PubMed

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation. JCI Insight. 2017 Oct 05;2(19): Authors: Bhargava P, Fitzgerald KC, Calabresi PA, Mowry EM Abstract BACKGROUND: Our goal was to identify changes in the metabolome in multiple sclerosis (MS) and how vitamin D supplementation alters metabolic profiles in MS patients and healthy controls. METHODS: We applied global untargeted metabolomics to plasma from a cross-sectional cohort of age- and sex-matched MS patients and controls and a second longitudinal cohort of MS patients and healthy controls who received 5,000 IU cholecalciferol daily for 90 days. We applied partial least squares discriminant analysis, weighted correlation network analysis (WGCNA), and pathway analysis to the metabolomics data. Generalized estimating equations models were used to assess change in WGCNA-identified module scores or metabolite pathways with vitamin D supplementation. RESULTS: Utilizing multiple analytical techniques, we identified metabolic alterations in oxidative stress (γ-glutamyl amino acid, glutathione) and xenobiotic metabolism (benzoate, caffeine) in MS patients compared with healthy controls in the first cohort. In the vitamin D supplementation cohort, we identified two sets of metabolites altered differentially between MS patients and healthy controls with vitamin D supplementation. The first included markers of oxidative stress and protein oxidation (P = 0.006), while the second contained lysolipids and fatty acids (P = 0.03). CONCLUSIONS: Using metabolomics, we identified alterations in oxidative stress and xenobiotic metabolism in MS patients and subsequently demonstrated a reduction of oxidative stress markers with vitamin D supplementation in healthy controls but not in MS patients. We demonstrate the utility of metabolomics in identifying aberrant metabolic processes and in monitoring the ability of therapeutic interventions to correct these abnormalities. TRIAL REGISTRATION: ClinicalTrials.gov NCT01667796. FUNDING: This study was supported by NIH grant K23 NS067055, grants from the Race to Erase MS, the National Multiple Sclerosis Society, the American Academy of Neurology, and North American Research Committee on Multiple Sclerosis. PMID: 28978801 [PubMed - as supplied by publisher]

Disruption of glucagon receptor signaling causes hyperaminoacidemia exposing a possible liver - alpha-cell axis. Am J Physiol Endocrinol Metab. 2017 Oct 03;:ajpendo.00198.2017 Authors: Galsgaard KD, Winther-Sørensen M, Ørskov C, Kissow H, Poulsen SS, Vilstrup H, Prehn C, Adamski J, Jepsen SL, Hartmann B, Hunt J, Charron MJ, Pedersen J, Wewer Albrechtsen NJ, Holst JJ Abstract Glucagon secreted from the pancreatic alpha-cells is essential for regulation of blood glucose levels. However, glucagon may play an equally important role in the regulation of amino acid metabolism by promoting ureagenesis. We hypothesized that disruption of glucagon receptor signaling would lead to an increased plasma concentration of amino acids, which in a feedback manner stimulates the secretion of glucagon, eventually associated with compensatory proliferation of the pancreatic alpha-cells. To address this, we performed plasma profiling of glucagon receptor knockout (Gcgr(-/-)) mice and wild-type (WT) littermates using liquid chromatography mass spectrometry (LC-MS)-based metabolomics, and tissue biopsies from the pancreas were analyzed for islet hormones and by histology. A principal component analysis of the plasma metabolome from Gcgr(-/-) and WT littermates indicated amino acids as the primary metabolic component distinguishing the two groups of mice. Apart from their hyperaminoacidemia, Gcgr(-/-) mice display hyperglucagonemia, increased pancreatic content of glucagon and somatostatin (but not insulin), and alpha-cell hyperplasia and hypertrophy compared to WT littermates. Incubating cultured α-TC1.9 cells with a mixture of amino acids (Vamin 1%) for 30 minutes and for up to 48 hours led to increased glucagon concentrations (~six-fold) in the media and cell proliferation (~two-fold), respectively. In anesthetized mice, a glucagon receptor specific antagonist (Novo Nordisk 25-2648, 100 mg/kg) reduced amino acid clearance. Our data supports the notion that glucagon secretion and hepatic amino acid metabolism are linked in a close feedback loop, which operates independently of normal variations in glucose metabolism. PMID: 28978545 [PubMed - as supplied by publisher]

Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS. Toxicol Ind Health. 2017 Jan 01;:748233717731959 Authors: Ma J, Sun F, Chen B, Tu X, Peng X, Wen C, Hu L, Wang X Abstract We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg(-1)) poisoning group, a pirfenidone (20 mg kg(-1)) treatment group, and a pirfenidone (40 mg kg(-1)) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg(-1)) treatment group was separated farther than the pirfenidone (20 mg kg(-1)) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning. PMID: 28978283 [PubMed - as supplied by publisher]

Metabolomic biomarkers of pancreatic cancer: a meta-analysis study. Oncotarget. 2017 Sep 15;8(40):68899-68915 Authors: Mehta KY, Wu HJ, Menon SS, Fallah Y, Zhong X, Rizk N, Unger K, Mapstone M, Fiandaca MS, Federoff HJ, Cheema AK Abstract Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures. Here, we attempted to externally replicate proposed metabolite biomarkers of PC reported by several other groups in an independent group of PC subjects. Our study design included a T2DM cohort that was used as a non-cancer control and a separate cohort diagnosed with colorectal cancer (CRC), as a cancer disease control to eliminate possible generic biomarkers of cancer. We used targeted mass spectrometry for quantitation of literature-curated metabolite markers and identified a biomarker panel that discriminates between normal controls (NC) and PC patients with high accuracy. Further evaluation of our model with CRC, however, showed a drop in specificity for the PC biomarker panel. Taken together, our study underscores the need for a more robust study design for cancer biomarker studies so as to maximize the translational value and clinical implementation. PMID: 28978166 [PubMed]

Effects of the Kinase Inhibitor Sorafenib on Heart, Muscle, Liver, and Plasma Metabolism In Vivo using Non-Targeted Metabolomics Analysis. Br J Pharmacol. 2017 Oct 04;: Authors: Jensen BC, Parry TL, Huang W, Beak JY, Ilaiwy A, Bain JR, Newgard CB, Muehlbauer MJ, Patterson C, Johnson GL, Willis MS Abstract BACKGROUND AND PURPOSE: The human kinome consists of roughly 500 kinases, including 150 that have been proposed as therapeutic targets. Protein kinases regulate an array of signaling pathways that control metabolism, cell cycle progression, cell death, differentiation, and survival. It is not surprising, then, that new kinase inhibitors (KIs) developed to treat cancer, including sorafenib, also exhibit cardiotoxicity. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical roles of protein kinases in cardiac metabolism. EXPERIMENTAL APPROACH: FVB/N mice (10 per group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity in sorafenib-treated mice compared to vehicle treated controls. Heart, skeletal muscle, liver, and plasma were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. KEY RESULTS: Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism (25-fold enrichment) by pathway enrichment analysis. CONCLUSIONS AND IMPLICATIONS: These studies identify alterations in taurine/hypotaurine metabolism in the hearts and skeletal muscles of mice treated with sorafenib. Interventions to rescue or prevent sorafenib-related cardiotoxicity by targeting the induced taurine/hypotaurine deficiency identified in the current study. PMID: 28977680 [PubMed - as supplied by publisher]

