PubMed

Related Articles Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery. Genes Nutr. 2018;13:3 Authors: Praticò G, Gao Q, Scalbert A, Vergères G, Kolehmainen M, Manach C, Brennan L, Pedapati SH, Afman LA, Wishart DS, Vázquez-Fresno R, Lacueva CA, Garcia-Aloy M, Verhagen H, Feskens EJM, Dragsted LO Abstract Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health. PMID: 29484030 [PubMed]

Related Articles Antibiotic growth promoters virginiamycin and bacitracin methylene disalicylate alter the chicken intestinal metabolome. Sci Rep. 2018 Feb 26;8(1):3592 Authors: Gadde UD, Oh S, Lillehoj HS, Lillehoj EP Abstract Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N6-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics. PMID: 29483631 [PubMed - in process]

Related Articles Elastic net regularized regression for time-series analysis of plasma metabolome stability under sub-optimal freezing condition. Sci Rep. 2018 Feb 26;8(1):3659 Authors: Gonzales GB, De Saeger S Abstract In this paper, the stability of the plasma metabolome at -20 °C for up to 30 days was evaluated using liquid chromatography-high resolution mass spectrometric metabolomics analysis. To follow the time-series deterioration of the plasma metabolome, the use of an elastic net regularized regression model for the prediction of storage time at -20 °C based on the plasma metabolomic profile, and the selection and ranking of metabolites with high temporal changes was demonstrated using the glmnet package in R. Out of 1229 (positive mode) and 1483 (negative mode) metabolite features, the elastic net model extracted 32 metabolites of interest in both positive and negative modes. L-gamma-glutamyl-L-(iso)leucine (tentative identification) was found to have the highest time-dependent change and significantly increased proportionally to the storage time of plasma at -20 °C (R2 = 0.6378 [positive mode], R2 = 0.7893 [negative mode], p-value < 0.00001). Based on the temporal profiles of the extracted metabolites by the model, results show only minimal deterioration of the plasma metabolome at -20 °C up to 1 month. However, majority of the changes appeared at around 12-15 days of storage. This allows scientists to better plan logistics and storage strategies for samples obtained from low-resource settings, where -80 °C storage is not guaranteed. PMID: 29483546 [PubMed - in process]

Related Articles Lkb1 deficiency confers glutamine dependency in polycystic kidney disease. Nat Commun. 2018 Feb 26;9(1):814 Authors: Flowers EM, Sudderth J, Zacharias L, Mernaugh G, Zent R, DeBerardinis RJ, Carroll TJ Abstract Polycystic kidney disease (PKD) is a common genetic disorder characterized by the growth of fluid-filled cysts in the kidneys. Several studies reported that the serine-threonine kinase Lkb1 is dysregulated in PKD. Here we show that genetic ablation of Lkb1 in the embryonic ureteric bud has no effects on tubule formation, maintenance, or growth. However, co-ablation of Lkb1 and Tsc1, an mTOR repressor, results in an early developing, aggressive form of PKD. We find that both loss of Lkb1 and loss of Pkd1 render cells dependent on glutamine for growth. Metabolomics analysis suggests that Lkb1 mutant kidneys require glutamine for non-essential amino acid and glutathione metabolism. Inhibition of glutamine metabolism in both Lkb1/Tsc1 and Pkd1 mutant mice significantly reduces cyst progression. Thus, we identify a role for Lkb1 in glutamine metabolism within the kidney epithelia and suggest that drugs targeting glutamine metabolism may help reduce cyst number and/or size in PKD. PMID: 29483507 [PubMed - in process]

