PubMed

Related Articles Metabolomics in the Clinic: A Review of the Shared and Unique Features of Untargeted Metabolomics for Clinical Research and Clinical Testing. J Mass Spectrom. 2018 Sep 22;: Authors: Kennedy AD, Wittmann BM, Evans AM, Miller LAD, Toal DR, Lonergan S, Elsea SH, Pappan KL Abstract Metabolomics is the untargeted measurement of the metabolome, which is comprised of the complement of small molecules detected in a biological sample. As such, metabolomic analysis produces a global biochemical phenotype. It is a technology that has been utilized in the research setting for over a decade. The metabolome is directly linked to and is influenced by genetics, epigenetics, environmental factors and the microbiome - all of which affect health. Metabolomics can be applied to human clinical diagnostics and to other fields such as veterinary medicine, nutrition, exercise, physiology, agriculture/plant biochemistry, and toxicology. Applications of metabolomics in clinical testing are emerging, but several aspects of its use as a clinical test differ from applications focused on research or biomarker discovery and need to be considered for metabolomics clinical test data to have optimum impact, be meaningful, and be used responsibly. In this review, we deconstruct aspects and challenges of metabolomics for clinical testing by illustrating the significance of test design, accurate and precise data acquisition, quality control, data processing, n-of-1 comparison to a reference population, and biochemical pathway analysis. We describe how metabolomics technology is integral to defining individual biochemical phenotypes, elaborates on human health and disease, and fits within the precision medicine landscape. Finally, we conclude by outlining some future steps needed to bring metabolomics into the clinical space and to be recognized by the broader medical and regulatory fields. PMID: 30242936 [PubMed - as supplied by publisher]

Related Articles Effects of Centella asiatica extract on antioxidant status and liver metabolome of rotenone-treated rats using GC-MS. Biomed Chromatogr. 2018 Sep 22;:e4395 Authors: Intararuchikul T, Teerapattarakan N, Rodsiri R, Tantisira M, Wohlgemuth G, Fiehn O, Tansawat R Abstract Centella asiatica has been used as culinary vegetable or medicinal herb. In this study, hepatoprotective effect of the standardized extract of Centella asiatica (ECa233) in rotenone-treated rats was examined using a GC-MS based metabolomic approach. ECa233 contains >80% triterpenoids with a ratio of madecassoside to asiaticoside of 1.5(±0.5):1. Rats were randomly divided into three groups (with six rats/group): sham negative control, rotenone positive control, and the ECa233 test group. Rats in the ECa233 group received 10 mg/kg ECa233 orally for 20 days, followed by 2.5 mg/kg intraperitoneal rotenone injection to induce toxicity before being sacrificed. Metabolomic analysis showed that supplementation of ECa233 protected rat liver against rotenone toxicity. Pipecolinic acid was one of the most important metabolites; its level was decreased in the rotenone group as compared to control. Supplementation with ECa233 before administration of rotenone raised pipecolinic acid to levels intermediate between controls and rotenone alone. Metabolomics approach also helped discover a possible new genuine epimetabolite in the present work. Antioxidant tests revealed that ECa233 inhibited lipid peroxidation and increased catalase activities in liver tissue. PMID: 30242859 [PubMed - as supplied by publisher]

Related Articles Responses to K deficiency and waterlogging interact via respiratory and nitrogen metabolism. Plant Cell Environ. 2018 Sep 22;: Authors: Cui J, Abadie C, Carroll A, Lamade E, Tcherkez G Abstract K deficiency and waterlogging are common stresses that can occur simultaneously and impact on crop development and yield. They are both known to affect catabolism, with rather opposite effects: inhibition of glycolysis and higher glycolytic fermentative flux, respectively. But surprisingly, the effect of their combination on plant metabolism has never been examined precisely. Here, we applied a combined treatment (K availability, waterlogging) to sunflower (Helianthus annuus L.) plants under controlled greenhouse conditions, and performed elemental quantitation, metabolomics and isotope analyses at different sampling times. While separate K deficiency and waterlogging caused well-known effects like polyamines production and sugar accumulation, respectively, waterlogging altered K-induced respiration enhancement (via the C5 -branched acid pathway) and polyamine production, and K deficiency tended to suppress waterlogging-induced accumulation of Krebs cycle intermediates in leaves. Furthermore, the natural 15 N/14 N isotope composition (δ15 N) in leaf compounds shows that there was a change in nitrate circulation, with less nitrate influx to leaves under low K availablity combined with waterlogging, and more isotopic dilution of lamina nitrates under high K. Our results show that K deficiency and waterlogging effects are not simply additive, reshape respiration as well as nitrogen metabolism and partitioning, and are associated with metabolomic and isotopic biomarkers of potential interest for crop monitoring. PMID: 30242853 [PubMed - as supplied by publisher]

Related Articles Plasma lipid profiling of tissue-specific insulin resistance in human obesity. Int J Obes (Lond). 2018 Sep 21;: Authors: van der Kolk BW, Vogelzangs N, Jocken JWE, Valsesia A, Hankemeier T, Astrup A, Saris WHM, Arts ICW, van Greevenbroek MMJ, Blaak EE, DiOGenes consortium Abstract BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance (IR) may develop in multiple organs, representing different aetiologies towards cardiometabolic diseases. This study aimed to identify distinct plasma lipid profiles in overweight/obese individuals who show muscle-IR and/or liver-IR. SUBJECTS/METHODS: Baseline data of the European multicenter DiOGenes project were used (n = 640; 401 women, nondiabetic BMI: 27-45 kg/m2). Muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI) were derived from a 5-point oral glucose tolerance test. The 140 plasma lipids were quantified by liquid chromatography-mass spectrometry. Linear mixed models were used to evaluate associations between MISI, HIRI and plasma lipids. RESULTS: MISI was comparable between sexes while HIRI and triacylglycerol (TAG) levels were lower in women than in men. MISI was associated with higher lysophosphatidylcholine (LPC) levels (standardized (std)β = 0.126; FDR-p = 0.032). Sex interactions were observed for associations between HIRI, TAG and diacylglycerol (DAG) lipid classes. In women, but not in men, HIRI was associated with higher levels of TAG (44 out of 55 species) and both DAG species (stdβ: 0.139-0.313; FDR-p < 0.05), a lower odd-chain/even-chain TAG ratio (stdβ = -0.182; FDR-p = 0.005) and a lower very-long-chain/long-chain TAG ratio (stdβ = -0.156; FDR-p = 0.037). CONCLUSIONS: In overweight/obese individuals, muscle insulin sensitivity is associated with higher plasma LPC concentrations. Women have less hepatic IR and lower TAG than men. Nevertheless, hepatic IR is associated with higher plasma TAG and DAG concentrations and a lower abundance of odd-chain and very-long-chain TAG in women, but not in men. This suggests a more pronounced worsening of plasma lipid profile in women with the progression of hepatic IR. PMID: 30242234 [PubMed - as supplied by publisher]

Related Articles High-throughput serum N-glycomics: method comparison and application to study rheumatoid arthritis and pregnancy-associated changes. Mol Cell Proteomics. 2018 Sep 21;: Authors: Reiding KR, Bondt A, Hennig R, Gardner RA, O'Flaherty R, Trbojević-Akmačić I, Shubhakar A, Hazes J, Reichl U, Fernandes DL, Pucic-Bakovic M, Rapp E, Spencer DIR, Dolhain R, Rudd P, Lauc G, Wuhrer M Abstract N-Glycosylation is a fundamentally important protein modification with a major impact on glycoprotein characteristics such as serum half-life and receptor interaction. More than half of the proteins in human serum are glycosylated, and the relative abundances of protein glycoforms often reflect alterations in health and disease. Several analytical methods are currently capable of analyzing the total serum N-glycosylation in a high-throughput manner.Here we evaluate and compare the performance of three high-throughput released N-glycome analysis methods. Included were hydrophilic-interaction ultra-high-performance liquid chromatography with fluorescence detection (HILIC-UHPLC-FLD) with 2-aminobenzamide labeling of the glycans, multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) with 8-aminopyrene-1-3,6-trisulfonic acid labeling, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with linkage-specific sialic acid esterification. All methods assessed the same panel of serum samples, which were obtained at multiple time points during the pregnancies and postpartum periods of healthy women and patients with rheumatoid arthritis (RA). We compared the analytical methods on their technical performance as well as on their ability to describe serum protein N-glycosylation changes throughout pregnancy, with RA, and with RA disease activity.Overall, the methods proved to be similar in their detection and relative quantification of serum protein N-glycosylation. However, the non-MS methods showed superior repeatability over MALDI-TOF-MS, and allowed the best structural separation of low-complexity N-glycans. MALDI-TOF-MS achieved the highest throughput and provided compositional information on higher-complexity N-glycans. Consequentially, MALDI-TOF-MS could establish the linkage-specific sialylation differences within pregnancy and RA, whereas HILIC-UHPLC-FLD and xCGE-LIF demonstrated differences in α1,3- and α1,6-branch galactosylation. While the combination of methods proved to be the most beneficial for the analysis of total serum protein N-glycosylation, informed method choices can be made for the glycosylation analysis of single proteins or samples of varying complexity. PMID: 30242110 [PubMed - as supplied by publisher]

Related Articles Biomarkers of dementia in obstructive sleep apnea. Sleep Med Rev. 2018 Aug 13;: Authors: Baril AA, Carrier J, Lafrenière A, Warby S, Poirier J, Osorio RS, Ayas N, Dubé MP, Petit D, Gosselin N, Canadian Sleep and Circadian Network Abstract Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decision-making. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer's disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk. PMID: 30241998 [PubMed - as supplied by publisher]

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 2018/09/22PubMed 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.

17 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 2018/09/21PubMed 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.

Particulate metal exposures induce plasma metabolome changes in a commuter panel study. PLoS One. 2018;13(9):e0203468 Authors: Ladva CN, Golan R, Liang D, Greenwald R, Walker DI, Uppal K, Raysoni AU, Tran V, Yu T, Flanders WD, Miller GW, Jones DP, Sarnat JA Abstract INTRODUCTION: Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. METHODS: A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. RESULTS: HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. CONCLUSIONS: Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation. PMID: 30231074 [PubMed - in process]

Structural and Functional Analysis of the Gut Microbiome for Toxicologists. Curr Protoc Toxicol. 2018 Sep 19;:e54 Authors: Nichols RG, Cai J, Murray IA, Koo I, Smith PB, Perdew GH, Patterson AD Abstract Characterizing the reciprocal interactions between toxicants, the gut microbiota, and the host, holds great promise for improving our mechanistic understanding of toxic endpoints. Advances in culture-independent sequencing analysis (e.g., 16S rRNA gene amplicon sequencing) combined with quantitative metabolite profiling (i.e., metabolomics) have provided new ways of studying the gut microbiome and have begun to illuminate how toxicants influence the structure and function of the gut microbiome. Developing a standardized protocol is important for establishing robust, reproducible, and importantly, comparative data. This protocol can be used as a foundation for examining the gut microbiome via sequencing-based analysis and metabolomics. Two main units follow: (1) analysis of the gut microbiome via sequencing-based approaches; and (2) functional analysis of the gut microbiome via metabolomics. © 2018 by John Wiley & Sons, Inc. PMID: 30230220 [PubMed - as supplied by publisher]

Fine-tuning of SIRT1 expression is essential to protect the liver from cholestatic liver disease. Hepatology. 2018 Sep 19;: Authors: Blokker BA, Maijo M, Echeandia M, Galduroz M, Patterson AM, Ten A, Philo M, Schungel R, Gutierrez-de Juan V, Halilbasic E, Fuchs C, Le Gall G, Milkiewicz M, Milkiewicz P, Banales JM, Rushbrook SM, Mato JM, Trauner M, Müller M, Martínez-Chantar ML, Varela-Rey M, Beraza N Abstract Cholestasis comprises aetiologically heterogeneous conditions characterized by accumulation of bile acids in the liver that actively contribute to liver damage. Sirtuin 1 (SIRT1) regulates liver regeneration and bile acid metabolism via modulating the farnesoid X receptor (FXR); we here investigate its role in cholestatic liver disease. We determined SIRT1 expression in livers from patients with cholestatic disease, in two experimental models of cholestasis, as well as in human and murine liver cells in response to bile acid loading. SIRT1 overexpressing (SIRToe ) and hepatocyte-specific SIRT1-KO mice (SIRThep-/- ) were subjected to BDL and were fed with 0.1%DDC diet to determine the biological relevance of SIRT1 during cholestasis. The effect of NorUDCA was tested in BDL/SIRToe mice. We found that SIRT1 was highly expressed in livers from cholestatic patients, mice after BDL and Mdr2-/- animals. The detrimental effects of SIRT1 during cholestasis were validated in vivo and in vitro. SIRToe mice showed exacerbated parenchymal injury whereas SIRThep-/- mice evidenced a moderate improvement after BDL and 0.1%DDC feeding. Likewise, hepatocytes isolated from SIRToe mice showed increased apoptosis in response to bile acids, while a significant reduction was observed in SIRThep-/- hepatocytes. Importantly, the decrease, but not complete inhibition of SIRT1 exerted by NorUDCA treatment correlated with pronounced improvement in liver parenchyma in BDL/SIRToe mice. Interestingly, both SIRT1 overexpression and hepatocyte-specific SIRT1 depletion correlated with inhibition of the farnesoid X receptor (FXR), whereas modulation of SIRT1 by NorUDCA associated with restored FXR-signalling. CONCLUSION: SIRT1 expression is increased during human and murine cholestasis. Fine-tuning expression of SIRT1 is essential to protect the liver from cholestatic-liver damage. This article is protected by copyright. All rights reserved. PMID: 30229970 [PubMed - as supplied by publisher]

1H NMR metabolomics identifies underlying inflammatory pathology in osteoarthritis and rheumatoid arthritis synovial joints. J Proteome Res. 2018 Sep 19;: Authors: Anderson JR, Chokesuwattanaskul S, Phelan MM, Welting TJ, Lian LY, Peffers MJ, Wright HL Abstract Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying aetiologies are markedly different. We used 1H Nuclear Magnetic Resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100µL SF was analysed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analysed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst®. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (False Discovery Rate (FDR)<0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by 1H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis. PMID: 30229649 [PubMed - as supplied by publisher]

Related Articles A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation. Int J Legal Med. 2018 Sep 18;: Authors: Rousseau G, Chao de la Barca JM, Rougé-Maillart C, Teresiński G, Jousset N, Dieu X, Chabrun F, Prunier-Mirabeau D, Simard G, Reynier P, Palmiere C Abstract INTRODUCTION: Hypothermia is a potentially lethal condition whose postmortem diagnosis is often complex to perform due to the absence of pathognomonic lesions and biomarkers. Our first study of human serum and urinary metabolome in hypothermia fatalities sought novel biomarkers with better diagnostic performances than those already existing. MATERIAL AND METHOD: Thirty-two cases of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or postmortem elements suggesting hypothermia were selected. A targeted metabolomic study allowing the detection and quantitation of 188 metabolites was performed on collected serum and urine using direct flow injection (FIA) and liquid chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS). Amino acid quantification was also carried on using an in-house LC-MS/MS method in order to replicate the results obtained with the metabolomic study. RESULTS: A discriminant metabolic signature allowing a clear separation between hypothermia and control groups was obtained in the serum. This signature was characterized by increased arginase activity and fatty acid unsaturation along with decreased levels of tryptophan in hypothermia fatalities compared to controls. By contrast, no discriminant metabolic signature separating hypothermia from control fatalities was found in urines. DISCUSSION: The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified. PMID: 30229331 [PubMed - as supplied by publisher]

Related Articles TumGrowth: An open-access web tool for the statistical analysis of tumor growth curves. Oncoimmunology. 2018;7(9):e1462431 Authors: Enot DP, Vacchelli E, Jacquelot N, Zitvogel L, Kroemer G Abstract The analysis of tumor growth curves is standard practice in experimental oncology including tumor immunology. In experimental oncology, cancer cells are inoculated into rodents (mostly mice) and their growth is monitored by measuring tumor diameter, surface or volume over time as a function of distinct treatments. Then, different groups of tumors/treatments are compared among each other for their evolution and possible responses to treatment. The R package TumGrowth has been created as a software tool allowing to carry out a series of statistical comparisons across or between groups of tumor growth curves obtained in a standard laboratory, for experimenters with limited knowledge in statistics. TumGrowth is freely available online at https://kroemerlab.shinyapps.io/TumGrowth/ and can be downloaded into any computer. It offers an exhaustive panoply of tools to visualize and analyze complex data sets including longitudinal, cross-sectional and time-to-endpoint measurements. PMID: 30228932 [PubMed]

Related Articles Development of a novel UHPLC-MS/MS-based platform to quantify amines, amino acids and methylarginines for applications in human disease phenotyping. Sci Rep. 2018 Sep 18;8(1):13987 Authors: Ahmetaj-Shala B, Olanipekun M, Tesfai A, MacCallum N, Kirkby NS, Quinlan GJ, Shih CC, Kawai R, Mumby S, Paul-Clark M, Want EJ, Mitchell JA Abstract Amine quantification is an important strategy in patient stratification and personalised medicine. This is because amines, including amino acids and methylarginines impact on many homeostatic processes. One important pathway regulated by amine levels is nitric oxide synthase (NOS). NOS is regulated by levels of (i) the substrate, arginine, (ii) amino acids which cycle with arginine and (iii) methylarginine inhibitors of NOS. However, biomarker research in this area is hindered by the lack of a unified analytical platform. Thus, the development of a common metabolomics platform, where a wide range of amino acids and methylarginines can be measured constitutes an important unmet need. Here we report a novel high-throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) platform where ≈40 amine analytes, including arginine and methylarginines can be detected and quantified on a molar basis, in a single sample of human plasma. To validate the platform and to generate biomarkers, human plasma from a well-defined cohort of patients before and after coronary artery bypass surgery, who developed systemic inflammatory response syndrome (SIRS), were analysed. Bypass surgery with SIRS significantly altered 26 amine analytes, including arginine and ADMA. Consequently, pathway analysis revealed significant changes in a range of pathways including those associated with NOS. PMID: 30228360 [PubMed - in process]

Related Articles Pan-cancer transcriptional signatures predictive of oncogenic mutations reveal that Fbw7 regulates cancer cell oxidative metabolism. Proc Natl Acad Sci U S A. 2018 05 22;115(21):5462-5467 Authors: Davis RJ, Gönen M, Margineantu DH, Handeli S, Swanger J, Hoellerbauer P, Paddison PJ, Gu H, Raftery D, Grim JE, Hockenbery DM, Margolin AA, Clurman BE Abstract The Fbw7 (F-box/WD repeat-containing protein 7) ubiquitin ligase targets multiple oncoproteins for degradation and is commonly mutated in cancers. Like other pleiotropic tumor suppressors, Fbw7's complex biology has impeded our understanding of how Fbw7 mutations promote tumorigenesis and hindered the development of targeted therapies. To address these needs, we employed a transfer learning approach to derive gene-expression signatures from The Cancer Gene Atlas datasets that predict Fbw7 mutational status across tumor types and identified the pathways enriched within these signatures. Genes involved in mitochondrial function were highly enriched in pan-cancer signatures that predict Fbw7 mutations. Studies in isogenic colorectal cancer cell lines that differed in Fbw7 mutational status confirmed that Fbw7 mutations increase mitochondrial gene expression. Surprisingly, Fbw7 mutations shifted cellular metabolism toward oxidative phosphorylation and caused context-specific metabolic vulnerabilities. Our approach revealed unexpected metabolic reprogramming and possible therapeutic targets in Fbw7-mutant cancers and provides a framework to study other complex, oncogenic mutations. PMID: 29735700 [PubMed - indexed for MEDLINE]

Related Articles Urinary Metabolomic Profiling in Chronic Hepatitis B Viral Infection Using Gas Chromatography/Mass Spectrometry Asian Pac J Cancer Prev. 2018 Mar 27;19(3):741-748 Authors: Dittharot K, Jittorntam P, Wilairat P, Sobhonslidsuk A Abstract Background: Chronic hepatitis B (CHB) can lead to cirrhosis and hepatocellular carcinoma. The metabolomic profiling has been shown to be associated with pathogenic mechanisms in many medical conditions including CHB. The purpose of this study was to investigate the urine metabolomic profiles in CHB patients by gas chromatography/mass spectrometry (GC/MS). Methods: Urine samples were collected from CHB patients (n = 20) and normal control subjects (n = 20). Metabolite profiles were assessed using GC/MS in conjunction with multivariate statistical analysis, in order to identify biomarker metabolites. Pathway analysis was performed by MetaboAnalyst 3.0 and KEGG database.Results: Twelve out of 377 metabolites were shown to be significantly different between the CHB and normal control groups (p < 0.05). These include palmitic acid, stearic acid, oleic acid, benzoic acid, butanoic acid, cholesterol, glycine, 3-heptanone, 4-heptanone, hexanal, 1-tetradecanol and naphthalene. Multivariate statistical analysis constructed using these expressed metabolites showed CHB patients can be discriminated from healthy controls with high sensitivity (95%) and specificity (85%). All the metabolic perturbations in this disease are associated with pathways of fatty acid, amino acid, bile acid and gut microbial metabolism. Conclusion: CHB patients have a specific urinary metabolomic profile. The abnormalities of fatty acid, amino acid, bile acid, and gut microbial metabolism lead to the development of disease progression. GC/MS-based assay is a promising tool for the metabolomic study in CHB. PMID: 29582629 [PubMed - indexed for MEDLINE]

Related Articles Glutathione S-transferase genes and the risk of type 2 diabetes mellitus: Role of sexual dimorphism, gene-gene and gene-smoking interactions in disease susceptibility. J Diabetes. 2018 May;10(5):398-407 Authors: Azarova I, Bushueva O, Konoplya A, Polonikov A Abstract BACKGROUND: Compromised defense against reactive oxygen species (ROS) is considered important in the pathogenesis of type 2 diabetes mellitus (T2DM); therefore, genes encoding antioxidant defense enzymes may contribute to disease susceptibility. This study investigated whether polymorphisms in genes encoding glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) jointly contribute to the risk of T2DM. METHODS: In all, 1120 unrelated Russian subjects (600 T2DM patients, 520 age- and sex-matched healthy subjects), were recruited to the study. Genotyping was performed by multiplex polymerase chain reaction (PCR; del/del polymorphisms of GSTM1 and GSTT1) and TaqMan-based PCR (polymorphisms I105V and A114V of GSTP1). Plasma ROS and glutathione levels in study subjects were analyzed by fluorometric and colorimetric assays, respectively. RESULTS: Genotype del/del GSTT1 was significantly associated with the risk of T2DM (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.17-2.21, P = 0.003). Gender-stratified analysis showed that the deletion genotypes of GSTM1 (OR 1.99, 95% CI 1.30-3.05; P = 0.0002, Q = 0.016) and GSTT1 (OR 2.23, 95% CI 1.22-4.09; P = 0.008, Q = 0.0216), as well as genotype 114A/V of GSTP1 (OR 2.85, 95% CI 1.44-5.62; P = 0.005, Q = 0.02) were associated with an increased risk of T2DM exclusively in males. Three genotype combinations (i.e. GSTM1+ × GSTT1+, GSTM1+ × GSTP1 114A/A and GSTT1+ × GSTP1 114A/A) showed significant associations with a decreased risk of T2DM in males. CONCLUSIONS: This study demonstrates, for the first time, that genes encoding glutathione S-transferases jointly contribute to the risk of T2DM, and that their effects on disease susceptibility are gender specific. PMID: 29111615 [PubMed - indexed for MEDLINE]

17 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 2018/09/19PubMed 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.

17 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 2018/09/19PubMed 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.