Metabolomic profile of arterial stiffness in aged adults. Diab Vasc Dis Res. 2017 Oct 01;:1479164117733627 Authors: Koh AS, Gao F, Liu J, Fridianto KT, Ching J, Tan RS, Wong JI, Chua SJ, Leng S, Zhong L, Keng BM, Huang FQ, Yuan JM, Koh WP, Kovalik JP Abstract BACKGROUND: Increasing arterial stiffness is an important contributor to declining cardiovascular health in ageing. Changes in whole-body fuel metabolism could be related to alterations in arterial stiffness in ageing adults. METHODS: Targeted high-performance liquid and gas chromatography mass spectrometry were used to measure 84 circulating metabolites in a group of community elderly adults ( n = 141, 58% men; mean age = 70.6 ± 11.2 years) without cardiovascular disease. In basic and adjusted models, we correlated the measured metabolites to carotid-femoral pulse wave velocity assessed by applanation tonometry. RESULTS: Age ( β = 0.10, p < 0.0001), smoking status ( β = 1.32, p = 0.02), dyslipidemia ( β = 1.22, p = 0.01), central systolic blood pressure ( β = 0.05, p < 0.0001), central mean arterial pressure ( β = 0.04, p = 0.03) and central pulse pressure ( β = 0.05, p < 0.0001) were significantly associated with pulse wave velocity. Amino acids such as histidine, methionine and valine correlated with pulse wave velocity. In multivariable models adjusted for clinical covariates, only Factor 5, comprising the medium- and long-chain dicarboxyl and hydroxyl acylcarnitines was independently associated with pulse wave velocity ( β = 0.24, p = 0.015). CONCLUSION: An upstream metabolic perturbation comprising medium- and long-chain dicarboxyl and hydroxyl acylcarnitines, likely reflecting changes in cellular fatty acid oxidation, was associated with arterial stiffness among aged adults. This advances mechanistic understanding of arterial stiffness among aged adults before clinical disease. PMID: 28976207 [PubMed - as supplied by publisher]

Urine metabolomics insight into acute kidney injury point to oxidative stress disruptions in energy generation and H2S availability. J Mol Med (Berl). 2017 Oct 04;: Authors: Martin-Lorenzo M, Gonzalez-Calero L, Ramos-Barron A, Sanchez-Niño MD, Gomez-Alamillo C, García-Segura JM, Ortiz A, Arias M, Vivanco F, Alvarez-Llamas G Abstract Acute kidney injury (AKI) is one of the main complications in acute care medicine and a risk factor for chronic kidney disease (CKD). AKI incidence has increased; however, its diagnosis has limitations and physiopathological mechanisms are underexplored. We investigated urine samples, aiming to identify major metabolite changes during human AKI evolution. Metabolic signatures found were further explored for a potential link to severity of injury. Twenty-four control subjects and 38 hospitalized patients with AKI were recruited and urine samples were collected at the time of diagnosis, during follow-up and at discharge. Nuclear magnetic resonance (NMR) was used in a first discovery phase for identifying potential metabolic differences. Target metabolites of interest were confirmed by liquid chromatography-mass spectrometry (LC-MS/MS) in an independent group. Underlying metabolic defects were further explored by kidney transcriptomics of murine toxic AKI. Urinary 2-hydroxybutyric acid, pantothenic acid, and hippuric acid were significantly downregulated and urinary N-acetylneuraminic acid, phosphoethanolamine, and serine were upregulated during AKI. Hippuric acid, phosphoethanolamine, and serine showed further downregulation/upregulation depending on the metabolite in acute tubular necrosis (ATN) AKI compared to prerenal AKI. Kidney transcriptomics disclosed decreased expression of cystathionase, cystathionine-β-synthase, and ethanolamine-phosphate cytidylyltransferase, and increased N-acetylneuraminate synthase as the potentially underlying cause of changes in urinary metabolites. A urinary metabolite panel identified AKI patients and provided insight into intrarenal events. A urine fingerprint made up of six metabolites may be related to pathophysiological changes in oxidative stress, energy generation, and H2S availability associated with AKI. KEY MESSAGES: The urinary metabolome reflects AKI evolution and severity of injury. Kidney transcriptomics revealed enzymatic expression changes. Enzymatic expression changes may be the potentially underlying cause of changes in urine metabolites. Identified metabolite changes link oxidative stress, energy generation, and H2S availability to AKI. PMID: 28975359 [PubMed - as supplied by publisher]

Dietary and health biomarkers-time for an update. Genes Nutr. 2017;12:24 Authors: Dragsted LO, Gao Q, Praticò G, Manach C, Wishart DS, Scalbert A, Feskens EJM Abstract In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health. The implementation of biomarkers in nutritional research will be important to improve measurements of dietary intake, exposure to specific dietary components, and of compliance to dietary interventions. Biomarkers could also help with improved characterization of nutritional status in study volunteers and to provide much mechanistic insight into the effects of food components and diets. Although hundreds of papers in nutrition are published annually, there is no current ontology for the area, no generally accepted classification terminology for biomarkers in nutrition and health, no systematic validation scheme for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under the Joint Programming Initiative-A Healthy Diet for a Healthy Life (JPI-HDHL)-is aimed at meeting some of these challenges, identifying new dietary biomarkers, and producing new databases and review papers on biomarkers for nutritional research. This current paper outlines the needs and serves as an introduction to this thematic issue of Genes & Nutrition on dietary and health biomarkers. PMID: 28974991 [PubMed]

Related Articles Next-Generation Breast Cancer Omics. Am J Pathol. 2017 Oct;187(10):2130-2132 Authors: Coleman WB Abstract This Editorial highlights the reviews in the Breast Cancer Theme Issue that features topics related to next-generation breast cancer omics. PMID: 28822804 [PubMed - indexed for MEDLINE]

Related Articles Lactate dehydrogenase activity drives hair follicle stem cell activation. Nat Cell Biol. 2017 Sep;19(9):1017-1026 Authors: Flores A, Schell J, Krall AS, Jelinek D, Miranda M, Grigorian M, Braas D, White AC, Zhou JL, Graham NA, Graeber T, Seth P, Evseenko D, Coller HA, Rutter J, Christofk HR, Lowry WE Abstract Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli. PMID: 28812580 [PubMed - indexed for MEDLINE]

Related Articles Gene expression and metabolite profiling of gibberellin biosynthesis during induction of somatic embryogenesis in Medicago truncatula Gaertn. PLoS One. 2017;12(7):e0182055 Authors: Igielski R, Kępczyńska E Abstract Gibberellins (GAs) are involved in the regulation of numerous developmental processes in plants including zygotic embryogenesis, but their biosynthesis and role during somatic embryogenesis (SE) is mostly unknown. In this study we show that during three week- long induction phase, when cells of leaf explants from non-embryogenic genotype (M9) and embryogenic variant (M9-10a) were forming the callus, all the bioactive gibberellins from non-13-hydroxylation (GA4, GA7) and 13-hydroxylation (GA1, GA5, GA3, GA6) pathways were present, but the contents of only a few of them differed between the tested lines. The GA53 and GA19 substrates synthesized by the 13-hydroxylation pathway accumulated specifically in the M9-10a line after the first week of induction; subsequently, among the bioactive gibberellins detected, only the content of GA3 increased and appeared to be connected with acquisition of embryogenic competence. We fully annotated 20 Medicago truncatula orthologous genes coding the enzymes which catalyze all the known reactions of gibberellin biosynthesis. Our results indicate that, within all the genes tested, expression of only three: MtCPS, MtGA3ox1 and MtGA3ox2, was specific to embryogenic explants and reflected the changes observed in GA53, GA19 and GA3 contents. Moreover, by analyzing expression of MtBBM, SE marker gene, we confirmed the inhibitory effect of manipulation in GAs metabolism, applying exogenous GA3, which not only impaired the production of somatic embryos, but also significantly decreased expression of this gene. PMID: 28750086 [PubMed - indexed for MEDLINE]

Related Articles Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: Findings from the National Diet and Nutrition Survey. PLoS One. 2017;12(7):e0182195 Authors: Potter GDM, Cade JE, