolic engineering.

  17. Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids

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    Caroline H. Johnson

    2017-10-01

    Full Text Available Abstract Background Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production. Methods A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. An “autonomous” mass spectrometry-based untargeted metabolomic workflow with integrative metabolic pathway analysis revealed a number of differentially regulated metabolites in primary mammary fat pad (MFP tumors compared to microdissected paired lung metastases. The study was further extended to analyze metabolites in paired normal tissues which determined the potential influence of metabolites from the microenvironment. Results Metabolomic analysis revealed that multiple metabolites were increased in metastases, including cholesterol sulfate and phospholipids (phosphatidylglycerols and phosphatidylethanolamine. Metabolite analysis of normal lung tissue in the mouse model also revealed increased levels of these metabolites compared to tissues from normal MFP and primary MFP tumors, indicating potential extracellular uptake by cancer cells in lung metastases. These results indicate a potential functional importance of cholesterol sulfate and phospholipids in propagating metastasis. In addition, metabolites involved in DNA/RNA synthesis and the TCA cycle were decreased in lung metastases compared to primary MFP tumors. Conclusions Using an integrated metabolomic workflow, this study identified a link between cholesterol sulfate and phospholipids, metabolic characteristics of the metastatic niche, and the capacity of tumor cells to colonize distant sites.

  18. Application of Stable Isotope-Assisted Metabolomics for Cell Metabolism Studies

    Science.gov (United States)

    You, Le; Zhang, Baichen; Tang, Yinjie J.

    2014-01-01

    The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1) properly designed tracer experiments; (2) stringent sampling and quenching protocols to minimize isotopic alternations; (3) efficient metabolite separations; (4) high resolution mass spectrometry to resolve overlapping peaks and background noises; and (5) data analysis methods and databases to decipher isotopic clusters over a broad m/z range (mass-to-charge ratio). This paper overviews mass spectrometry based techniques for precise determination of metabolites and their isotopologues. It also discusses applications of isotopic approaches to track substrate utilization, identify unknown metabolites and their chemical formulas, measure metabolite concentrations, determine putative metabolic pathways, and investigate microbial community populations and their carbon assimilation patterns. In addition, 13C-metabolite fingerprinting and metabolic models can be integrated to quantify carbon fluxes (enzyme reaction rates). The fluxome, in combination with other “omics” analyses, may give systems-level insights into regulatory mechanisms underlying gene functions. More importantly, 13C-tracer experiments significantly improve the potential of low-resolution gas chromatography-mass spectrometry (GC-MS) for broad-scope metabolism studies. We foresee the isotope-assisted metabolomics to be an indispensable tool in industrial biotechnology, environmental microbiology, and medical research. PMID:24957020

  19. Metabolomic Profiles of a Midge (Procladius villosimanus, Kieffer Are Associated with Sediment Contamination in Urban Wetlands

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    Katherine J. Jeppe

    2017-12-01

    Full Text Available Metabolomic techniques are powerful tools for investigating organism-environment interactions. Metabolite profiles have the potential to identify exposure or toxicity before populations are disrupted and can provide useful information for environmental assessment. However, under complex environmental scenarios, metabolomic responses to exposure can be distorted by background and/or organismal variation. In the current study, we use LC-MS (liquid chromatography-mass spectrometry and GC-MS (gas chromatography-mass spectrometry to measure metabolites of the midge Procladius villosimanus inhabiting 21 urban wetlands. These metabolites were tested against common sediment contaminants using random forest models and metabolite enrichment analysis. Sediment contaminant concentrations in the field correlated with several P. villosimanus metabolites despite natural environmental and organismal variation. Furthermore, enrichment analysis indicated that metabolite sets implicated in stress responses were enriched, pointing to specific cellular functions affected by exposure. Methionine metabolism, sugar metabolism and glycerolipid metabolism associated with total petroleum hydrocarbon and metal concentrations, while mitochondrial electron transport and urea cycle sets associated only with bifenthrin. These results demonstrate the potential for metabolomics approaches to provide useful information in field-based environmental assessments.

  20. Oral Cancer

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    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  1. Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study.

    Science.gov (United States)

    Keshteli, Ammar Hassanzadeh; van den Brand, Floris F; Madsen, Karen L; Mandal, Rupasri; Valcheva, Rosica; Kroeker, Karen I; Han, Beomsoo; Bell, Rhonda C; Cole, Janis; Hoevers, Thomas; Wishart, David S; Fedorak, Richard N; Dieleman, Levinus A

    2017-06-07

    To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis (UC) patients. In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin (FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. Twenty patients were included (mean age: 42.7 ± 14.8 years, females: 55%). Seven patients (35%) experienced a clinical relapse during the follow-up period. While 6 patients (66.7%) with normal body weight developed a clinical relapse, 1 UC patient (9.1%) who was overweight/obese relapsed during the follow-up ( P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up (0.9 oz vs 0.2 oz, P = 0.002). Five patients (71.4%) with FCP > 150 μg/g and 2 patients (15.4%) with normal FCP (≤ 150 μg/g) at baseline relapsed during the follow-up ( P = 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo.

  2. Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study

    Science.gov (United States)

    Keshteli, Ammar Hassanzadeh; van den Brand, Floris F; Madsen, Karen L; Mandal, Rupasri; Valcheva, Rosica; Kroeker, Karen I; Han, Beomsoo; Bell, Rhonda C; Cole, Janis; Hoevers, Thomas; Wishart, David S; Fedorak, Richard N; Dieleman, Levinus A

    2017-01-01

    AIM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis (UC) patients. METHODS In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin (FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. RESULTS Twenty patients were included (mean age: 42.7 ± 14.8 years, females: 55%). Seven patients (35%) experienced a clinical relapse during the follow-up period. While 6 patients (66.7%) with normal body weight developed a clinical relapse, 1 UC patient (9.1%) who was overweight/obese relapsed during the follow-up (P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up (0.9 oz vs 0.2 oz, P = 0.002). Five patients (71.4%) with FCP > 150 μg/g and 2 patients (15.4%) with normal FCP (≤ 150 μg/g) at baseline relapsed during the follow-up (P = 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. CONCLUSION A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo. PMID:28638229

  3. Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease.

    Science.gov (United States)

    Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide

    2017-07-01

    The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1 H nuclear magnetic resonance. Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia . Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease. Published by the BMJ Publishing Group Limited

  4. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

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    Joong Kyong Ahn

    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3, which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin. Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

  5. "Omics" of High Altitude Biology: A Urinary Metabolomics Biomarker Study of Rats Under Hypobaric Hypoxia.

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    Koundal, Sunil; Gandhi, Sonia; Kaur, Tanzeer; Mazumder, Avik; Khushu, Subash

    2015-12-01

    High altitude medicine is an emerging subspecialty that has crosscutting relevance for 21(st) century science and society: from sports medicine and aerospace industry to urban and rural communities living in high altitude. Recreational travel to high altitude has also become increasingly popular. Rarely has the biology of high altitude biology been studied using systems sciences and omics high-throughput technologies. In the present study, 1H-NMR-based metabolomics, along with multivariate analyses, were employed in a preclinical rat model to characterize the urinary metabolome under hypobaric hypoxia stress. Rats were exposed to simulated altitude of 6700 m above the sea level. The urine samples were collected from pre- and post-exposure (1, 3, 7, and 14 days) of hypobaric hypoxia. Metabolomics urinalysis showed alterations in TCA cycle metabolites (citrate, α-ketoglutarate), cell membrane metabolism (choline), gut micro-flora metabolism (hippurate, phenylacetylglycine), and others (N-acetyl glutamate, creatine, taurine) in response to hypobaric hypoxia. Taurine, a potential biomarker of hepatic function, was elevated after 3 days of hypobaric hypoxia, which indicates altered liver functioning. Liver histopathology confirmed the damage to tissue architecture due to hypobaric hypoxia. The metabolic pathway analysis identified taurine metabolism and TCA as important pathways that might have contributed to hypobaric hypoxia-induced pathophysiology. This study demonstrates the use of metabolomics as a promising tool for discovery and understanding of novel biochemical responses to hypobaric hypoxia exposure, providing new insight in the field of high altitude medicine and the attendant health problems that occur in response to high altitude. The findings reported here also have potential relevance for sports medicine and aviation sciences.

  6. Radiation Metabolomics: Current Status and Future Directions

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    Smrithi eSugumaran Menon

    2016-02-01

    Full Text Available Human exposure to ionizing radiation disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms and peripheral lymphocyte counts are of limited value as organ and tissue specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress-responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic ionizing radiation. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure.

  7. Integrated sampling procedure for metabolome analysis.

    Science.gov (United States)

    Schaub, Jochen; Schiesling, Carola; Reuss, Matthias; Dauner, Michael

    2006-01-01

    Metabolome analysis, the analysis of large sets of intracellular metabolites, has become an important systems analysis method in biotechnological and pharmaceutical research. In metabolic engineering, the integration of metabolome data with fluxome and proteome data into large-scale mathematical models promises to foster rational strategies for strain and cell line improvement. However, the development of reproducible sampling procedures for quantitative analysis of intracellular metabolite concentrations represents a major challenge, accomplishing (i) fast transfer of sample, (ii) efficient quenching of metabolism, (iii) quantitative metabolite extraction, and (iv) optimum sample conditioning for subsequent quantitative analysis. In addressing these requirements, we propose an integrated sampling procedure. Simultaneous quenching and quantitative extraction of intracellular metabolites were realized by short-time exposure of cells to temperatures unit operations into a one unit operation, (ii) the avoidance of any alteration of the sample due to chemical reagents in quenching and extraction, and (iii) automation. A sampling frequency of 5 s(-)(1) and an overall individual sample processing time faster than 30 s allow observing responses of intracellular metabolite concentrations to extracellular stimuli on a subsecond time scale. Recovery and reliability of the unit operations were analyzed. Impact of sample conditioning on subsequent IC-MS analysis of metabolites was examined as well. The integrated sampling procedure was validated through consistent results from steady-state metabolite analysis of Escherichia coli cultivated in a chemostat at D = 0.1 h(-)(1).

  8. Serum Metabolomics of Burkitt Lymphoma Mouse Models.

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    Fengmin Yang

    Full Text Available Burkitt lymphoma (BL is a rare and highly aggressive type of non-Hodgkin lymphoma. The mortality rate of BL patients is very high due to the rapid growth rate and frequent systemic spread of the disease. A better understanding of the pathogenesis, more sensitive diagnostic tools and effective treatment methods for BL are essential. Metabolomics, an important aspect of systems biology, allows the comprehensive analysis of global, dynamic and endogenous biological metabolites based on their nuclear magnetic resonance (NMR and mass spectrometry (MS. It has already been used to investigate the pathogenesis and discover new biomarkers for disease diagnosis and prognosis. In this study, we analyzed differences of serum metabolites in BL mice and normal mice by NMR-based metabolomics. We found that metabolites associated with energy metabolism, amino acid metabolism, fatty acid metabolism and choline phospholipid metabolism were altered in BL mice. The diagnostic potential of the metabolite differences was investigated in this study. Glutamate, glycerol and choline had a high diagnostic accuracy; in contrast, isoleucine, leucine, pyruvate, lysine, α-ketoglutarate, betaine, glycine, creatine, serine, lactate, tyrosine, phenylalanine, histidine and formate enabled the accurate differentiation of BL mice from normal mice. The discovery of abnormal metabolism and relevant differential metabolites may provide useful clues for developing novel, noninvasive approaches for the diagnosis and prognosis of BL based on these potential biomarkers.

  9. Metabolomics, a promising approach to translational research in cardiology

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    Martino Deidda

    2015-12-01

    In this article, we will provide a description of metabolomics in comparison with other, better known “omics” disciplines such as genomics and proteomics. In addition, we will review the current rationale for the implementation of metabolomics in cardiology, its basic methodology and the available data from human studies in this discipline. The topics covered will delineate the importance of being able to use the metabolomic information to understand the mechanisms of diseases from the perspective of systems biology, and as a non-invasive approach to the diagnosis, grading and treatment of cardiovascular diseases.

  10. In-silico analysis of heat shock protein 47 for identifying the novel therapeutic agents in the management of oral submucous fibrosis

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    Jayasankar P Pillai

    2014-01-01

    Conclusion: HSP47 can be a potential candidate to target, in order to control the production of abundance collagen in OSF. Hence, the binding sites of HSP47 with collagen are identified and some natural compounds with a potential to bind with these binding receptors are also recognized. These natural compounds might act as anti-HSP47 lead molecules in designing novel therapeutic agents for OSF, which are so far unavailable.

  11. New approaches for metabolomics by mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Vertes, Akos [George Washington Univ., Washington, DC (United States)

    2017-07-10

    Small molecules constitute a large part of the world around us, including fossil and some renewable energy sources. Solar energy harvested by plants and bacteria is converted into energy rich small molecules on a massive scale. Some of the worst contaminants of the environment and compounds of interest for national security also fall in the category of small molecules. The development of large scale metabolomic analysis methods lags behind the state of the art established for genomics and proteomics. This is commonly attributed to the diversity of molecular classes included in a metabolome. Unlike nucleic acids and proteins, metabolites do not have standard building blocks, and, as a result, their molecular properties exhibit a wide spectrum. This impedes the development of dedicated separation and spectroscopic methods. Mass spectrometry (MS) is a strong contender in the quest for a quantitative analytical tool with extensive metabolite coverage. Although various MS-based techniques are emerging for metabolomics, many of these approaches include extensive sample preparation that make large scale studies resource intensive and slow. New ionization methods are redefining the range of analytical problems that can be solved using MS. This project developed new approaches for the direct analysis of small molecules in unprocessed samples, as well as pushed the limits of ultratrace analysis in volume limited complex samples. The projects resulted in techniques that enabled metabolomics investigations with enhanced molecular coverage, as well as the study of cellular response to stimuli on a single cell level. Effectively individual cells became reaction vessels, where we followed the response of a complex biological system to external perturbation. We established two new analytical platforms for the direct study of metabolic changes in cells and tissues following external perturbation. For this purpose we developed a novel technique, laser ablation electrospray

  12. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  13. The MetabolomeExpress Project: enabling web-based processing, analysis and transparent dissemination of GC/MS metabolomics datasets

    Directory of Open Access Journals (Sweden)

    Carroll Adam J

    2010-07-01

    Full Text Available Abstract Background Standardization of analytical approaches and reporting methods via community-wide collaboration can work synergistically with web-tool development to result in rapid community-driven expansion of online data repositories suitable for data mining and meta-analysis. In metabolomics, the inter-laboratory reproducibility of gas-chromatography/mass-spectrometry (GC/MS makes it an obvious target for such development. While a number of web-tools offer access to datasets and/or tools for raw data processing and statistical analysis, none of these systems are currently set up to act as a public repository by easily accepting, processing and presenting publicly submitted GC/MS metabolomics datasets for public re-analysis. Description Here, we present MetabolomeExpress, a new File Transfer Protocol (FTP server and web-tool for the online storage, processing, visualisation and statistical re-analysis of publicly submitted GC/MS metabolomics datasets. Users may search a quality-controlled database of metabolite response statistics from publicly submitted datasets by a number of parameters (eg. metabolite, species, organ/biofluid etc.. Users may also perform meta-analysis comparisons of multiple independent experiments or re-analyse public primary datasets via user-friendly tools for t-test, principal components analysis, hierarchical cluster analysis and correlation analysis. They may interact with chromatograms, mass spectra and peak detection results via an integrated raw data viewer. Researchers who register for a free account may upload (via FTP their own data to the server for online processing via a novel raw data processing pipeline. Conclusions MetabolomeExpress https://www.metabolome-express.org provides a new opportunity for the general metabolomics community to transparently present online the raw and processed GC/MS data underlying their metabolomics publications. Transparent sharing of these data will allow researchers to

  14. Intergenerational environmental effects: functional signals in offspring transcriptomes and metabolomes after parental jasmonic acid treatment in apomictic dandelion.

    Science.gov (United States)

    Verhoeven, Koen J F; Verbon, Eline H; van Gurp, Thomas P; Oplaat, Carla; Ferreira de Carvalho, Julie; Morse, Alison M; Stahl, Mark; Macel, Mirka; McIntyre, Lauren M

    2018-01-01

    Parental environments can influence offspring traits. However, the magnitude of the impact of parental environments on offspring molecular phenotypes is poorly understood. Here, we test the direct effects and intergenerational effects of jasmonic acid (JA) treatment, which is involved in herbivory-induced defense signaling, on transcriptomes and metabolomes in apomictic common dandelion (Taraxacum officinale). In a full factorial crossed design with parental and offspring JA and control treatments, we performed leaf RNA-seq gene expression analysis, LC-MS metabolomics and total phenolics assays in offspring plants. Expression analysis, leveraged by a de novo assembled transcriptome, revealed an induced response to JA exposure that is consistent with known JA effects. The intergenerational effect of treatment was considerable: 307 of 858 detected JA-responsive transcripts were affected by parental JA treatment. In terms of the numbers of metabolites affected, the magnitude of the chemical response to parental JA exposure was c. 10% of the direct JA treatment response. Transcriptome and metabolome analyses both identified the phosphatidylinositol signaling pathway as a target of intergenerational JA effects. Our results highlight that parental environments can have substantial effects in offspring generations. Transcriptome and metabolome assays provide a basis for zooming in on the potential mechanisms of inherited JA effects. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  15. Induced pluripotent stem cells show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism.

    Directory of Open Access Journals (Sweden)

    John K Meissen

    Full Text Available Induced pluripotent stem cells are different from embryonic stem cells as shown by epigenetic and genomics analyses. Depending on cell types and culture conditions, such genetic alterations can lead to different metabolic phenotypes which may impact replication rates, membrane properties and cell differentiation. We here applied a comprehensive metabolomics strategy incorporating nanoelectrospray ion trap mass spectrometry (MS, gas chromatography-time of flight MS, and hydrophilic interaction- and reversed phase-liquid chromatography-quadrupole time-of-flight MS to examine the metabolome of induced pluripotent stem cells (iPSCs compared to parental fibroblasts as well as to reference embryonic stem cells (ESCs. With over 250 identified metabolites and a range of structurally unknown compounds, quantitative and statistical metabolome data were mapped onto a metabolite networks describing the metabolic state of iPSCs relative to other cell types. Overall iPSCs exhibited a striking shift metabolically away from parental fibroblasts and toward ESCs, suggestive of near complete metabolic reprogramming. Differences between pluripotent cell types were not observed in carbohydrate or hydroxyl acid metabolism, pentose phosphate pathway metabolites, or free fatty acids. However, significant differences between iPSCs and ESCs were evident in phosphatidylcholine and phosphatidylethanolamine lipid structures, essential and non-essential amino acids, and metabolites involved in polyamine biosynthesis. Together our findings demonstrate that during cellular reprogramming, the metabolome of fibroblasts is also reprogrammed to take on an ESC-like profile, but there are select unique differences apparent in iPSCs. The identified metabolomics signatures of iPSCs and ESCs may have important implications for functional regulation of maintenance and induction of pluripotency.

  16. Induced pluripotent stem cells show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism.

    Science.gov (United States)

    Meissen, John K; Yuen, Benjamin T K; Kind, Tobias; Riggs, John W; Barupal, Dinesh K; Knoepfler, Paul S; Fiehn, Oliver

    2012-01-01

    Induced pluripotent stem cells are different from embryonic stem cells as shown by epigenetic and genomics analyses. Depending on cell types and culture conditions, such genetic alterations can lead to different metabolic phenotypes which may impact replication rates, membrane properties and cell differentiation. We here applied a comprehensive metabolomics strategy incorporating nanoelectrospray ion trap mass spectrometry (MS), gas chromatography-time of flight MS, and hydrophilic interaction- and reversed phase-liquid chromatography-quadrupole time-of-flight MS to examine the metabolome of induced pluripotent stem cells (iPSCs) compared to parental fibroblasts as well as to reference embryonic stem cells (ESCs). With over 250 identified metabolites and a range of structurally unknown compounds, quantitative and statistical metabolome data were mapped onto a metabolite networks describing the metabolic state of iPSCs relative to other cell types. Overall iPSCs exhibited a striking shift metabolically away from parental fibroblasts and toward ESCs, suggestive of near complete metabolic reprogramming. Differences between pluripotent cell types were not observed in carbohydrate or hydroxyl acid metabolism, pentose phosphate pathway metabolites, or free fatty acids. However, significant differences between iPSCs and ESCs were evident in phosphatidylcholine and phosphatidylethanolamine lipid structures, essential and non-essential amino acids, and metabolites involved in polyamine biosynthesis. Together our findings demonstrate that during cellular reprogramming, the metabolome of fibroblasts is also reprogrammed to take on an ESC-like profile, but there are select unique differences apparent in iPSCs. The identified metabolomics signatures of iPSCs and ESCs may have important implications for functional regulation of maintenance and induction of pluripotency.

  17. Gaharu, from the metabolomic aspect

    International Nuclear Information System (INIS)

    Chong Saw Peng; Ahsanulkhaliqin Abdul Wahab; Mohd Fajri Osman; Shyful Azizi Abdul Rahman; Khairuddin Abdul Rahim; Mat Rasol Awang

    2006-01-01

    Agarwood, one of the timber woody plant which has the similar response as grand fir toward external invasion and is able to produce oleoresin as the secondary metabolite from plant defense system to inhibit the invader and heal the wound. Species of agarwood found in Malaysia is known as Aquilaria malaccensis, and locally known as karas or depu. A. malaccensis is valuable due to its oleoresin (gaharu). Gaharu is a product produced in the secondary metabolic pathway known as terpenoid synthesis pathway. In order to switch on this pathway, the plant defense system need to be induced and lead to the octadecanoid pathway where the linolenic acid (LA) converts to jasmonic acid (JA). Jasmonic acid is the major key to switch the plant metabolic pathway from primary metabolic pathway to secondary metabolic pathway. To prove this hypothesis, some researches on molecular study such as gene expression and protein expression are conducted to identify key components, which will lead to the manipulation of the metabolic pathway. (Author)

  18. Metabolomic analysis in severe childhood pneumonia in the Gambia, West Africa: findings from a pilot study.

    Directory of Open Access Journals (Sweden)

    Evagelia C Laiakis

    Full Text Available BACKGROUND: Pneumonia remains the leading cause of death in young children globally and improved diagnostics are needed to better identify cases and reduce case fatality. Metabolomics, a rapidly evolving field aimed at characterizing metabolites in biofluids, has the potential to improve diagnostics in a range of diseases. The objective of this pilot study is to apply metabolomic analysis to childhood pneumonia to explore its potential to improve pneumonia diagnosis in a high-burden setting. METHODOLOGY/PRINCIPAL FINDINGS: Eleven children with World Health Organization (WHO-defined severe pneumonia of non-homogeneous aetiology were selected in The Gambia, West Africa, along with community controls. Metabolomic analysis of matched plasma and urine samples was undertaken using Ultra Performance Liquid Chromatography (UPLC coupled to Time-of-Flight Mass Spectrometry (TOFMS. Biomarker extraction was done using SIMCA-P+ and Random Forests (RF. 'Unsupervised' (blinded data were analyzed by Principal Component Analysis (PCA, while 'supervised' (unblinded analysis was by Partial Least Squares-Discriminant Analysis (PLS-DA and Orthogonal Projection to Latent Structures (OPLS. Potential markers were extracted from S-plots constructed following analysis with OPLS, and markers were chosen based on their contribution to the variation and correlation within the data set. The dataset was additionally analyzed with the machine-learning algorithm RF in order to address issues of model overfitting and markers were selected based on their variable importance ranking. Unsupervised PCA analysis revealed good separation of pneumonia and control groups, with even clearer separation of the groups with PLS-DA and OPLS analysis. Statistically significant differences (p<0.05 between groups were seen with the following metabolites: uric acid, hypoxanthine and glutamic acid were higher in plasma from cases, while L-tryptophan and adenosine-5'-diphosphate (ADP were lower

  19. Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties.

    Science.gov (United States)

    Zarei, Iman; Brown, Dustin G; Nealon, Nora Jean; Ryan, Elizabeth P

    2017-12-01

    Rice bran is a functional food that has shown protection against major chronic diseases (e.g. obesity, diabetes, cardiovascular disease and cancer) in animals and humans, and these health effects have been associated with the presence of bioactive phytochemicals. Food metabolomics uses multiple chromatography and mass spectrometry platforms to detect and identify a diverse range of small molecules with high sensitivity and precision, and has not been completed for rice bran. This study utilized global, non-targeted metabolomics to identify small molecules in rice bran, and conducted a comprehensive search of peer-reviewed literature to determine bioactive compounds. Three U.S. rice varieties (Calrose, Dixiebelle, and Neptune), that have been used for human dietary intervention trials, were assessed herein for bioactive compounds that have disease control and prevention properties. The profiling of rice bran by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) identified 453 distinct phytochemicals, 209 of which were classified as amino acids, cofactors & vitamins, and secondary metabolites, and were further assessed for bioactivity. A scientific literature search revealed 65 compounds with health properties, 16 of which had not been previously identified in rice bran. This suite of amino acids, cofactors & vitamins, and secondary metabolites comprised 46% of the identified rice bran metabolome, which substantially enhanced our knowledge of health-promoting rice bran compounds provided during dietary supplementation. Rice bran metabolite profiling revealed a suite of biochemical molecules that can be further investigated and exploited for multiple nutritional therapies and medical food applications. These bioactive compounds may also be biomarkers of dietary rice bran intake. The medicinal compounds associated with rice bran can function as a network across metabolic pathways and this

  20. Molecular identification in metabolomics using infrared ion spectroscopy

    NARCIS (Netherlands)

    Martens, J.; Berden, G.; van Outersterp, R.E.; Kluijtmans, L.A.J.; Engelke, U.F.; van Karnebeek, C.D.M.; Wevers, R.A.; Oomens, J.

    2017-01-01

    Small molecule identification is a continually expanding field of research and represents the core challenge in various areas of (bio) analytical science, including metabolomics. Here, we unequivocally differentiate enantiomeric N-acetylhexosamines in body fluids using infrared ion spectroscopy,

  1. Plant single-cell and single-cell-type metabolomics.

    Science.gov (United States)

    Misra, Biswapriya B; Assmann, Sarah M; Chen, Sixue

    2014-10-01

    In conjunction with genomics, transcriptomics, and proteomics, plant metabolomics is providing large data sets that are paving the way towards a comprehensive and holistic understanding of plant growth, development, defense, and productivity. However, dilution effects from organ- and tissue-based sampling of metabolomes have limited our understanding of the intricate regulation of metabolic pathways and networks at the cellular level. Recent advances in metabolomics methodologies, along with the post-genomic expansion of bioinformatics knowledge and functional genomics tools, have allowed the gathering of enriched information on individual cells and single cell types. Here we review progress, current status, opportunities, and challenges presented by single cell-based metabolomics research in plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Spectral Relative Standard Deviation: A Practical Benchmark in Metabolomics

    Science.gov (United States)

    Metabolomics datasets, by definition, comprise of measurements of large numbers of metabolites. Both technical (analytical) and biological factors will induce variation within these measurements that is not consistent across all metabolites. Consequently, criteria are required to...

  3. Microbial metabolomics with gas chromatography/mass spectrometry

    NARCIS (Netherlands)

    Koek, M.M.; Muilwijk, B.; Werf, M.J. van der; Hankemeier, T.

    2006-01-01

    An analytical method was set up suitable for the analysis of microbial metabolomes, consisting of an oximation and silylation derivatization reaction and subsequent analysis by gas chromatography coupled to mass spectrometry. Microbial matrixes contain many compounds that potentially interfere with

  4. Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Christoph Nowak

    2016-10-01

    Full Text Available Insulin resistance (IR and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613 followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330, we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

  5. Comparative Study of Accuracy in E Speed Intra Oral Films, PSP Intra Oral Digital System and Panoramic Digital Systems (PSP&CCD for Identifying the Extent of Alveolar Bone Loss in Patients with Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    J. Moradi Haghgoo

    2014-04-01

    Full Text Available Introduction & Objective: Diagnosis of periodontal osseous lesions is very important in deter-mining prognosis, treatment plan and maintenance in the long term. This diagnosis can be achieved by using radiography. The aim of this study is to compare accuracy of E speed films, bitewing PSP, panoramic PSP and CCD for identifying the extent of destruction of al-veolar bone in chronic periodontitis. Materials & Methods: In this cross-sectional study, 272 interproximal surfaces were evaluated by 4 radiographic techniques after clinical examination by a periodontist and indication of flap surgery. The distance between CEJ and the alveolar crest was measured by Williams probe during the surgery and before osseous recontouring. These measures were considered as gold standard. This distance was measured using all 4 radiography techniques by 2 radi-ologists at standard conditions after calibration. Results: There was no significant difference between the 4 techniques. The mean distances from CEJ to alveolar crest in all techniques had no significant difference with gold standard, the least difference was in digital BW PSP and the greatest difference was in panoramic PSP. The non-measurable surfaces by E speed BW and panoramic PSP were the fewest and the most, respectively. Conclusion: Better relative accuracy with regard to variation range, mean difference of meas-ures based on gold standard and number of shown surfaces was observed in digital and conventional BW compared to digital panoramic images. (Sci J Hamadan Univ Med Sci 2014; 21 (1:41-48

  6. Stable isotope-resolved metabolomics and applications for drug development

    Science.gov (United States)

    Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

    2012-01-01

    Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

  7. Metabolomic NMR fingerprinting: an exploratory and predictive tool

    OpenAIRE

    Lauri, Ilaria

    2014-01-01

    Metabolomics is the comprehensive assessment of low molecular weight organic metabolites within biological system. The identification and characterization of several chemical species, or metabolic fingerprinting, is an emergent approach in metabolomics field that provides a valuable “snapshot” of metabolic profiles. This approach is finding an increasing number of applications in many areas including cancer research, drug discovery and food science. The combined use of NMR spectroscopy, data ...

  8. Statistical methods for handling unwanted variation in metabolomics data

    OpenAIRE

    De Livera, Alysha M.; Sysi-Aho, Marko; Jacob, Laurent; Gagnon-Bartsch, Johann A.; Castillo, Sandra; Simpson, Julie A; Speed, Terence P.

    2015-01-01

    Metabolomics experiments are inevitably subject to a component of unwanted variation, due to factors such as batch effects, long runs of samples, and confounding biological variation. Although the removal of this unwanted variation is a vital step in the analysis of metabolomics data, it is considered a gray area in which there is a recognised need to develop a better understanding of the procedures and statistical methods required to achieve statistically relevant optimal biological outcomes...

  9. Integrative metabolomics as emerging tool to study autophagy regulation

    Directory of Open Access Journals (Sweden)

    Sarah Stryeck

    2017-07-01

    Full Text Available Recent technological developments in metabolomics research have enabled in-depth characterization of complex metabolite mixtures in a wide range of biological, biomedical, environmental, agricultural, and nutritional research fields. Nuclear magnetic resonance spectroscopy and mass spectrometry are the two main platforms for performing metabolomics studies. Given their broad applicability and the systemic insight into metabolism that can be ob-tained it is not surprising that metabolomics becomes increasingly popular in basic biological research. In this review, we provide an overview on key me-tabolites, recent studies, and future opportunities for metabolomics in stud-ying autophagy regulation. Metabolites play a pivotal role in autophagy regulation and are therefore key targets for autophagy research. Given the recent success of metabolomics, it can be expected that metabolomics ap-proaches will contribute significantly to deciphering the complex regulatory mechanisms involved in autophagy in the near future and promote under-standing of autophagy and autophagy-related diseases in living cells and or-ganisms.

  10. Quality assurance procedures for mass spectrometry untargeted metabolomics. a review.

    Science.gov (United States)

    Dudzik, Danuta; Barbas-Bernardos, Cecilia; García, Antonia; Barbas, Coral

    2018-01-05

    Untargeted metabolomics, as a global approach, has already proven its great potential and capabilities for the investigation of health and disease, as well as the wide applicability for other research areas. Although great progress has been made on the feasibility of metabolomics experiments, there are still some challenges that should be faced and that includes all sources of fluctuations and bias affecting every step involved in multiplatform untargeted metabolomics studies. The identification and reduction of the main sources of unwanted variation regarding the pre-analytical, analytical and post-analytical phase of metabolomics experiments is essential to ensure high data quality. Nowadays, there is still a lack of information regarding harmonized guidelines for quality assurance as those available for targeted analysis. In this review, sources of variations to be considered and minimized along with methodologies and strategies for monitoring and improvement the quality of the results are discussed. The given information is based on evidences from different groups among our own experiences and recommendations for each stage of the metabolomics workflow. The comprehensive overview with tools presented here might serve other researchers interested in monitoring, controlling and improving the reliability of their findings by implementation of good experimental quality practices in the untargeted metabolomics study. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Oral hygiene practices and risk of oral leukoplakia | Macigo | East ...

    African Journals Online (AJOL)

    Objective: To determine the influence of oral hygiene habits and practices on the risk of developing oral leukoplakia. Design: Case control study. Setting: Githongo sublocation in Meru District. Subjects: Eighty five cases and 141 controls identified in a house-to-house screening. Results: The relative risk (RR) of oral ...

  12. Metabolomics study of Populus type propolis.

    Science.gov (United States)

    Anđelković, Boban; Vujisić, Ljubodrag; Vučković, Ivan; Tešević, Vele; Vajs, Vlatka; Gođevac, Dejan

    2017-02-20

    Herein, we propose rapid and simple spectroscopic methods to determine the chemical composition of propolis derived from various Populus species using a metabolomics approach. In order to correlate variability in Populus type propolis composition with the altitude of its collection, NMR, IR, and UV spectroscopy followed by OPLS was conducted. The botanical origin of propolis was established by comparing propolis spectral data to those of buds of various Populus species. An O2PLS method was utilized to integrate two blocks of data. According to OPLS and O2PLS, the major compounds in propolis samples, collected from temperate continental climate above 500m, were phenolic glycerides originating from P. tremula buds. Flavonoids were predominant in propolis samples collected below 400m, originating from P. nigra and P. x euramericana buds. Samples collected at 400-500m were of mixed origin, with variable amounts of all detected metabolites. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Metabolic Effects of a 24-Week Energy-Restricted Intervention Combined with Low or High Dairy Intake in Overweight Women: An NMR-Based Metabolomics Investigation

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2016-02-01

    Full Text Available We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA. A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study.

  14. Metabolomic Profiles of Dinophysis acuminata and Dinophysis acuta Using Non-Targeted High-Resolution Mass Spectrometry: Effect of Nutritional Status and Prey.

    Science.gov (United States)

    García-Portela, María; Reguera, Beatriz; Sibat, Manoella; Altenburger, Andreas; Rodríguez, Francisco; Hess, Philipp

    2018-04-26

    Photosynthetic species of the genus Dinophysis are obligate mixotrophs with temporary plastids (kleptoplastids) that are acquired from the ciliate Mesodinium rubrum , which feeds on cryptophytes of the Teleaulax-Plagioselmis-Geminigera clade. A metabolomic study of the three-species food chain Dinophysis-Mesodinium-Teleaulax was carried out using mass spectrometric analysis of extracts of batch-cultured cells of each level of that food chain. The main goal was to compare the metabolomic expression of Galician strains of Dinophysis acuminata and D. acuta that were subjected to different feeding regimes (well-fed and prey-limited) and feeding on two Mesodinium (Spanish and Danish) strains. Both Dinophysis species were able to grow while feeding on both Mesodinium strains, although differences in growth rates were observed. Toxin and metabolomic profiles of the two Dinophysis species were significantly different, and also varied between different feeding regimes and different prey organisms. Furthermore, significantly different metabolomes were expressed by a strain of D. acuminata that was feeding on different strains of the ciliate Mesodinium rubrum . Both species-specific metabolites and those common to D. acuminata and D. acuta were tentatively identified by screening of METLIN and Marine Natural Products Dictionary databases. This first metabolomic study applied to Dinophysis acuminata and D.acuta in culture establishes a basis for the chemical inventory of these species.

  15. Metabolomic Profiles of Dinophysis acuminata and Dinophysis acuta Using Non-Targeted High-Resolution Mass Spectrometry: Effect of Nutritional Status and Prey

    Directory of Open Access Journals (Sweden)

    María García-Portela

    2018-04-01

    Full Text Available Photosynthetic species of the genus Dinophysis are obligate mixotrophs with temporary plastids (kleptoplastids that are acquired from the ciliate Mesodinium rubrum, which feeds on cryptophytes of the Teleaulax-Plagioselmis-Geminigera clade. A metabolomic study of the three-species food chain Dinophysis-Mesodinium-Teleaulax was carried out using mass spectrometric analysis of extracts of batch-cultured cells of each level of that food chain. The main goal was to compare the metabolomic expression of Galician strains of Dinophysis acuminata and D. acuta that were subjected to different feeding regimes (well-fed and prey-limited and feeding on two Mesodinium (Spanish and Danish strains. Both Dinophysis species were able to grow while feeding on both Mesodinium strains, although differences in growth rates were observed. Toxin and metabolomic profiles of the two Dinophysis species were significantly different, and also varied between different feeding regimes and different prey organisms. Furthermore, significantly different metabolomes were expressed by a strain of D. acuminata that was feeding on different strains of the ciliate Mesodinium rubrum. Both species-specific metabolites and those common to D. acuminata and D. acuta were tentatively identified by screening of METLIN and Marine Natural Products Dictionary databases. This first metabolomic study applied to Dinophysis acuminata and D.acuta in culture establishes a basis for the chemical inventory of these species.

  16. Development of chemical isotope labeling liquid chromatography mass spectrometry for silkworm hemolymph metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Weifeng [Key Laboratory of Detection for Pesticide Residues, Ministry of Agriculture (China); Sericultural Research Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou (China); Han, Wei; Li, Yunong [Department of Chemistry, University of Alberta, Edmonton, Alberta (Canada); Meng, Zhiqi [Sericultural Research Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou (China); Cai, Leiming, E-mail: cailm@mail.zaas.ac.cn [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou (China); Li, Liang, E-mail: Liang.Li@ualberta.ca [Department of Chemistry, University of Alberta, Edmonton, Alberta (Canada)

    2016-10-26

    Silkworm (Bombyx mori) is a very useful target insect for evaluation of endocrine disruptor chemicals (EDCs) due to mature breeding techniques, complete endocrine system and broad basic knowledge on developmental biology. Comparative metabolomics of silkworms with and without EDC exposure offers another dimension of studying EDCs. In this work, we report a workflow on metabolomic profiling of silkworm hemolymph based on high-performance chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) and demonstrate its application in studying the metabolic changes associated with the pesticide dichlorodiphenyltrichloroethane (DDT) exposure in silkworm. Hemolymph samples were taken from mature silkworms after growing on diet that contained DDT at four different concentrations (1, 0.1, 0.01, 0.001 ppm) as well as on diet without DDT as controls. They were subjected to differential {sup 12}C-/{sup 13}C-dansyl labeling of the amine/phenol submetabolome, LC-UV quantification of the total amount of labeled metabolites for sample normalization, and LC-MS detection and relative quantification of individual metabolites in comparative samples. The total concentration of labeled metabolites did not show any significant change between four DDT-treatment groups and one control group. Multivariate statistical analysis of the metabolome data set showed that there was a distinct metabolomic separation between the five groups. Out of the 2044 detected peak pairs, 338 and 1471 metabolites have been putatively identified against the HMDB database and the EML library, respectively. 65 metabolites were identified by the dansyl library searching based on the accurate mass and retention time. Among the 65 identified metabolites, 33 positive metabolites had changes of greater than 1.20-fold or less than 0.83-fold in one or more groups with p-value of smaller than 0.05. Several useful biomarkers including serine, methionine, tryptophan, asymmetric dimethylarginine, N

  17. ROMANCE: A new software tool to improve data robustness and feature identification in CE-MS metabolomics.

    Science.gov (United States)

    González-Ruiz, Víctor; Gagnebin, Yoric; Drouin, Nicolas; Codesido, Santiago; Rudaz, Serge; Schappler, Julie

    2018-01-02

    The use of capillary electrophoresis coupled to mass spectrometry (CE-MS) in metabolomics remains an oddity compared to the widely adopted use of liquid chromatography. This technique is traditionally regarded as lacking the reproducibility to adequately identify metabolites by their migration times. The major reason is the variability of the velocity of the background electrolyte, mainly coming from shifts in the magnitude of the electroosmotic flow and from the suction caused by electrospray interfaces. The use of the effective electrophoretic mobility is one solution to overcome this issue as it is a characteristic feature of each compound. To date, such an approach has not been applied to metabolomics due to the complexity and size of CE-MS data obtained in such studies. In this paper, ROMANCE (RObust Metabolomic Analysis with Normalized CE) is introduced as a new software for CE-MS-based metabolomics. It allows the automated conversion of batches of CE-MS files with minimal user intervention. ROMANCE converts the x-axis of each MS file from the time into the effective mobility scale and the resulting files are already pseudo-aligned, present normalized peak areas and improved reproducibility, and can eventually follow existing metabolomic workflows. The software was developed in Scala, so it is multi-platform and computationally-efficient. It is available for download under a CC license. In this work, the versatility of ROMANCE was demonstrated by using data obtained in the same and in different laboratories, as well as its application to the analysis of human plasma samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Use of a pre-analysis osmolality normalisation method to correct for variable urine concentrations and for improved metabolomic analyses.

    Science.gov (United States)

    Chetwynd, Andrew J; Abdul-Sada, Alaa; Holt, Stephen G; Hill, Elizabeth M

    2016-01-29

    Metabolomics analyses of urine have the potential to provide new information on the detection and progression of many disease processes. However, urine samples can vary significantly in total solute concentration and this presents a challenge to achieve high quality metabolomic datasets and the detection of biomarkers of disease or environmental exposures. This study investigated the efficacy of pre- and post-analysis normalisation methods to analyse metabolomic datasets obtained from neat and diluted urine samples from five individuals. Urine samples were extracted by solid phase extraction (SPE) prior to metabolomic analyses using a sensitive nanoflow/nanospray LC-MS technique and the data analysed by principal component analyses (PCA). Post-analysis normalisation of the datasets to either creatinine or osmolality concentration, or to mass spectrum total signal (MSTS), revealed that sample discrimination was driven by the dilution factor of urine rather than the individual providing the sample. Normalisation of urine samples to equal osmolality concentration prior to LC-MS analysis resulted in clustering of the PCA scores plot according to sample source and significant improvements in the number of peaks common to samples of all three dilutions from each individual. In addition, the ability to identify discriminating markers, using orthogonal partial least squared-discriminant analysis (OPLS-DA), was greatly improved when pre-analysis normalisation to osmolality was compared with post-analysis normalisation to osmolality and non-normalised datasets. Further improvements for peak area repeatability were observed in some samples when the pre-analysis normalisation to osmolality was combined with a post-analysis mass spectrum total useful signal (MSTUS) or MSTS normalisation. Future adoption of such normalisation methods may reduce the variability in metabolomics analyses due to differing urine concentrations and improve the discovery of discriminating metabolites

  19. Implications of genotypic differences in the generation of a urinary metabolomics radiation signature

    Energy Technology Data Exchange (ETDEWEB)

    Laiakis, Evagelia C., E-mail: ecl28@georgetown.edu [Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington DC (United States); Pannkuk, Evan L. [Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington DC (United States); Diaz-Rubio, Maria Elena [Pediatrics, Division of Developmental Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Wang, Yi-Wen [Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington DC (United States); Mak, Tytus D. [Mass Spectrometry Data Center, National Institute of Standards and Technology (NIST), Gaithersburg MD (United States); Simbulan-Rosenthal, Cynthia M. [Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington DC (United States); Brenner, David J. [Columbia University, New York, NY (United States); Fornace, Albert J. [Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington DC (United States); Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah 22254 (Saudi Arabia)

    2016-06-15

    altered excretion patterns, although the origin of the metabolites remains to be determined. This first metabolomics study in urine from radiation exposed genetic mutant animal models provides evidence that this technology can be used to dissect the effects of genotoxic agents on metabolism by assessing easily accessible biofluids and identify biomarkers of radiation exposure. Applications of metabolomics could be incorporated in the future to further elucidate the effects of IR on the metabolism of Parp1{sup −/−} genotype by assessing individual tissues.

  20. Clinical consequences of oral mucositis.

    Science.gov (United States)

    Brown, Carlton G; Wingard, John

    2004-02-01

    To identify the clinical manifestations, risk factors, secondary complications, and assessment and management of oral mucositis. Professional journals, websites, and books. Secondary consequences of oral mucositis include infection, xerostomia, hemorrhage, and nutritional deficits. Nurses should have an extensive knowledge base about the appropriate interventions that can be used to alleviate or lessen the consequences often associated with oral mucositis.

  1. Metabolomic Profiles of Dinophysis acuminata and Dinophysis acuta Using Non-Targeted High-Resolution Mass Spectrometry

    DEFF Research Database (Denmark)

    García-Portela, María; Reguera, Beatriz; Sibat, Manoella

    2018-01-01

    Photosynthetic species of the genus Dinophysis are obligate mixotrophs with temporary plastids (kleptoplastids) that are acquired from the ciliate Mesodinium rubrum, which feeds on cryptophytes of the Teleaulax-Plagioselmis-Geminigera clade. A metabolomic study of the three-species food chain...... Dinophysis-Mesodinium-Teleaulax was carried out using mass spectrometric analysis of extracts of batch-cultured cells of each level of that food chain. The main goal was to compare the metabolomic expression of Galician strains of Dinophysis acuminata and D. acuta that were subjected to different feeding...... common to D. acuminata and D. acuta were tentatively identified by screening of METLIN and Marine Natural Products Dictionary databases. This first metabolomic study applied to Dinophysis acuminata and D.acuta in culture establishes a basis for the chemical inventory of these species....

  2. Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

    DEFF Research Database (Denmark)

    Mumme, Karen; Gray, Clint; Reynolds, Clare M.

    2016-01-01

    : Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats....... Metabolites from maternal and fetal livers, and placenta were identified using gas and liquid chromatography combined with mass spectrometry. Results: Maternal HF intake resulted in reduced fetal weight. Altered metabolite profiles were observed in the HF maternal and fetal liver, and placenta...... and fetal response to increased fat consumption seems likely to involve palmitoleic acid utilization as an adaptive response during maternal obesity....

  3. Diabetes and oral health

    OpenAIRE

    Kjersti Skjold Rønningen; Morten Enersen

    2012-01-01

    Background: Diabetes describes a group of disorders characterized by elevated levels of glucose in the blood and abnormalities of carbohydrate, fat and protein metabolism. A number of oral diseases and disorders have been associated with diabetes, and periodontitis has been identified as a possible risk factor for poor metabolic control in subjects with diabetes.Methods: This paper reviews the scientific literature to identify oral conditions that have been proposed and are known to be affect...

  4. Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

    Directory of Open Access Journals (Sweden)

    Erwin van Vliet

    Full Text Available Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress

  5. Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

    Directory of Open Access Journals (Sweden)

    Stéphane Demine

    2014-09-01

    Full Text Available Mitochondrial dysfunction(s (MDs can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy in the obesity and insulin resistance thematic.

  6. Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

    Science.gov (United States)

    Demine, Stéphane; Reddy, Nagabushana; Renard, Patricia; Raes, Martine; Arnould, Thierry

    2014-01-01

    Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. PMID:25257998

  7. Frontiers in nutrigenomics, proteomics, metabolomics and cancer prevention.

    Science.gov (United States)

    Davis, Cindy D; Milner, John

    2004-07-13

    While dietary habits continue to surface as a significant factor that may influence cancer incidence and tumor behavior, there is considerable scientific uncertainty about who will benefit most. Adequate [corrected] knowledge about how the responses depend on an individual's genetic background (nutrigenetic effects), the cumulative effects of food components on genetic expression profiles (nutritional transcriptomics and nutritional epigenomics effects), the occurrence and activity of proteins (proteomic effects) and/or the dose and temporal changes in cellular small molecular weight compounds (metabolomics effects) will [corrected] assist in identifying responders and non-responders. Expanding the information about similarities and differences in the "omic" responses across tissues will not only provide clues about specificity in response to bioactive food components but assist in the identification of surrogate tissues and biomarkers that can be used for predicting a response. Deciphering the importance of each of these potential sites of regulation will be particularly challenging but does hold promise in explaining many of the inconsistencies in the literature.

  8. Association genetics of the loblolly pine (Pinus taeda, Pinaceae) metabolome.

    Science.gov (United States)

    Eckert, Andrew J; Wegrzyn, Jill L; Cumbie, W Patrick; Goldfarb, Barry; Huber, Dudley A; Tolstikov, Vladimir; Fiehn, Oliver; Neale, David B

    2012-03-01

    The metabolome of a plant comprises all small molecule metabolites, which are produced during cellular processes. The genetic basis for metabolites in nonmodel plants is unknown, despite frequently observed correlations between metabolite concentrations and stress responses. A quantitative genetic analysis of metabolites in a nonmodel plant species is thus warranted. Here, we use standard association genetic methods to correlate 3563 single nucleotide polymorphisms (SNPs) to concentrations of 292 metabolites measured in a single loblolly pine (Pinus taeda) association population. A total of 28 single locus associations were detected, representing 24 and 20 unique SNPs and metabolites, respectively. Multilocus Bayesian mixed linear models identified 2998 additional associations for a total of 1617 unique SNPs associated to 255 metabolites. These SNPs explained sizeable fractions of metabolite heritabilities when considered jointly (56.6% on average) and had lower minor allele frequencies and magnitudes of population structure as compared with random SNPs. Modest sets of SNPs (n = 1-23) explained sizeable portions of genetic effects for many metabolites, thus highlighting the importance of multi-SNP models to association mapping, and exhibited patterns of polymorphism consistent with being linked to targets of natural selection. The implications for association mapping in forest trees are discussed. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  9. Untargeted Metabolomic Analysis of Capsicum spp. by GC-MS.

    Science.gov (United States)

    Aranha, Bianca Camargo; Hoffmann, Jessica Fernanda; Barbieri, Rosa Lia; Rombaldi, Cesar Valmor; Chaves, Fábio Clasen

    2017-09-01

    In order to conserve the biodiversity of Capsicum species and find genotypes with potential to be utilised commercially, Embrapa Clima Temperado maintains an active germplasm collection (AGC) that requires characterisation, enabling genotype selection and support for breeding programmes. The objective of this study was to characterise pepper accessions from the Embrapa Clima Temperado AGC and differentiate species based on their metabolic profile using an untargeted metabolomics approach. Cold (-20°C) methanol extraction residue of freeze-dried fruit samples was partitioned into water/methanol (A) and chloroform (B) fractions. The polar fraction (A) was derivatised and both fractions (A and B) were analysed by gas chromatography coupled to mass spectrometry (GC-MS). Data from each fraction was analysed using a multivariate principal component analysis (PCA) with XCMS software. Amino acids, sugars, organic acids, capsaicinoids, and hydrocarbons were identified. Outlying accessions including P116 (C. chinense), P46, and P76 (C. annuum) were observed in a PCA plot mainly due to their high sucrose and fructose contents. PCA also indicated a separation of P221 (C. annuum) and P200 (C. chinense), because of their high dihydrocapsaicin content. Although the metabolic profiling did not allow for grouping by species, it permitted the simultaneous identification and quantification of several compounds complementing and expanding the metabolic database of the studied Capsicum spp. in the AGC. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Singh, Brajesh; Jana, Saikat K; Ghosh, Nilanjana; Das, Soumen K; Joshi, Mamata; Bhattacharyya, Parthasarathi; Chaudhury, Koel

    2017-01-05

    Serum metabolic profiling can identify the metabolites responsible for discrimination between doxycycline treated and untreated chronic obstructive pulmonary disease (COPD) and explain the possible effect of doxycycline in improving the disease conditions. 1 H nuclear magnetic resonance (NMR)-based metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline treated COPD patients and 40 patients receiving standard therapy. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation was apparent between the pre and post doxycycline treated group. The distinguishing metabolites lactate and fatty acids were significantly down-regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and folate are further validated biochemically. Metabolic changes, such as decreased lactate level, inhibited arginase activity and lowered fatty acid level observed in COPD patients in response to add-on doxycycline treatment, reflect the anti-inflammatory action of the drug. Doxycycline as a possible therapeutic option for COPD seems promising. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Long-term fertilization determines different metabolomic profiles and responses in saplings of three rainforest tree species with different adult canopy position.

    Directory of Open Access Journals (Sweden)

    Albert Gargallo-Garriga

    Full Text Available Tropical rainforests are frequently limited by soil nutrient availability. However, the response of the metabolic phenotypic plasticity of trees to an increase of soil nutrient availabilities is poorly understood. We expected that increases in the ability of a nutrient that limits some plant processes should be detected by corresponding changes in plant metabolome profile related to such processes.We studied the foliar metabolome of saplings of three abundant tree species in a 15 year field NPK fertilization experiment in a Panamanian rainforest. The largest differences were among species and explained 75% of overall metabolome variation. The saplings of the large canopy species, Tetragastris panamensis, had the lowest concentrations of all identified amino acids and the highest concentrations of most identified secondary compounds. The saplings of the "mid canopy" species, Alseis blackiana, had the highest concentrations of amino acids coming from the biosynthesis pathways of glycerate-3P, oxaloacetate and α-ketoglutarate, and the saplings of the low canopy species, Heisteria concinna, had the highest concentrations of amino acids coming from the pyruvate synthesis pathways.The changes in metabolome provided strong evidence that different nutrients limit different species in different ways. With increasing P availability, the two canopy species shifted their metabolome towards larger investment in protection mechanisms, whereas with increasing N availability, the sub-canopy species increased its primary metabolism. The results highlighted the proportional distinct use of different nutrients by different species and the resulting different metabolome profiles in this high diversity community are consistent with the ecological niche theory.

  12. Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Victor K Tso

    Full Text Available Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD. The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20. These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies.

  13. Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

    Science.gov (United States)

    Tso, Victor K; Sydora, Beate C; Foshaug, Rae R; Churchill, Thomas A; Doyle, Jason; Slupsky, Carolyn M; Fedorak, Richard N

    2013-01-01

    Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies.

  14. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  15. Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Monica Scognamiglio

    2015-01-01

    Full Text Available An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified. Flavonoids (apigenin, quercetin, and kaempferol derivatives and phenylpropanoid derivatives (e.g., chlorogenic and rosmarinic acid are the main identified polyphenols. The richness in these metabolites could explain the biological properties ascribed to these plant species.

  16. Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics.

    Science.gov (United States)

    Scognamiglio, Monica; D'Abrosca, Brigida; Esposito, Assunta; Fiorentino, Antonio

    2015-01-01

    An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified. Flavonoids (apigenin, quercetin, and kaempferol derivatives) and phenylpropanoid derivatives (e.g., chlorogenic and rosmarinic acid) are the main identified polyphenols. The richness in these metabolites could explain the biological properties ascribed to these plant species.

  17. An Untargeted Metabolomics Survey from a Perturbation Model of Nitrogen Transformation in a Tropical Wastewater Community

    DEFF Research Database (Denmark)

    Kirkegaard, Rasmus Hansen; Angel Cokro, Anisa; Umashankar, Shivshankar

    In order to understand metabolic changes occurring during nitrogen transformation in a complex wastewater community, we conducted a metabolome time series study on a volume of freshly sourced, anoxic activated sludge, studying metabolic changes associated with the transition from anoxic to aerobic...... states. We develop analytic procedures for identifying reliable mass features that are modulated over the time, and are significantly correlated with shifts in physiochemical states. Our methods are widely applicable, and point towards to development of an eco-systems biology approach suitable...

  18. LC-QTOF/MS metabolomic profiles in human plasma after a 5-week high dietary fiber intake

    DEFF Research Database (Denmark)

    Johansson-Persson, Anna; Barri, Thaer; Ulmius, Matilda

    2013-01-01

    The objective was to investigate the alterations of plasma metabolome profiles to identify exposure and effect markers of dietary fiber intake. Subjects (n¿=¿25) aged 58.6 (1.1)¿years (mean and SD) with a body mass index of 26.6 (0.5)¿kg/m(2) were given a high fiber (HF) and a low fiber (LF) diet...

  19. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility

    NARCIS (Netherlands)

    Houten, Sander M.; Chen, Jia; Belpoggi, Fiorella; Manservisi, Fabiana; Sánchez-Guijo, Alberto; Wudy, Stefan A.; Teitelbaum, Susan L.

    2016-01-01

    The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care

  20. A liquid chromatography-mass spectrometry-based metabolome database for tomato

    NARCIS (Netherlands)

    Moco, S.I.A.; Bino, R.J.; Vorst, O.F.J.; Verhoeven, H.A.; Groot, de J.C.W.; Beek, van T.A.; Vervoort, J.J.M.; Vos, de C.H.

    2006-01-01

    For the description of the metabolome of an organism, the development of common metabolite databases is of utmost importance. Here we present the Metabolome Tomato Database (MoTo DB), a metabolite database dedicated to liquid chromatography-mass spectrometry (LC-MS)- based metabolomics of tomato

  1. Metabolome-wide association study of neovascular age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Melissa P Osborn

    Full Text Available To determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD and similarly-aged controls.Metabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape.Of the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05. A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2 revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism.These data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can

  2. Profiling of altered metabolomic states in Nicotiana tabacum cells induced by priming agents.

    Directory of Open Access Journals (Sweden)

    Msizi Innocent Mhlongo

    2016-10-01

    Full Text Available Metabolomics has developed into a valuable tool for advancing our understanding of plant metabolism. Plant innate immune defenses can be activated and enhanced so that, subsequent to being pre-sensitized, plants are able to launch a stronger and faster defense response upon exposure to pathogenic microorganisms, a phenomenon known as priming. Here, three contrasting chemical activators, namely acibenzolar-S-methyl, azelaic acid and riboflavin, were used to induce a primed state in Nicotiana tabacum cells. Identified biomarkers were then compared to responses induced by three phytohormones - abscisic acid, methyljasmonate and salicylic acid. Altered metabolomes were studied using a metabolite fingerprinting approach based on liquid chromatography and mass spectrometry. Multivariate data models indicated that these inducers cause time-dependent metabolic perturbations in the cultured cells and revealed biomarkers of which the levels are affected by these agents. A total of 34 metabolites were annotated from the mass spectral data and online databases. Venn diagrams were used to identify common biomarkers as well as those unique to a specific agent. Results implicate 20 cinnamic acid derivatives conjugated to (i quinic acid (chlorogenic acids, (ii tyramine, (iii polyamines or (iv glucose as discriminatory biomarkers of priming in tobacco cells. Functional roles for most of these metabolites in plant defense responses could thus be proposed. Metabolites induced by the activators belong to the early phenylpropanoid pathway, which indicates that different stimuli can activate similar pathways but with different metabolite fingerprints. Possible linkages to phytohormone-dependent pathways at a metabolomic level were indicated in the case of cells treated with salicylic acid and methyljasmonate. The results contribute to a better understanding of the priming phenomenon and advance our knowledge of cinnamic acid derivatives as versatile defense

  3. Metabolomics of meat exudate: Its potential to evaluate beef meat conservation and aging

    Energy Technology Data Exchange (ETDEWEB)

    Castejón, David [Centro de Asistencia a la Investigación de Resonancia Magnética Nuclear y de Espín Electrónico, Universidad Complutense de Madrid, 28040 Madrid (Spain); García-Segura, Juan Manuel [Centro de Asistencia a la Investigación de Resonancia Magnética Nuclear y de Espín Electrónico, Universidad Complutense de Madrid, 28040 Madrid (Spain); Departamento de Bioquímica y Biología Molecular I, Facultad de Químicas, Universidad Complutense de Madrid, 28040 Madrid (Spain); Escudero, Rosa [Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria. Universidad Complutense de Madrid, 28040 Madrid (Spain); Herrera, Antonio [Departamento de Química Orgánica, Facultad de Químicas, Universidad Complutense de Madrid, 28040 Madrid (Spain); Cambero, María Isabel, E-mail: icambero@vet.ucm.es [Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria. Universidad Complutense de Madrid, 28040 Madrid (Spain)

    2015-12-11

    In this study we analyzed the exudate of beef to evaluate its potential as non invasive sampling for nuclear magnetic resonance (NMR) based metabolomic analysis of meat samples. Exudate, as the natural juice from raw meat, is an easy to obtain matrix that it is usually collected in small amounts in commercial meat packages. Although meat exudate could provide complete and homogeneous metabolic information about the whole meat piece, this sample has been poorly studied. Exudates from 48 beef samples of different breeds, cattle and storage times have been studied by {sup 1}H NMR spectroscopy. The liquid exudate spectra were compared with those obtained by High Resolution Magic Angle Spinning (HRMAS) of the original meat pieces. The close correlation found between both spectra (>95% of coincident peaks in both registers; Spearman correlation coefficient = 0.945) lead us to propose the exudate as an excellent alternative analytical matrix with a view to apply meat metabolomics. 60 metabolites could be identified through the analysis of mono and bidimensional exudate spectra, 23 of them for the first time in NMR meat studies. The application of chemometric tools to analyze exudate dataset has revealed significant metabolite variations associated with meat aging. Hence, NMR based metabolomics have made it possible both to classify meat samples according to their storage time through Principal Component Analysis (PCA), and to predict that storage time through Partial Least Squares (PLS) regression. - Highlights: • NMR spectra from beef samples and their exudates are very strongly correlated. • 23 metabolites not reported in previous NMR meat studies have been identified. • Meat exudate NMR spectra allow monitoring of biochemical changes related to aging. • PCA of exudate NMR spectra classified meat samples by their storage time. • The aging of a meat sample can be predicted by PLS analysis of its exudate.

  4. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis.

    Science.gov (United States)

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-05-01

    To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to (1)H-NMR-based metabolomic analysis. Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The (1)H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.

  5. Metabolomics for functional genomics, systems biology, and biotechnology.

    Science.gov (United States)

    Saito, Kazuki; Matsuda, Fumio

    2010-01-01

    Metabolomics now plays a significant role in fundamental plant biology and applied biotechnology. Plants collectively produce a huge array of chemicals, far more than are produced by most other organisms; hence, metabolomics is of great importance in plant biology. Although substantial improvements have been made in the field of metabolomics, the uniform annotation of metabolite signals in databases and informatics through international standardization efforts remains a challenge, as does the development of new fields such as fluxome analysis and single cell analysis. The principle of transcript and metabolite cooccurrence, particularly transcriptome coexpression network analysis, is a powerful tool for decoding the function of genes in Arabidopsis thaliana. This strategy can now be used for the identification of genes involved in specific pathways in crops and medicinal plants. Metabolomics has gained importance in biotechnology applications, as exemplified by quantitative loci analysis, prediction of food quality, and evaluation of genetically modified crops. Systems biology driven by metabolome data will aid in deciphering the secrets of plant cell systems and their application to biotechnology.

  6. [Development of Plant Metabolomics and Medicinal Plant Genomics].

    Science.gov (United States)

    Saito, Kazuki

    2018-01-01

     A variety of chemicals produced by plants, often referred to as 'phytochemicals', have been used as medicines, food, fuels and industrial raw materials. Recent advances in the study of genomics and metabolomics in plant science have accelerated our understanding of the mechanisms, regulation and evolution of the biosynthesis of specialized plant products. We can now address such questions as how the metabolomic diversity of plants is originated at the levels of genome, and how we should apply this knowledge to drug discovery, industry and agriculture. Our research group has focused on metabolomics-based functional genomics over the last 15 years and we have developed a new research area called 'Phytochemical Genomics'. In this review, the development of a research platform for plant metabolomics is discussed first, to provide a better understanding of the chemical diversity of plants. Then, representative applications of metabolomics to functional genomics in a model plant, Arabidopsis thaliana, are described. The extension of integrated multi-omics analyses to non-model specialized plants, e.g., medicinal plants, is presented, including the identification of novel genes, metabolites and networks for the biosynthesis of flavonoids, alkaloids, sulfur-containing metabolites and terpenoids. Further, functional genomics studies on a variety of medicinal plants is presented. I also discuss future trends in pharmacognosy and related sciences.

  7. Mixing omics: combining genetics and metabolomics to study rheumatic diseases.

    Science.gov (United States)

    Menni, Cristina; Zierer, Jonas; Valdes, Ana M; Spector, Tim D

    2017-03-01

    Metabolomics is an exciting field in systems biology that provides a direct readout of the biochemical activities taking place within an individual at a particular point in time. Metabolite levels are influenced by many factors, including disease status, environment, medications, diet and, importantly, genetics. Thanks to their dynamic nature, metabolites are useful for diagnosis and prognosis, as well as for predicting and monitoring the efficacy of treatments. At the same time, the strong links between an individual's metabolic and genetic profiles enable the investigation of pathways that underlie changes in metabolite levels. Thus, for the field of metabolomics to yield its full potential, researchers need to take into account the genetic factors underlying the production of metabolites, and the potential role of these metabolites in disease processes. In this Review, the methodological aspects related to metabolomic profiling and any potential links between metabolomics and the genetics of some of the most common rheumatic diseases are described. Links between metabolomics, genetics and emerging fields such as the gut microbiome and proteomics are also discussed.

  8. Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field

    Science.gov (United States)

    Denihan, Niamh M.; Boylan, Geraldine B.; Murray, Deirdre M.

    2015-01-01

    Metabolomics, the latest “omic” technology, is defined as the comprehensive study of all low molecular weight biochemicals, “metabolites” present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field. PMID:25802843

  9. The Chemical Translation Service—a web-based tool to improve standardization of metabolomic reports

    Science.gov (United States)

    Wohlgemuth, Gert; Haldiya, Pradeep Kumar; Willighagen, Egon; Kind, Tobias; Fiehn, Oliver

    2010-01-01

    Summary: Metabolomic publications and databases use different database identifiers or even trivial names which disable queries across databases or between studies. The best way to annotate metabolites is by chemical structures, encoded by the International Chemical Identifier code (InChI) or InChIKey. We have implemented a web-based Chemical Translation Service that performs batch conversions of the most common compound identifiers, including CAS, CHEBI, compound formulas, Human Metabolome Database HMDB, InChI, InChIKey, IUPAC name, KEGG, LipidMaps, PubChem CID+SID, SMILES and chemical synonym names. Batch conversion downloads of 1410 CIDs are performed in 2.5 min. Structures are automatically displayed. Implementation: The software was implemented in Groovy and JAVA, the web frontend was implemented in GRAILS and the database used was PostgreSQL. Availability: The source code and an online web interface are freely available. Chemical Translation Service (CTS): http://cts.fiehnlab.ucdavis.edu Contact: ofiehn@ucdavis.edu PMID:20829444

  10. The Chemical Translation Service--a web-based tool to improve standardization of metabolomic reports.

    Science.gov (United States)

    Wohlgemuth, Gert; Haldiya, Pradeep Kumar; Willighagen, Egon; Kind, Tobias; Fiehn, Oliver

    2010-10-15

    Metabolomic publications and databases use different database identifiers or even trivial names which disable queries across databases or between studies. The best way to annotate metabolites is by chemical structures, encoded by the International Chemical Identifier code (InChI) or InChIKey. We have implemented a web-based Chemical Translation Service that performs batch conversions of the most common compound identifiers, including CAS, CHEBI, compound formulas, Human Metabolome Database HMDB, InChI, InChIKey, IUPAC name, KEGG, LipidMaps, PubChem CID+SID, SMILES and chemical synonym names. Batch conversion downloads of 1410 CIDs are performed in 2.5 min. Structures are automatically displayed. The software was implemented in Groovy and JAVA, the web frontend was implemented in GRAILS and the database used was PostgreSQL. The source code and an online web interface are freely available. Chemical Translation Service (CTS): http://cts.fiehnlab.ucdavis.edu ofiehn@ucdavis.edu

  11. Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.

    Science.gov (United States)

    Zhao, Dong-Sheng; Jiang, Li-Long; Fan, Ya-Xi; Wang, Ling-Li; Li, Zhuo-Qing; Shi, Wei; Li, Ping; Li, Hui-Jun

    2017-10-16

    The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. In the present study, we aimed to profile entire endogenous metabolites in a biological system using a multisample integrated metabolomics strategy. Our findings offered additional insights into the molecular mechanism of the DBR-induced hepatotoxicity. We identified different metabolites from rat plasma, urine, and feces by employing gas chromatography-mass spectrometry in combination with multivariate analysis. In total, 55 metabolites distributed in 33 metabolic pathways were identified as being significantly altered in DBR-treated rats. Correlation network analysis revealed that the hub metabolites of hepatotoxicity were mainly associated with amino acid, bile acid, purine, pyrimidine, lipid, and energy metabolism. As such, DBR affected the physiological and biological functions of liver via the regulation of multiple metabolic pathways to an abnormal state. Notably, our findings also demonstrated that the multisample integrated metabolomics strategy has a great potential to identify more biomarkers and pathways in order to elucidate the mechanistic complexity of toxicity of traditional Chinese medicine.

  12. Metabolomic Tools to Assess the Chemistry and Bioactivity of Endophytic Aspergillus Strain.

    Science.gov (United States)

    Tawfike, Ahmed F; Tate, Rothwelle; Abbott, Gráinne; Young, Louise; Viegelmann, Christina; Schumacher, Marc; Diederich, Marc; Edrada-Ebel, RuAngelie

    2017-10-01

    Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology that may find applications as pharmaceutical and agrochemical drugs. In this study, a combination of metabolomics and bioactivity-guided approaches were employed to isolate secondary metabolites with cytotoxicity against cancer cells from an endophytic Aspergillus aculeatus. The endophyte was isolated from the Egyptian medicinal plant Terminalia laxiflora and identified using molecular biological methods. Metabolomics and dereplication studies were accomplished by utilizing the MZmine software coupled with the universal Dictionary of Natural Products database. Metabolic profiling, with aid of multivariate data analysis, was performed at different stages of the growth curve to choose the optimized method suitable for up-scaling. The optimized culture method yielded a crude extract abundant with biologically-active secondary metabolites. Crude extracts were fractionated using different high-throughput chromatographic techniques. Purified compounds were identified by HR-ESI-MS, 1D- and 2D-NMR. This study introduced a new method of dereplication utilizing both high-resolution mass spectrometry and NMR spectroscopy. The metabolites were putatively identified by applying a chemotaxonomic filter. We also present a short review on the diverse chemistry of terrestrial endophytic strains of Aspergillus, which has become a part of our dereplication work and this will be of wide interest to those working in this field. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  13. Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps.

    Science.gov (United States)

    Deng, Lu; Chang, David; Foshaug, Rae R; Eisner, Roman; Tso, Victor K; Wishart, David S; Fedorak, Richard N

    2017-06-22

    Background: Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, low cost, and high sensitivity) mass spectrometry (MS)-based urine metabolomic test for the detection of adenomatous polyps. Methods : Prospective urine and stool samples were collected from 685 participants enrolled in a colorectal cancer screening program to undergo colonoscopy examination. Statistical analysis was performed on 69 urine metabolites measured by one-dimensional nuclear magnetic resonance spectroscopy to identify key metabolites. A targeted MS assay was then developed to quantify the key metabolites in urine. A MS-based urine metabolomic diagnostic test for adenomatous polyps was established using 67% samples (un-blinded training set) and validated using the remaining 33% samples (blinded testing set). Results : The MS-based urine metabolomic test identifies patients with colonic adenomatous polyps with an AUC of 0.692, outperforming the NMR based predictor with an AUC of 0.670. Conclusion : Here we describe a clinically scalable MS-based urine metabolomic test that identifies patients with adenomatous polyps at a higher level of sensitivity (86%) over current fecal-based tests (<18%).

  14. Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps

    Directory of Open Access Journals (Sweden)

    Lu Deng

    2017-06-01

    Full Text Available Background: Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, low cost, and high sensitivity mass spectrometry (MS-based urine metabolomic test for the detection of adenomatous polyps. Methods: Prospective urine and stool samples were collected from 685 participants enrolled in a colorectal cancer screening program to undergo colonoscopy examination. Statistical analysis was performed on 69 urine metabolites measured by one-dimensional nuclear magnetic resonance spectroscopy to identify key metabolites. A targeted MS assay was then developed to quantify the key metabolites in urine. A MS-based urine metabolomic diagnostic test for adenomatous polyps was established using 67% samples (un-blinded training set and validated using the remaining 33% samples (blinded testing set. Results: The MS-based urine metabolomic test identifies patients with colonic adenomatous polyps with an AUC of 0.692, outperforming the NMR based predictor with an AUC of 0.670. Conclusion: Here we describe a clinically scalable MS-based urine metabolomic test that identifies patients with adenomatous polyps at a higher level of sensitivity (86% over current fecal-based tests (<18%.

  15. Personalized medicine for mucositis: Bayesian networks identify unique gene clusters which predict the response to gamma-D-glutamyl-L-tryptophan (SCV-07) for the attenuation of chemoradiation-induced oral mucositis.

    Science.gov (United States)

    Alterovitz, Gil; Tuthill, Cynthia; Rios, Israel; Modelska, Katharina; Sonis, Stephen

    2011-10-01

    Gamma-D-glutamyl-L-tryptophan (SCV-07) demonstrated an overall efficacy signal in ameliorating oral mucositis (OM) in a clinical trial of head and neck cancer patients. However, not all SCV-07-treated subjects responded positively. Here we determined if specific gene clusters could discriminate between subjects who responded to SCV-07 and those who did not. Microarrays were done using peripheral blood RNA obtained at screening and on the last day of radiation from 28 subjects enrolled in the SCV-07 trial. An analytical technique was applied that relied on learned Bayesian networks to identify gene clusters which discriminated between individuals who received SCV-07 and those who received placebo, and which differentiated subjects for whom SCV-07 was an effective OM intervention from those for whom it was not. We identified 107 genes that discriminated SCV-07 responders from non-responders using four models and applied Akaike Information Criteria (AIC) and Bayes Factor (BF) analysis to evaluate predictive accuracy. AIC were superior to BF: the accuracy of predicting placebo vs. treatment was 78% using BF, but 91% using the AIC score. Our ability to differentiate responders from non-responders using the AIC score was dramatic and ranged from 93% to 100% depending on the dataset that was evaluated. Predictive Bayesian networks were identified and functional cluster analyses were performed. A specific 10 gene cluster was a critical contributor to the predictability of the dataset. Our results demonstrate proof of concept in which the application of a genomics-based analytical paradigm was capable of discriminating responders and non-responders for an OM intervention. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. New findings on the in vivo antioxidant activity of Curcuma longa extract by an integrated (1)H NMR and HPLC-MS metabolomic approach.

    Science.gov (United States)

    Dall'Acqua, Stefano; Stocchero, Matteo; Boschiero, Irene; Schiavon, Mariano; Golob, Samuel; Uddin, Jalal; Voinovich, Dario; Mammi, Stefano; Schievano, Elisabetta

    2016-03-01

    Curcuminoids possess powerful antioxidant activity as demonstrated in many chemical in vitro tests and in several in vivo trials. Nevertheless, the mechanism of this activity is not completely elucidated and studies on the in vivo antioxidant effects are still needed. Metabolomics may be used as an attractive approach for such studies and in this paper, we describe the effects of oral administration of a Curcuma longa L. extract (150 mg/kg of total curcuminoids) to 12 healthy rats with particular attention to urinary markers of oxidative stress. The experiment was carried out over 33 days and changes in the 24-h urine samples metabolome were evaluated by (1)H NMR and HPLC-MS. Both techniques produced similar representations for the collected samples confirming our previous study. Modifications of the urinary metabolome lead to the observation of different variables proving the complementarity of (1)H NMR and HPLC-MS for metabolomic purposes. The urinary levels of allantoin, m-tyrosine, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine were decreased in the treated group thus supporting an in vivo antioxidant effect of the oral administration of Curcuma extract to healthy rats. On the other hand, urinary TMAO levels were higher in the treated compared to the control group suggesting a role of curcumin supplementation on microbiota or on TMAO urinary excretion. Furthermore, the urinary levels of the sulphur containing compounds taurine and cystine were also changed suggesting a role for such constituents in the biochemical pathways involved in Curcuma extract bioactivity and indicating the need for further investigation on the complex role of antioxidant curcumin effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Genetic basis of metabolome variation in yeast.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Breunig

    2014-03-01

    Full Text Available Metabolism, the conversion of nutrients into usable energy and biochemical building blocks, is an essential feature of all cells. The genetic factors responsible for inter-individual metabolic variability remain poorly understood. To investigate genetic causes of metabolome variation, we measured the concentrations of 74 metabolites across ~ 100 segregants from a Saccharomyces cerevisiae cross by liquid chromatography-tandem mass spectrometry. We found 52 quantitative trait loci for 34 metabolites. These included linkages due to overt changes in metabolic genes, e.g., linking pyrimidine intermediates to the deletion of ura3. They also included linkages not directly related to metabolic enzymes, such as those for five central carbon metabolites to ira2, a Ras/PKA pathway regulator, and for the metabolites, S-adenosyl-methionine and S-adenosyl-homocysteine to slt2, a MAP kinase involved in cell wall integrity. The variant of ira2 that elevates metabolite levels also increases glucose uptake and ethanol secretion. These results highlight specific examples of genetic variability, including in genes without prior known metabolic regulatory function, that impact yeast metabolism.

  18. Metabolomic evaluation of ginsenosides distribution in Panax genus (Panax ginseng and Panax quinquefolius) using multivariate statistical analysis.

    Science.gov (United States)

    Pace, Roberto; Martinelli, Ernesto Marco; Sardone, Nicola; D E Combarieu, Eric

    2015-03-01

    Ginseng is any one of the eleven species belonging to the genus Panax of the family Araliaceae and is found in North America and in eastern Asia. Ginseng is characterized by the presence of ginsenosides. Principally Panax ginseng and Panax quinquefolius are the adaptogenic herbs and are commonly distributed as health food markets. In the present study high performance liquid chromatography has been used to identify and quantify ginsenosides in the two subject species and the different parts of the plant (roots, neck, leaves, flowers, fruits). The power of this chromatographic technique to evaluate the identity of botanical material and to distinguishing different part of the plants has been investigated with metabolomic technique such as principal component analysis. Metabolomics provide a good opportunity for mining useful chemical information from the chromatographic data set resulting an important tool for quality evaluation of medicinal plants in the authenticity, consistency and efficacy. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Metabolomic analysis of Echinacea spp. by 1H nuclear magnetic resonance spectrometry and multivariate data analysis technique.

    Science.gov (United States)

    Frédérich, Michel; Jansen, Céline; de Tullio, Pascal; Tits, Monique; Demoulin, Vincent; Angenot, Luc

    2010-01-01

    The genus Echinacea (Asteraceae) comprises about 10 species originally distributed in North America. Three species are very well known as they are used worldwide as medicinal plants: Echinacea purpurea, E. pallida, E. angustifolia. To discriminate between these three Echinacea species and E. simulata by (1)H NMR-based metabolomics. (1)H NMR and multivariate analysis techniques were applied to diverse Echinacea plants including roots and aerial parts, authentic plants, commercial plants and commercial dry extracts. Using the (1)H NMR metabolomics, it was possible, without previous evaporation or separation steps, to obtain a metabolic fingerprint to distinguish between species. A clear distinction between the three pharmaceutical species was possible and some useful metabolites were identified. (c) 2009 John Wiley & Sons, Ltd.

  20. Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y.

    Science.gov (United States)

    Blighe, Kevin; Chawes, Bo L; Kelly, Rachel S; Mirzakhani, Hooman; McGeachie, Michael; Litonjua, Augusto A; Weiss, Scott T; Lasky-Su, Jessica A

    2017-10-01

    Background: Vitamin D deficiency is implicated in a range of common complex diseases that may be prevented by gestational vitamin D repletion. Understanding the metabolic mechanisms related to in utero vitamin D exposure may therefore shed light on complex disease susceptibility. Objective: The goal was to analyze the programming role of in utero vitamin D exposure on children's metabolomics profiles. Design: First, unsupervised clustering was done with plasma metabolomics profiles from a case-control subset of 245 children aged 3 y with and without asthma from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), in which pregnant women were randomly assigned to vitamin D supplementation or placebo. Thereafter, we analyzed the influence of maternal pre- and postsupplement vitamin D concentrations on cluster membership. Finally, we used the metabolites driving the clustering of children to identify the dominant metabolic pathways that were influential in each cluster. Results: We identified 3 clusters of children characterized by 1 ) high concentrations of fatty acids and amines and low maternal postsupplement vitamin D (mean ± SD; 27.5 ± 11.0 ng/mL), 2 ) high concentrations of amines, moderate concentrations of fatty acids, and normal maternal postsupplement vitamin D (34.0 ± 14.1 ng/mL), and 3 ) low concentrations of fatty acids, amines, and normal maternal postsupplement vitamin D (35.2 ± 15.9 ng/mL). Adjusting for sample storage time, maternal age and education, and both child asthma and vitamin D concentration at age 3 y did not modify the association between maternal postsupplement vitamin D and cluster membership ( P = 0.0014). Maternal presupplement vitamin D did not influence cluster membership, whereas the combination of pre- and postsupplement concentrations did ( P = 0.03). Conclusions: Young children can be clustered into distinct biologically meaningful groups by their metabolomics profiles. The clusters differed in concentrations of

  1. Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

    Science.gov (United States)

    Cui, Liang; Hou, Jue; Fang, Jinling; Lee, Yie Hou; Costa, Vivian Vasconcelos; Wong, Lan Hiong; Chen, Qingfeng; Ooi, Eng Eong; Tannenbaum, Steven R; Chen, Jianzhu; Ong, Choon Nam

    2017-07-15

    Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly

  2. Serum Metabolomics in Rats after Acute Paraquat Poisoning.

    Science.gov (United States)

    Wang, Zhiyi; Ma, Jianshe; Zhang, Meiling; Wen, Congcong; Huang, Xueli; Sun, Fa; Wang, Shuanghu; Hu, Lufeng; Lin, Guanyang; Wang, Xianqin

    2015-01-01

    Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based on GC/MS to evaluate the effects of acute paraquat poisoning on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the level of octadecanoic acid, L-serine, L-threonine, L-valine, and glycerol in the acute paraquat poisoning group (36 mg/kg) increased, while the levels of hexadecanoic acid, D-galactose, and decanoic acid decreased. These findings provide an overview of systematic responses to paraquat exposure and metabolomic insight into the toxicological mechanism of paraquat. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate the mechanism of acute paraquat poisoning through the exploration of biomarkers.

  3. Bioengineering silicon quantum dot theranostics using a network analysis of metabolomic and proteomic data in cardiac ischemia.

    Science.gov (United States)

    Erogbogbo, Folarin; May, Jasmine; Swihart, Mark; Prasad, Paras N; Smart, Katie; Jack, Seif El; Korcyk, Dariusz; Webster, Mark; Stewart, Ralph; Zeng, Irene; Jullig, Mia; Bakeev, Katherine; Jamieson, Michelle; Kasabov, Nikolas; Gopalan, Banu; Liang, Linda; Hu, Raphael; Schliebs, Stefan; Villas-Boas, Silas; Gladding, Patrick

    2013-01-01

    Metabolomic profiling is ideally suited for the analysis of cardiac metabolism in healthy and diseased states. Here, we show that systematic discovery of biomarkers of ischemic preconditioning using metabolomics can be translated to potential nanotheranostics. Thirty-three patients underwent percutaneous coronary intervention (PCI) after myocardial infarction. Blood was sampled from catheters in the coronary sinus, aorta and femoral vein before coronary occlusion and 20 minutes after one minute of coronary occlusion. Plasma was analysed using GC-MS metabolomics and iTRAQ LC-MS/MS proteomics. Proteins and metabolites were mapped into the Metacore network database (GeneGo, MI, USA) to establish functional relevance. Expression of 13 proteins was significantly different (p<0.05) as a result of PCI. Included amongst these was CD44, a cell surface marker of reperfusion injury. Thirty-eight metabolites were identified using a targeted approach. Using PCA, 42% of their variance was accounted for by 21 metabolites. Multiple metabolic pathways and potential biomarkers of cardiac ischemia, reperfusion and preconditioning were identified. CD44, a marker of reperfusion injury, and myristic acid, a potential preconditioning agent, were incorporated into a nanotheranostic that may be useful for cardiovascular applications. Integrating biomarker discovery techniques into rationally designed nanoconstructs may lead to improvements in disease-specific diagnosis and treatment.

  4. Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

    Directory of Open Access Journals (Sweden)

    Susanna K. P. Lau

    2016-02-01

    Full Text Available To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6, lysophosphatidylethanolamine (LysoPE (n = 3, sphingomyelins (SM (n = 2 and phosphatidylcholine (PC (n = 1, with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0 possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%, and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%. Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0 representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

  5. The Lipopolysaccharide-Induced Metabolome Signature in Arabidopsis thaliana Reveals Dynamic Reprogramming of Phytoalexin and Phytoanticipin Pathways.

    Science.gov (United States)

    Finnegan, Tarryn; Steenkamp, Paul A; Piater, Lizelle A; Dubery, Ian A

    Lipopolysaccharides (LPSs), as MAMP molecules, trigger the activation of signal transduction pathways involved in defence. Currently, plant metabolomics is providing new dimensions into understanding the intracellular adaptive responses to external stimuli. The effect of LPS on the metabolomes of Arabidopsis thaliana cells and leaf tissue was investigated over a 24 h period. Cellular metabolites and those secreted into the medium were extracted with methanol and liquid chromatography coupled to mass spectrometry was used for quantitative and qualitative analyses. Multivariate statistical data analyses were used to extract interpretable information from the generated multidimensional LC-MS data. The results show that LPS perception triggered differential changes in the metabolomes of cells and leaves, leading to variation in the biosynthesis of specialised secondary metabolites. Time-dependent changes in metabolite profiles were observed and biomarkers associated with the LPS-induced response were tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indole-and other glucosinolates, indole derivatives, camalexin as well as cinnamic acid derivatives and other phenylpropanoids. These annotated metabolites indicate dynamic reprogramming of metabolic pathways that are functionally related towards creating an enhanced defensive capacity. The results reveal new insights into the mode of action of LPS as an activator of plant innate immunity, broadens knowledge about the defence metabolite pathways involved in Arabidopsis responses to LPS, and identifies specialised metabolites of functional importance that can be employed to enhance immunity against pathogen infection.

  6. Navigating freely-available software tools for metabolomics analysis.

    Science.gov (United States)

    Spicer, Rachel; Salek, Reza M; Moreno, Pablo; Cañueto, Daniel; Steinbeck, Christoph

    2017-01-01

    The field of metabolomics has expanded greatly over the past two decades, both as an experimental science with applications in many areas, as well as in regards to data standards and bioinformatics software tools. The diversity of experimental designs and instrumental technologies used for metabolomics has led to the need for distinct data analysis methods and the development of many software tools. To compile a comprehensive list of the most widely used freely available software and tools that are used primarily in metabolomics. The most widely used tools were selected for inclusion in the review by either ≥ 50 citations on Web of Science (as of 08/09/16) or the use of the tool being reported in the recent Metabolomics Society survey. Tools were then categorised by the type of instrumental data (i.e. LC-MS, GC-MS or NMR) and the functionality (i.e. pre- and post-processing, statistical analysis, workflow and other functions) they are designed for. A comprehensive list of the most used tools was compiled. Each tool is discussed within the context of its application domain and in relation to comparable tools of the same domain. An extended list including additional tools is available at https://github.com/RASpicer/MetabolomicsTools which is classified and searchable via a simple controlled vocabulary. This review presents the most widely used tools for metabolomics analysis, categorised based on their main functionality. As future work, we suggest a direct comparison of tools' abilities to perform specific data analysis tasks e.g. peak picking.

  7. The impact of ambient air pollution on the human blood metabolome.

    Science.gov (United States)

    Vlaanderen, J J; Janssen, N A; Hoek, G; Keski-Rahkonen, P; Barupal, D K; Cassee, F R; Gosens, I; Strak, M; Steenhof, M; Lan, Q; Brunekreef, B; Scalbert, A; Vermeulen, R C H

    2017-07-01

    Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution. We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2h before and 2 and 18h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study. We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism. This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The Swine Plasma Metabolome Chronicles "Many Days" Biological Timing and Functions Linked to Growth

    Science.gov (United States)

    Bromage, Timothy G.; Idaghdour, Youssef; Lacruz, Rodrigo S.; Crenshaw, Thomas D.; Ovsiy, Olexandra; Rotter, Björn; Hoffmeier, Klaus; Schrenk, Friedemann

    2016-01-01

    The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that

  9. Metabolic responses of the isopod Porcellionides pruinosus to nickel exposure assessed by (1)H NMR metabolomics.

    Science.gov (United States)

    Ferreira, Nuno G C; Saborano, Raquel; Morgado, Rui; Cardoso, Diogo N; Rocha, Cláudia M; Soares, Amadeu M V M; Loureiro, Susana; Duarte, Iola F

    2016-03-30

    This work aimed at characterizing the metabolome of the isopod Porcellionides pruinosus and at assessing its variations over 14 days under laboratory culture conditions and upon exposure to the contaminant metal Nickel (Ni). The spectral profiles obtained by (1)H NMR spectroscopy were thoroughly assigned and subjected to multivariate analysis in order to highlight consistent changes. Over 50 metabolites could be identified, providing considerable new knowledge on the metabolome of these model organisms. Several metabolites changed non-linearly with Ni dose and exposure time, showing distinct variation patterns for initial (4 days) and later time points (7 and 14 days). In particular, at day 4, several amino acids were increased and sugars were decreased (compared to controls), whereas these variations were inverted for longer exposure, possibly reflecting earlier and more intensive moulting. Other variations, namely in betaines and choline-containing compounds, were suggested to relate with osmoregulation and detoxification mechanisms. Ni also had a marked effect on several nucleotides (increased upon exposure) and a moderate impact on lipids (decreased upon exposure). Overall, this study has provided new information on the Ni-induced metabolic adaptations of the P. pruinosus isopod, paving the way for improved mechanistic understanding of how these model organisms handle soil contamination. This study provided, for the first time to our knowledge, a detailed picture of the NMR-detectable metabolome of terrestrial isopods and of its fluctuations in time and upon exposure to the contaminant metal Nickel. Several time- and dose-dependent changes were highlighted, providing mechanistic insight into how these important model organisms handle Ni contamination.

  10. Serum metabolome and lipidome changes in adult patients with primary dengue infection.

    Directory of Open Access Journals (Sweden)

    Liang Cui

    Full Text Available Dengue virus (DENV is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44 across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive

  11. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism.

    Science.gov (United States)

    Gevi, Federica; Zolla, Lello; Gabriele, Stefano; Persico, Antonio M

    2016-01-01

    Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status. ASD-specific urinary metabolomic patterns were explored at an early age in 30 ASD children and 30 matched controls (age range 2-7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC and mass spectrometry, a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. Urinary metabolites displaying the largest differences between young ASD and control children belonged to the tryptophan and purine metabolic pathways. Also, vitamin B 6 , riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate and CoA, and pyrimidine metabolism differed significantly. ASD children preferentially transform tryptophan into xanthurenic acid and quinolinic acid (two catabolites of the kynurenine pathway), at the expense of kynurenic acid and especially of melatonin. Also, the gut microbiome contributes to altered tryptophan metabolism, yielding increased levels of indolyl 3-acetic acid and indolyl lactate. The metabolic pathways most distinctive of young Italian autistic children largely overlap with those found in rodent models of ASD following maternal immune activation or genetic manipulations. These results are consistent with the proposal of a purine-driven cell danger response, accompanied by overproduction of epileptogenic and

  12. Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension.

    Directory of Open Access Journals (Sweden)

    Timo P Hiltunen

    Full Text Available In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles.Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings.Amlodipine (P values down to 0.002, bisoprolol (P values down to 2 x 10-5 and losartan (P values down to 2 x 10-4 consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002 the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4 and urea cycle metabolites. Decreases of both systolic (P = 0.06 and diastolic (P = 0.04 blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation.Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.

  13. Metabolomic analysis of wild and transgenic Nicotiana langsdorffii plants exposed to abiotic stresses: unraveling metabolic responses.

    Science.gov (United States)

    Scalabrin, Elisa; Radaelli, Marta; Rizzato, Giovanni; Bogani, Patrizia; Buiatti, Marcello; Gambaro, Andrea; Capodaglio, Gabriele

    2015-08-01

    Nicotiana langsdorffii plants, wild and transgenic for the Agrobacterium rhizogenes rol C gene and the rat glucocorticoid receptor (GR) gene, were exposed to different abiotic stresses (high temperature, water deficit, and high chromium concentrations). An untargeted metabolomic analysis was carried out in order to investigate the metabolic effects of the inserted genes in response to the applied stresses and to obtain a comprehensive profiling of metabolites induced during abiotic stresses. High-performance liquid chromatography separation (HPLC) coupled to high-resolution mass spectrometry (HRMS) enabled the identification of more than 200 metabolites, and statistical analysis highlighted the most relevant compounds for each plant treatment. The plants exposed to heat stress showed a unique set of induced secondary metabolites, some of which were known while others were not previously reported for this kind of stress; significant changes were observed especially in lipid composition. The role of trichome, as a protection against heat stress, is here suggested by the induction of both acylsugars and glykoalkaloids. Water deficit and Cr(VI) stresses resulted mainly in enhanced antioxidant (HCAs, polyamine) levels and in the damage of lipids, probably as a consequence of reactive oxygen species (ROS) production. Moreover, the ability of rol C expression to prevent oxidative burst was confirmed. The results highlighted a clear influence of GR modification on plant stress response, especially to water deficiency-a phenomenon whose applications should be further investigated. This study provides new insights into the field of system biology and demonstrates the importance of metabolomics in the study of plant functioning. Graphical Abstract Untargeted metabolomic analysis was applied to wild type, GR and RolC modified Nicotiana Langsdorffii plants exposed to heat, water and Cr(VI) stresses. The key metabolites, highly affected by stress application, were identified

  14. QCScreen: a software tool for data quality control in LC-HRMS based metabolomics.

    Science.gov (United States)

    Simader, Alexandra Maria; Kluger, Bernhard; Neumann, Nora Katharina Nicole; Bueschl, Christoph; Lemmens, Marc; Lirk, Gerald; Krska, Rudolf; Schuhmacher, Rainer

    2015-10-24

    Metabolomics experiments often comprise large numbers of biological samples resulting in huge amounts of data. This data needs to be inspected for plausibility before data evaluation to detect putative sources of error e.g. retention time or mass accuracy shifts. Especially in liquid chromatography-high resolution mass spectrometry (LC-HRMS) based metabolomics research, proper quality control checks (e.g. for precision, signal drifts or offsets) are crucial prerequisites to achieve reliable and comparable results within and across experimental measurement sequences. Software tools can support this process. The software tool QCScreen was developed to offer a quick and easy data quality check of LC-HRMS derived data. It allows a flexible investigation and comparison of basic quality-related parameters within user-defined target features and the possibility to automatically evaluate multiple sample types within or across different measurement sequences in a short time. It offers a user-friendly interface that allows an easy selection of processing steps and parameter settings. The generated results include a coloured overview plot of data quality across all analysed samples and targets and, in addition, detailed illustrations of the stability and precision of the chromatographic separation, the mass accuracy and the detector sensitivity. The use of QCScreen is demonstrated with experimental data from metabolomics experiments using selected standard compounds in pure solvent. The application of the software identified problematic features, samples and analytical parameters and suggested which data files or compounds required closer manual inspection. QCScreen is an open source software tool which provides a useful basis for assessing the suitability of LC-HRMS data prior to time consuming, detailed data processing and subsequent statistical analysis. It accepts the generic mzXML format and thus can be used with many different LC-HRMS platforms to process both multiple

  15. Mitochondrial responses to extreme environments: insights from metabolomics.

    Science.gov (United States)

    O'Brien, Katie A; Griffin, Julian L; Murray, Andrew J; Edwards, Lindsay M

    2015-01-01

    Humans are capable of survival in a remarkable range of environments, including the extremes of temperature and altitude as well as zero gravity. Investigation into physiological function in response to such environmental stresses may help further our understanding of human (patho-) physiology both at a systems level and in certain disease states, making it a highly relevant field of study. This review focuses on the application of metabolomics in assessing acclimatisation to these states, particularly the insights this approach can provide into mitochondrial function. It includes an overview of metabolomics and the associated analytical tools and also suggests future avenues of research.

  16. Metabolome analysis - mass spectrometry and microbial primary metabolites

    DEFF Research Database (Denmark)

    Højer-Pedersen, Jesper Juul

    2008-01-01

    increased amounts of data generated in high resolution. One major limitation though is the digestion of data coverting the information into a format that can be interpreted in a biological context and take metabolomics beyond the principle of guilt-byassociation. To analyze the data there is a general need....... Statistical analysis of the footprinting data revealed discriminating ions, which could be assigned using the in silico metabolome. By this approach metabolic footprinting can advance from a classification method that is used to derive biological information based on guilt-by-association, to a tool...

  17. Metabolomic Biomarkers in the Progression to Type 1 Diabetes

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Kaur, Simranjeet; Pociot, Flemming

    2016-01-01

    Metabolomics is the snapshot of all detectable metabolites and lipids in biological materials and has potential in reflecting genetic and environmental factors contributing to the development of complex diseases, such as type 1 diabetes. The progression to seroconversion to development of type 1...... diabetes has been studied using this technique, although in relatively small cohorts and at limited time points. Overall, three observations have been consistently reported; phospholipids at birth are lower in children developing type 1 diabetes early in childhood, methionine levels are lower in children...... at seroconversion, and triglycerides are increased at seroconversion and associated to microbiome diversity, indicating an association between the metabolome and microbiome in type 1 diabetes progression....

  18. Metabolomics, Nutrition, and Potential Biomarkers of Food Quality, Intake, and Health Status.

    Science.gov (United States)

    Sébédio, Jean-Louis

    Diet, dietary patterns, and other environmental factors such as exposure to toxins are playing an important role in the prevention/development of many diseases, like obesity, type 2 diabetes, and consequently on the health status of individuals. A major challenge nowadays is to identify novel biomarkers to detect as early as possible metabolic dysfunction and to predict evolution of health status in order to refine nutritional advices to specific population groups. Omics technologies such as genomics, transcriptomics, proteomics, and metabolomics coupled with statistical and bioinformatics tools have already shown great potential in this research field even if so far only few biomarkers have been validated. For the past two decades, important analytical techniques have been developed to detect as many metabolites as possible in human biofluids such as urine, blood, and saliva. In the field of food science and nutrition, many studies have been carried out for food authenticity, quality, and safety, as well as for food processing. Furthermore, metabolomic investigations have been carried out to discover new early biomarkers of metabolic dysfunction and predictive biomarkers of developing pathologies (obesity, metabolic syndrome, type-2 diabetes, etc.). Great emphasis is also placed in the development of methodologies to identify and validate biomarkers of nutrients exposure. © 2017 Elsevier Inc. All rights reserved.

  19. Application of a Deep Neural Network to Metabolomics Studies and Its Performance in Determining Important Variables.

    Science.gov (United States)

    Date, Yasuhiro; Kikuchi, Jun

    2018-02-06

    Deep neural networks (DNNs), which are kinds of the machine learning approaches, are powerful tools for analyzing big sets of data derived from biological and environmental systems. However, DNNs are not applicable to metabolomics studies because they have difficulty in identifying contribution factors, e.g., biomarkers, in constructed classification and regression models. In this paper, we describe an improved DNN-based analytical approach that incorporates an importance estimation for each variable using a mean decrease accuracy (MDA) calculation, which is based on a permutation algorithm; this approach is called DNN-MDA. The performance of the DNN-MDA approach was evaluated using a data set of metabolic profiles derived from yellowfin goby that lived in various rivers throughout Japan. Its performance was compared with that of conventional multivariate and machine learning methods, and the DNN-MDA approach was found to have the best classification accuracy (97.8%) among the examined methods. In addition to this, the DNN-MDA approach facilitated the identification of important variables such as trimethylamine N-oxide, inosinic acid, and glycine, which were characteristic metabolites that contributed to the discrimination of the geographical differences between fish caught in the Kanto region and those caught in other regions. As a result, the DNN-MDA approach is a useful and powerful tool for determining the geographical origins of specimens and identifying their biomarkers in metabolomics studies that are conducted in biological and environmental systems.

  20. Metabolomic fingerprinting of saffron by LC/MS: novel authenticity markers.

    Science.gov (United States)

    Guijarro-Díez, Miguel; Nozal, Leonor; Marina, María Luisa; Crego, Antonio Luis

    2015-09-01

    An untargeted metabolomic approach using liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry was developed in this work to identify novel markers for saffron authenticity which is an important matter related to consumer protection, quality assurance, active properties, and also economical impact (saffron is the most expensive spice). Metabolic fingerprinting of authentic and suspicious saffron samples from different geographical origin was obtained and analyzed. Different extracting protocols and chromatographic methodologies were evaluated to obtain the most adequate extracting and separation conditions. Using an ethanol/water mixture at pH 9.0 and an elution gradient with a fused core C18 column enabled obtaining the highest number of significant components between authentic and adulterated saffron. By using multivariate statistical analysis, predictive classification models for authenticity and geographical origin were obtained. Moreover, 84 and 29 significant metabolites were detected as candidates for markers of authenticity and geographical origin, respectively, from which only 34 metabolites were tentatively identified as authenticity markers of saffron, but none related to its geographical origin. Six characteristic compounds of saffron (kaempferol 3-O-glucoside, kaempferol 3-O-sophoroside, kaempferol 3,7-O-diglucoside, kaempferol 3,7,4'-O-triglucoside, kaempferol 3-O-sophoroside-7-O-glucoside, and geranyl-O-glucoside) were confirmed by comparing experimental MS/MS fragmentation patterns with those provided in scientific literature being proposed as novel markers of authenticity. Graphical Abstract Metabolomic fingerprinting of saffron.

  1. Systematic analysis of the polyphenol metabolome using the Phenol‐Explorer database

    Science.gov (United States)

    Rothwell, Joseph A.; Urpi‐Sarda, Mireia; Boto‐Ordoñez, Maria; Llorach, Rafael; Farran‐Codina, Andreu; Barupal, Dinesh Kumar; Neveu, Vanessa; Manach, Claudine; Andres‐Lacueva, Cristina

    2016-01-01

    Scope The Phenol‐Explorer web database details 383 polyphenol metabolites identified in human and animal biofluids from 221 publications. Here, we exploit these data to characterize and visualize the polyphenol metabolome, the set of all metabolites derived from phenolic food components. Methods and results Qualitative and quantitative data on 383 polyphenol metabolites as described in 424 human and animal intervention studies were systematically analyzed. Of these metabolites, 301 were identified without prior enzymatic hydrolysis of biofluids, and included glucuronide and sulfate esters, glycosides, aglycones, and O‐methyl ethers. Around one‐third of these compounds are also known as food constituents and corresponded to polyphenols absorbed without further metabolism. Many ring‐cleavage metabolites formed by gut microbiota were noted, mostly derived from hydroxycinnamates, flavanols, and flavonols. Median maximum plasma concentrations (C max) of all human metabolites were 0.09 and 0.32 μM when consumed from foods or dietary supplements, respectively. Median time to reach maximum plasma concentration in humans (T max) was 2.18 h. Conclusion These data show the complexity of the polyphenol metabolome and the need to take into account biotransformations to understand in vivo bioactivities and the role of dietary polyphenols in health and disease. PMID:26310602

  2. Systematic analysis of the polyphenol metabolome using the Phenol-Explorer database.

    Science.gov (United States)

    Rothwell, Joseph A; Urpi-Sarda, Mireia; Boto-Ordoñez, Maria; Llorach, Rafael; Farran-Codina, Andreu; Barupal, Dinesh Kumar; Neveu, Vanessa; Manach, Claudine; Andres-Lacueva, Cristina; Scalbert, Augustin

    2016-01-01

    The Phenol-Explorer web database details 383 polyphenol metabolites identified in human and animal biofluids from 221 publications. Here, we exploit these data to characterize and visualize the polyphenol metabolome, the set of all metabolites derived from phenolic food components. Qualitative and quantitative data on 383 polyphenol metabolites as described in 424 human and animal intervention studies were systematically analyzed. Of these metabolites, 301 were identified without prior enzymatic hydrolysis of biofluids, and included glucuronide and sulfate esters, glycosides, aglycones, and O-methyl ethers. Around one-third of these compounds are also known as food constituents and corresponded to polyphenols absorbed without further metabolism. Many ring-cleavage metabolites formed by gut microbiota were noted, mostly derived from hydroxycinnamates, flavanols, and flavonols. Median maximum plasma concentrations (C(max)) of all human metabolites were 0.09 and 0.32 μM when consumed from foods or dietary supplements, respectively. Median time to reach maximum plasma concentration in humans (T(max)) was 2.18 h. These data show the complexity of the polyphenol metabolome and the need to take into account biotransformations to understand in vivo bioactivities and the role of dietary polyphenols in health and disease. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  4. Metabolomic Pathways to Osteoporosis in Middle-Aged Women: A Genome-Metabolome-Wide Mendelian Randomization Study.

    Science.gov (United States)

    Moayyeri, Alireza; Cheung, Ching-Lung; Tan, Kathryn Cb; Morris, John A; Cerani, Agustin; Mohney, Robert P; Richards, J Brent; Hammond, Christopher; Spector, Tim D; Menni, Cristina

    2017-12-12

    The metabolic state of the body can be a major determinant of bone health. We used a Mendelian randomization approach to identify metabolites causally associated with bone mass to better understand the biological mechanisms of osteoporosis. We tested bone phenotypes (femoral neck, total hip, and lumbar spine bone mineral density [BMD]) for association with 280 fasting blood metabolites in 6055 women from TwinsUK cohort with genomewide genotyping scans. Causal associations between metabolites and bone phenotypes were further assessed in a bidirectional Mendelian randomization study using genetic markers/scores as instrumental variables. Significant associations were replicated in 624 participants from the Hong Kong Osteoporosis Study (HKOS). Fifteen metabolites showed direct associations with bone phenotypes after adjusting for covariates and multiple testing. Using genetic instruments, four of these metabolites were found to be causally associated with hip or spine BMD. These included androsterone sulfate, epiandrosterone sulfate, 5alpha-androstan-3beta17beta-diol disulfate (encoded by CYP3A5), and 4-androsten-3beta17beta-diol disulfate (encoded by SULT2A1). In the HKOS population, all four metabolites showed significant associations with hip and spine BMD in the expected directions. No causal reverse association between BMD and any of the metabolites were found. In the first metabolome-genomewide Mendelian randomization study of human bone mineral density, we identified four novel biomarkers causally associated with BMD. Our findings reveal novel biological pathways involved in the pathogenesis of osteoporosis. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  5. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2014-11-21

    The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.

  6. Oral histoplasmosis

    Directory of Open Access Journals (Sweden)

    Patil Karthikeya

    2009-01-01

    Full Text Available Histoplasmosis is a systemic fungal disease that takes various clinical forms, among which oral lesions are rare. The disseminated form of the disease that usually occurs in association with Human Immunodeficiency Virus (HIV is one of the AIDS-defining diseases. Isolated oral histoplasmosis, without systemic involvement, with underlying immunosuppression due to AIDS is very rare. We report one such case of isolated oral histoplasmosis in a HIV-infected patient.

  7. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  8. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    International Nuclear Information System (INIS)

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Kim, Kyu-Bong; Kim, Seon Hwa; Choi, Ki Hwan; Lee, Hwa Jeong

    2012-01-01

    Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1 H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg −1 ) or co-administration with cimetidine (100 mg kg −1 ), which protects against GI damage. The 1 H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg −1 ) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

  9. Serum and Brain Metabolomic Variations Reveal Perturbation of Sleep Deprivation on Rats and Ameliorate Effect of Total Ginsenoside Treatment

    Directory of Open Access Journals (Sweden)

    Xiao-jun Gou

    2017-01-01

    Full Text Available Sleep loss or sleep deprivation (SD refers to shorter sleep than average baseline need, and SD has been a serious problem of modern societies which affects health and well-being. Panax ginseng is a well-known traditional Chinese medicine (TCM. Our previous study has demonstrated that total ginsenosides (GS, the extracts from Panax ginseng, could effectively improve cognition and behavior on SD rats. However, little is known about its metabolomic study. In this study, serum and brain metabolomic method based on gas chromatography coupled with mass spectrometry (GC/MS was employed to evaluate the efficacy and study the mechanism of GS on a rat model of SD. With pattern recognition analysis of serum and brain tissue metabolite profile, a clear separation of the model group and control group was acquired for serum and brain tissue samples; the MGS (model + GS group showed a tendency of recovering when compared to control group, which was consistent with behavioral and biochemical parameters. 39 and 40 potential biomarkers of brain tissues and serum samples, respectively, were identified and employed to explore the possible mechanism. Our work revealed that GS has significant protective effects on SD, and metabolomics is a useful tool for evaluating efficacy and elucidating mechanism in TCM.

  10. Metabolomic approach for discrimination of processed ginseng genus (Panax ginseng and Panax quinquefolius) using UPLC-QTOF MS

    Science.gov (United States)

    Park, Hee-Won; In, Gyo; Kim, Jeong-Han; Cho, Byung-Goo; Han, Gyeong-Ho; Chang, Il-Moo

    2013-01-01

    Discriminating between two herbal medicines (Panax ginseng and Panax quinquefolius), with similar chemical and physical properties but different therapeutic effects, is a very serious and difficult problem. Differentiation between two processed ginseng genera is even more difficult because the characteristics of their appearance are very similar. An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS)-based metabolomic technique was applied for the metabolite profiling of 40 processed P. ginseng and processed P. quinquefolius. Currently known biomarkers such as ginsenoside Rf and F11 have been used for the analysis using the UPLC-photodiode array detector. However, this method was not able to fully discriminate between the two processed ginseng genera. Thus, an optimized UPLC-QTOF-based metabolic profiling method was adapted for the analysis and evaluation of two processed ginseng genera. As a result, all known biomarkers were identified by the proposed metabolomics, and additional potential biomarkers were extracted from the huge amounts of global analysis data. Therefore, it is expected that such metabolomics techniques would be widely applied to the ginseng research field. PMID:24558312

  11. Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A

    Science.gov (United States)

    Ye, Guozhu; Chen, Yajie; Wang, Hong-Ou; Ye, Ting; Lin, Yi; Huang, Qiansheng; Chi, Yulang; Dong, Sijun

    2016-10-01

    Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA. Unexpectedly, we observed enhanced neural activity accompanied by lactate accumulation and accelerated heart rates due to an increase in dopamine pathway and a decrease in inhibitory neurotransmitters following H-BPA exposure. Notably, disorders of the neural system, and disruptions in glycolysis, the TCA cycle, nucleoside metabolism, lipid metabolism, glutamate and aspartate metabolism induced by H-BPA exposure were heritable. Furthermore, lactate and dopa were identified as potential biomarkers of the developmental toxicity of H-BPA and related genetic effects. This study has demonstrated that the metabolomics approach is a useful tool for obtaining comprehensive and novel insights into the molecular developmental toxicity of environmental pollutants.

  12. Metabolomic approach for discrimination of processed ginseng genus (Panax ginseng and Panax quinquefolius using UPLC-QTOF MS

    Directory of Open Access Journals (Sweden)

    Hee-Won Park

    2014-01-01

    Full Text Available Discriminating between two herbal medicines (Panax ginseng and Panax quinquefolius, with similar chemical and physical properties but different therapeutic effects, is a very serious and difficult problem. Differentiation between two processed ginseng genera is even more difficult because the characteristics of their appearance are very similar. An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS-based metabolomic technique was applied for the metabolite profiling of 40 processed P. ginseng and processed P. quinquefolius. Currently known biomarkers such as ginsenoside Rf and F11 have been used for the analysis using the UPLC-photodiode array detector. However, this method was not able to fully discriminate between the two processed ginseng genera. Thus, an optimized UPLC-QTOF-based metabolic profiling method was adapted for the analysis and evaluation of two processed ginseng genera. As a result, all known biomarkers were identified by the proposed metabolomics, and additional potential biomarkers were extracted from the huge amounts of global analysis data. Therefore, it is expected that such metabolomics techniques would be widely applied to the ginseng research field.

  13. Metabolic Effect of Dietary Taurine Supplementation on Nile Tilapia (Oreochromis nilotictus) Evaluated by NMR-Based Metabolomics.

    Science.gov (United States)

    Shen, Guiping; Huang, Ying; Dong, Jiyang; Wang, Xuexi; Cheng, Kian-Kai; Feng, Jianghua; Xu, Jingjing; Ye, Jidan

    2018-01-10

    Taurine is indispensable in aquatic diets that are based solely on plant protein, and it promotes growth of many fish species. However, the physiological and metabolome effects of taurine on fish have not been well described. In this study, 1 H NMR-based metabolomics approaches were applied to investigate the metabolite variations in Nile tilapia (Oreochromis nilotictus) muscle in order to visualize the metabolic trajectory and reveal the possible mechanisms of metabolic effects of dietary taurine supplementation on tilapia growth. After extraction using aqueous and organic solvents, 19 taurine-induced metabolic changes were evaluated in our study. The metabolic changes were characterized by differences in carbohydrate, amino acid, lipid, and nucleotide contents. The results indicate that taurine supplementation could significantly regulate the physiological state of fish and promote growth and development. These results provide a basis for understanding the mechanism of dietary taurine supplementation in fish feeding. 1 H NMR spectroscopy, coupled with multivariate pattern recognition technologies, is an efficient and useful tool to map the fish metabolome and identify metabolic responses to different dietary nutrients in aquaculture.

  14. Metabolomic approach for discrimination of processed ginseng genus (Panax ginseng and Panax quinquefolius) using UPLC-QTOF MS.

    Science.gov (United States)

    Park, Hee-Won; In, Gyo; Kim, Jeong-Han; Cho, Byung-Goo; Han, Gyeong-Ho; Chang, Il-Moo

    2014-01-01

    Discriminating between two herbal medicines (Panax ginseng and Panax quinquefolius), with similar chemical and physical properties but different therapeutic effects, is a very serious and difficult problem. Differentiation between two processed ginseng genera is even more difficult because the characteristics of their appearance are very similar. An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS)-based metabolomic technique was applied for the metabolite profiling of 40 processed P. ginseng and processed P. quinquefolius. Currently known biomarkers such as ginsenoside Rf and F11 have been used for the analysis using the UPLC-photodiode array detector. However, this method was not able to fully discriminate between the two processed ginseng genera. Thus, an optimized UPLC-QTOF-based metabolic profiling method was adapted for the analysis and evaluation of two processed ginseng genera. As a result, all known biomarkers were identified by the proposed metabolomics, and additional potential biomarkers were extracted from the huge amounts of global analysis data. Therefore, it is expected that such metabolomics techniques would be widely applied to the ginseng research field.

  15. Metabolomic insights into the intricate gut microbial–host interaction in the development of obesity and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Magali ePalau-Rodriguez

    2015-10-01

    Full Text Available Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbial-host co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e. niacin, purines and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbial-host crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders.

  16. Elucidating causes of Diporeia decline in the Great Lakes via metabolomics: physiological responses after exposure to different stressors.

    Science.gov (United States)

    Maity, Suman; Jannasch, Amber; Adamec, Jiri; Watkins, James M; Nalepa, Thomas; Höök, Tomas O; Sepúlveda, Maria S

    2013-01-01

    The benthic macroinvertebrate Diporeia spp. have been extirpated from many areas of the Laurentian Great Lakes, but the mechanisms underlying such declines are not fully understood. Diporeia declines coinciding with the invasion of exotic dreissenid mussels (zebra and quagga) have led to the hypothesis that Diporeia declines are a result of decreased food availability from increasing competition with dreissenids for diatoms. There is additional evidence that Diporeia are negatively affected when in close proximity to dreissenids, probably because of exposure to toxins present in the mussels' pseudofeces. Diporeia are also known to be sensitive to anthropogenic contaminants (such as polychlorinated biphenyls [PCBs]) present in Great Lakes sediments. To better understand the physiological responses of Diporeia to diverse stressors, we conducted three 28-d experiments evaluating changes in the metabolomes of Diporeia (1) fed diatoms (Cyclotella meneghiniana) versus starved, (2) exposed (from Lake Michigan and Cayuga Lake) to quagga mussels (Dreissena bugensis), and (3) exposed to sediments contaminated with PCBs. The metabolomes of samples were examined using both two-dimensional gas and liquid chromatography coupled with mass spectrometry. Each stressor elicited a unique metabolome response characterized by enhanced citric acid cycle, fatty acid biosynthesis, and protein metabolism in diatom-fed Diporeia; impaired glycolysis, protein catabolism, and folate metabolism in Diporeia from Lake Michigan irrespective of quagga mussel exposure, suggesting lake-specific adaptation mechanisms; and altered cysteine and phospholipid metabolism during PCB exposure. Subsequent comparisons of these stressor-specific metabolic responses with metabolomes of a feral Diporeia population would help identify stressors affecting Diporeia populations throughout the Great Lakes.

  17. The combination of four analytical methods to explore skeletal muscle metabolomics: Better coverage of metabolic pathways or a marketing argument?

    Science.gov (United States)

    Bruno, C; Patin, F; Bocca, C; Nadal-Desbarats, L; Bonnier, F; Rey