Related Articles Deletion of the neural tube defect-associated gene Mthfd1l disrupts one-carbon and central energy metabolism in mouse embryos. J Biol Chem. 2018 Feb 26;: Authors: Bryant JD, Sweeney SR, Sentandreu E, Shin M, Ipas H, Xhemalce B, Momb J, Tiziani S, Appling DR Abstract One-carbon (1C) metabolism is a universal folate-dependent pathway essential for de novo purine and thymidylate synthesis, amino acid interconversion, universal methyl-donor production, and regeneration of redox cofactors. Homozygous deletion of the 1C pathway gene Mthfd1l encoding methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like, which catalyzes mitochondrial formate production from 10-formyltetrahydrofolate, results in 100% penetrant embryonic neural tube defects (NTDs), underscoring the central role of mitochondrially derived formate in embryonic development and providing a mechanistic link between folate and NTDs. However, the specific metabolic processes that are perturbed by Mthfd1l deletion are not known. Here, we performed untargeted metabolomics on whole Mthfd1l-null and wild-type mouse embryos in combination with isotope tracer analysis in mouse embryonic fibroblast (MEF) cell lines to identify Mthfd1l deletion-induced disruptions in 1C metabolism, glycolysis, and the TCA cycle. We found that maternal formate supplementation largely corrects these disruptions in Mthfd1l-null embryos. Serine tracer experiments revealed that Mthfd1l-null MEFs have altered methionine synthesis, indicating that Mthfd1l deletion impairs the methyl cycle. Supplementation of Mthfd1l-null MEFs with formate, hypoxanthine, or combined hypoxanthine and thymidine restored their growth to wild-type levels. Thymidine addition alone was ineffective, suggesting a purine synthesis defect in Mthfd1l-null MEFs. Tracer experiments also revealed lower proportions of labeled hypoxanthine and inosine monophosphate in Mthfd1l-null than in wild-type MEFs, suggesting that Mthfd1l deletion results in increased reliance on the purine salvage pathway. These results indicate that disruptions of mitochondrial 1C metabolism have wide-ranging consequences for many metabolic processes, including those that may not directly interact with 1C metabolism. PMID: 29483189 [PubMed - as supplied by publisher]

Related Articles Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes. J Biol Chem. 2018 Feb 26;: Authors: Bruegger JJ, Smith BC, Wynia-Smith SL, Marletta MA Abstract Cysteine S-nitrosation is a reversible posttranslational modification mediated by nitric oxide (·NO)-derived agents. S-nitrosation participates in cellular signaling and is associated with several diseases such as cancer, cardiovascular diseases, and neuronal disorders. Despite the physiological importance of this nonclassical ·NO signaling pathway, little is understood about how much S-nitrosation affects protein function. Moreover, identifying physiologically relevant targets of S-nitrosation is difficult because of the dynamics of transnitrosation and a limited understanding of the physiological mechanisms leading to selective protein S-nitrosation. To identify proteins whose activities are modulated by S-nitrosation, we performed a metabolomics study comparing wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. We integrated our results with those of a previous proteomics study that identified physiologically relevant S-nitrosated cysteines, and we found that the activity of at least 21 metabolic enzymes might be regulated by S-nitrosation. We cloned, expressed, and purified four of these enzymes and observed that S-nitrosation inhibits the metabolic enzymes 6-phosphogluconate dehydrogenase (6PGD), Δ1- pyrroline-5-carboxylate dehydrogenase (ALDH4A1), catechol-O-methyltransferase (COMT), and D-3-phosphoglycerate dehydrogenase (PHGDH). Furthermore, using site-directed mutagenesis, we identified the predominate cysteine residue influencing the observed activity changes in each enzyme.In summary, using an integrated metabolomics approach, we have identified several physiologically relevant S-nitrosation targets, including metabolic enzymes, which are inhibited by this modification, and have found the cysteines modified by S-nitrosation in each enzyme. PMID: 29483187 [PubMed - as supplied by publisher]

Related Articles The nephrologist of tomorrow: towards a kidney-omic future. Pediatr Nephrol. 2017 Mar;32(3):393-404 Authors: Hanna MH, Dalla Gassa A, Mayer G, Zaza G, Brophy PD, Gesualdo L, Pesce F Abstract Omics refers to the collective technologies used to explore the roles and relationships of the various types of molecules that make up the phenotype of an organism. Systems biology is a scientific discipline that endeavours to quantify all of the molecular elements of a biological system. Therefore, it reflects the knowledge acquired by omics in a meaningful manner by providing insights into functional pathways and regulatory networks underlying different diseases. The recent advances in biotechnological platforms and statistical tools to analyse such complex data have enabled scientists to connect the experimentally observed correlations to the underlying biochemical and pathological processes. We discuss in this review the current knowledge of different omics technologies in kidney diseases, specifically in the field of pediatric nephrology, including biomarker discovery, defining as yet unrecognized biologic therapeutic targets and linking omics to relevant standard indices and clinical outcomes. We also provide here a unique perspective on the field, taking advantage of the experience gained by the large-scale European research initiative called "Systems Biology towards Novel Chronic Kidney Disease Diagnosis and Treatment" (SysKid). Based on the integrative framework of Systems biology, SysKid demonstrated how omics are powerful yet complex tools to unravel the consequences of diabetes and hypertension on kidney function. PMID: 26961492 [PubMed - indexed for MEDLINE]

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/02/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Common bean varieties demonstrate differential physiological and metabolic responses to the pathogenic fungus Sclerotinia sclerotiorum. Plant Cell Environ. 2018 Feb 24;: Authors: Robison FM, Turner M, Jahn CE, Schwartz HF, Prenni JE, Brick MA, Heuberger AL Abstract Plant physiology and metabolism are important components of a plant response to microbial pathogens. Physiological resistance of common bean (Phaseolus vulgaris L.) to the fungal pathogen Sclerotinia sclerotiorum has been established, but the mechanisms of resistance are largely unknown. Here, the physiological and metabolic responses of bean varieties that differ in physiological resistance to S. sclerotiorum are investigated. Upon infection, the resistant bean variety A195 had a unique physiological response that included reduced photosynthesis and maintaining a higher leaf surface pH during infection. Leaf metabolomics was performed on healthy tissue adjacent to the necrotic lesion at 16, 24, and 48 hours post inoculation, and 144 metabolites were detected that varied between A195 and Sacramento following infection. The metabolites that varied in leaves included amines/amino acids, organic acids, phytoalexins, and ureides. The metabolic pathways associated with resistance included: amine metabolism, uriede-based nitrogen remobilization, antioxidant production, and bean-specific phytoalexin production. A second experiment was conducted in stems of 13 bean genotypes with varying resistance. Stem resistance was associated with phytoalexin production, but unlike leaf metabolism, lipid changes were associated with susceptibility. Taken together, the data supports a multi-faceted, physio-metabolic response of common bean to S. sclerotiorum that mediates resistance. PMID: 29476531 [PubMed - as supplied by publisher]

MCEE: a data preprocessing approach for metabolic confounding effect elimination. Anal Bioanal Chem. 2018 Feb 24;: Authors: Li Y, Li M, Jia W, Ni Y, Chen T Abstract It is well recognized that physiological and environmental factors such as race, age, gender, and diurnal cycles often have a definite influence on metabolic results that statistically manifests as confounding variables. Currently, removal or controlling of confounding effects relies heavily on experimental design. There are no available data processing techniques focusing on the compensation of their effects. We therefore proposed a new method, Metabolic confounding effect elimination (MCEE), to remove the influence of specified confounding factors and make the data more accurate. The method consists of three steps: metabolites grouping, confounder-related metabolites selection, and metabolites modification. Its effectiveness and advantages were evaluated comprehensively by several simulated models and real datasets, and were compared with two typical methods, the principal component analysis (PCA)- and the direct orthogonal signal correction (DOSC)-based methods. MCEE is simple, effective, and safe, and is independent of sample number, association degree, and missing value. Hence, it may serve as a good complement to existing metabolomics data preprocessing methods and aid in better understanding the metabolic and biological status of interest. Graphical Abstract Processing flow and demo performance of MCEE to Algorithm flow and demo performance of MCEE. PMID: 29476235 [PubMed - as supplied by publisher]

The autophagic network and cancer. Nat Cell Biol. 2018 Mar;20(3):243-251 Authors: Rybstein MD, Bravo-San Pedro JM, Kroemer G, Galluzzi L Abstract Mammalian cells harness autophagy to eliminate physiological byproducts of metabolism and cope with microenvironmental perturbations. Moreover, autophagy connects cellular adaptation with extracellular circuitries that impinge on immunity and metabolism. As it links transformed and non-transformed components of the tumour microenvironment, such an autophagic network is important for cancer initiation, progression and response to therapy. Here, we discuss the mechanisms whereby the autophagic network interfaces with multiple aspects of malignant disease. PMID: 29476153 [PubMed - in process]

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/02/24PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Changes in Metabolites Present in Lung Lining Fluid Following Exposure of Humans to Ozone. Toxicol Sci. 2018 Feb 19;: Authors: Cheng W, Duncan KE, Ghio AJ, Ward-Caviness C, Karoly ED, Diaz-Sanchez D, Conolly RB, Devlin RB Abstract Controlled human exposure to the oxidant air pollutant ozone causes decrements in lung function and increased inflammation as evidenced by neutrophil influx into the lung and increased levels of proinflammatory cytokines in the airways. Here we describe a targeted metabolomics evaluation of human bronchioalveolar lavage fluid (BALF) following controlled in vivo exposure to ozone to gain greater insight into its pulmonary effects. In a two-arm cross-over study, each healthy adult human volunteer was randomly exposed to filtered air (FA) and to 0.3 ppm ozone for 2 hr while undergoing intermittent exercise with a minimum of 4 weeks between exposures. Bronchoscopy was performed and BALF obtained at 1 (n = 9) or 24 (n = 23) h post-exposure. Metabolites were detected using ultrahigh performance liquid chromatography-tandem mass spectroscopy. At 1-hour post-exposure, a total of 28 metabolites were differentially expressed (DE) (p < 0.05) following ozone exposure compared to FA-exposure. These changes were associated with increased glycolysis and antioxidant responses, suggesting a rapid increased energy utilization as part of the cellular response to oxidative stress. At 24-hour post-exposure, 41 metabolites were DE. Many of the changes were in amino acids and linked with enhanced proteolysis. Changes associated with increased lipid membrane turnover were also observed. These later-stage changes were consistent with ongoing repair of airway tissues. There were 1.37 times as many metabolites were differentially expressed at 24 hour compared to 1-hour post-exposure. The changes at 1 hour reflect responses to oxidative stress while the changes at 24 hour indicate a broader set of responses consistent with tissue repair. These results illustrate the ability of metabolomic analysis to identify mechanistic features of ozone toxicity and aspects of the subsequent tissue response. PMID: 29471466 [PubMed - as supplied by publisher]

Mucosal and Systemic Responses of Immunogenic Vaccines Candidates against enteric Escherichia coli infections in ruminants: A review. Microb Pathog. 2018 Feb 19;: Authors: Lawan A, Jesse FFA, Idris UH, Odhah MN, Arsalan M, Muhammad NA, Bhutto KR, Damudu Peter I, Abraham GA, Wahid AH, Mohd-Azmi ML, Zamri-Saad M Abstract Innumerable Escherichia coli of animal origin are identified, which are of economic significance, likewise, cattle, sheep and goats are the carrier of enterohaemorrhagic E. coli, which are less pathogenic, and can spread to people by way of direct contact and through the contamination of foodstuff or portable drinking water, causing serious illness. The immunization of ruminants has been carried out for ages and is largely acknowledged as the most economical and maintainable process of monitoring E. coli infection in ruminants. Yet, only a limited number of E. coli vaccines are obtainable. Mucosal surfaces are the most important ingress for E. coli and thus mucosal immune responses function as the primary means of fortification. Largely contemporary vaccination processes are done by parenteral administration and merely limited number of E. coli vaccines are inoculated via mucosal itinerary, due to its decreased efficacy. Nevertheless, aiming at maximal mucosal partitions to stimulate defensive immunity at both mucosal compartments and systemic site epitomises a prodigious task. Enormous determinations are involved in order to improve on novel mucosal E. coli vaccines candidate by choosing apposite antigens with potent immunogenicity, manipulating novel mucosal itineraries of inoculation and choosing immune-inducing adjuvants. The target of E. coli mucosal vaccines is to stimulate a comprehensive, effective and defensive immunity by specifically counteracting the antibodies at mucosal linings and by the stimulation of cellular immunity. Furthermore, effective E. coli mucosal vaccine would make vaccination measures stress-free and appropriate for large number of inoculation. On account of contemporary advancement in proteomics, metagenomics, metabolomics and transcriptomics research, a comprehensive appraisal of the immeasurable genes and proteins that were divulged by a bacterium is now in easy reach. Moreover, there exist marvellous prospects in this bourgeoning technologies in comprehending the host bacteria affiliation. Accordingly, the flourishing knowledge could massively guarantee to the progression of immunogenic vaccines against E. coli infections in both humans and animals. This review highlight and expounds on the current prominence of mucosal and systemic immunogenic vaccines for the prevention of E. coli infections in ruminants. PMID: 29471137 [PubMed - as supplied by publisher]

A urinary biosignature for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS). Mitochondrion. 2018 Feb 19;: Authors: Esterhuizen K, Zander Lindeque J, Mason S, van der Westhuizen FH, Suomalainen A, Hakonen AH, Carroll CJ, Rodenburg RJ, de Laat PB, Janssen MCH, Smeitink JAM, Louw R Abstract We used a comprehensive metabolomics approach to study the altered urinary metabolome of two mitochondrial myopathy, encephalopathy lactic acidosis and stroke like episodes (MELAS) cohorts carrying the m.3243A>G mutation. The first cohort were used in an exploratory phase, identifying 36 metabolites that were significantly perturbed by the disease. During the second phase, the 36 selected metabolites were able to separate a validation cohort of MELAS patients completely from their respective control group, suggesting usefulness of these 36 markers as a diagnostic set. Many of the 36 perturbed metabolites could be linked to an altered redox state, fatty acid catabolism and one-carbon metabolism. However, our evidence indicates that, of all the metabolic perturbations caused by MELAS, stalled fatty acid oxidation prevailed as being particularly disturbed. The strength of our study was the utilization of five different analytical platforms to generate the robust metabolomics data reported here. We show that urine may be a useful source for disease-specific metabolomics data, linking, amongst others, altered one-carbon metabolism to MELAS. The results reported here are important in our understanding of MELAS and might lead to better treatment options for the disease. PMID: 29471047 [PubMed - as supplied by publisher]

Arctic, Antarctic, and temperate green algae Zygnema spp. under UV-B stress: vegetative cells perform better than pre-akinetes. Protoplasma. 2018 Feb 22;: Authors: Holzinger A, Albert A, Aigner S, Uhl J, Schmitt-Kopplin P, Trumhová K, Pichrtová M Abstract Species of Zygnema form macroscopically visible mats in polar and temperate terrestrial habitats, where they are exposed to environmental stresses. Three previously characterized isolates (Arctic Zygnema sp. B, Antarctic Zygnema sp. C, and temperate Zygnema sp. S) were tested for their tolerance to experimental UV radiation. Samples of young vegetative cells (1 month old) and pre-akinetes (6 months old) were exposed to photosynthetically active radiation (PAR, 400-700 nm, 400 μmol photons m-2 s-1) in combination with experimental UV-A (315-400 nm, 5.7 W m-2, no UV-B), designated as PA, or UV-A (10.1 W m-2) + UV-B (280-315 nm, 1.0 W m-2), designated as PAB. The experimental period lasted for 74 h; the radiation period was 16 h PAR/UV-A per day, or with additional UV-B for 14 h per day. The effective quantum yield, generally lower in pre-akinetes, was mostly reduced during the UV treatment, and recovery was significantly higher in young vegetative cells vs. pre-akinetes during the experiment. Analysis of the deepoxidation state of the xanthophyll-cycle pigments revealed a statistically significant (p < 0.05) increase in Zygnema spp. C and S. The content of UV-absorbing phenolic compounds was significantly higher (p < 0.05) in young vegetative cells compared to pre-akinetes. In young vegetative Zygnema sp. S, these phenolic compounds significantly increased (p < 0.05) upon PA and PAB. Transmission electron microscopy showed an intact ultrastructure with massive starch accumulations at the pyrenoids under PA and PAB. A possible increase in electron-dense bodies in PAB-treated cells and the occurrence of cubic membranes in the chloroplasts are likely protection strategies. Metabolite profiling by non-targeted RP-UHPLC-qToF-MS allowed a clear separation of the strains, but could not detect changes due to the PA and PAB treatments. Six hundred seventeen distinct molecular masses were detected, of which around 200 could be annotated from databases. These results indicate that young vegetative cells can adapt better to the experimental UV-B stress than pre-akinetes. PMID: 29470709 [PubMed - as supplied by publisher]

Metabolomics in Plant Stress Physiology. Adv Biochem Eng Biotechnol. 2018 Feb 23;: Authors: Ghatak A, Chaturvedi P, Weckwerth W Abstract Metabolomics is an essential technology for functional genomics and systems biology. It plays a key role in functional annotation of genes and understanding towards cellular and molecular, biotic and abiotic stress responses. Different analytical techniques are used to extend the coverage of a full metabolome. The commonly used techniques are NMR, CE-MS, LC-MS, and GC-MS. The choice of a suitable technique depends on the speed, sensitivity, and accuracy. This chapter provides insight into plant metabolomic techniques, databases used in the analysis, data mining and processing, compound identification, and limitations in metabolomics. It also describes the workflow of measuring metabolites in plants. Metabolomic studies in plant responses to stress are a key research topic in many laboratories worldwide. We summarize different approaches and provide a generic overview of stress responsive metabolite markers and processes compiled from a broad range of different studies. Graphical Abstract. PMID: 29470599 [PubMed - as supplied by publisher]

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites. Metabolites. 2018 Feb 22;8(1): Authors: Zhang B, Hu S, Baskin E, Patt A, Siddiqui JK, Mathé EA Abstract The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be checked multiple times a year and RaMP will be updated accordingly. PMID: 29470400 [PubMed]

Plant-derived polyphenols in human health: biological activity, metabolites and putative molecular targets. Curr Drug Metab. 2018 Feb 19;: Authors: Olivares-Vicente M, Barrajon-Catalan E, Herranz-Lopez M, Segura-Carretero A, Joven J, Encinar JA, Micol V Abstract Edible plants such as Hibiscus sabdariffa, Lippia citriodora, Rosmarinus officinalis and Olea europaea, are rich in bioactive compounds that represent most of the phenolic compounds families and have exhibited potential benefits in human health. These plants have been commonly used in folk medicine for their potential therapeutic properties in human chronic diseases. Recent evidence on these plants leads to postulate that polyphenols may account for such effects. Nevertheless, the compounds or metabolites that are responsible for reaching the molecular targets are still unknown. Data based on studies that directly use complex extracts on cellular models, without considering metabolic aspects, have limited applicability. In contrast, studies exploring the absorption process, metabolites in the blood circulation and tissues have become essential to identify the intracellular final effectors that are responsible for extracts bioactivity. Once the cellular metabolites are identified, computational molecular docking techniques suppose a unique tool for virtually screening a large number of compounds on selected protein targets in order to elucidate their potential mechanisms. In this review, we provide an updated overview of the in vitro and in vivo studies on the toxicity, absorption, permeability, pharmacokinetics and cellular metabolism of bioactive compounds derived from the abovementioned plants to identify the potential compounds that are responsible for the observed health effects. We also propose the use of in silico studies to virtually screen metabolites on selected protein targets, in combination with targeted metabolomics with high resolution mass spectrometry and using the candidate metabolites in cellular models, as the method of choice for elucidating the molecular mechanisms of these compounds.  . PMID: 29468962 [PubMed - as supplied by publisher]

Related Articles Urinary Metabolomics Profiles Associated to Bovine Meat Ingestion in Humans. Mol Nutr Food Res. 2018 Feb 22;: Authors: Khodorova NV, Rutledge DN, Oberli M, Mathiron D, Marcelo P, Benamouzig R, Tomé D, Gaudichon C, Pilard S Abstract SCOPE: The impact of meat consumption on human health is widely examined in nutritional epidemiological studies, especially due to the connexion between the consumption of red and processed meat and the risk of colon cancer. Food questionnaires do not assess the exposure to different methods of meat cooking. This study aimed to identify biomarkers of the acute ingestion of bovine meat cooked with 2 different processes. METHODS AND RESULTS: Non-targeted UPLC-MS metabolite profiling was done on urine samples obtained from 24 healthy volunteers before and 8h after the ingestion of a single meal composed of intrinsically 15 N labelled bovine meat, either cooked at 55 °C for 5 min or at 90 °C for 30 min. A Discriminant Analysis extension of Independent Components Analysis was applied to the mass spectral data. After meat ingestion, the urinary excretion of 1-methylhistidine, phenylacetylglutamine and short and medium-chained acylcarnitines was observed. 15 N labelling was detected in these metabolites thus confirming their origin from ingested meat. However, no difference was observed in urinary metabolomic profiles according to the meat cooking process used. CONCLUSION: Meat ingestion led to the excretion of several nitrogen-containing compounds, but although a metabolic signature was detected for meat ingestion, the impact of cooking process was not detectable at the level of urinary metabolic signature in our experimental conditions. This article is protected by copyright. All rights reserved. PMID: 29468821 [PubMed - as supplied by publisher]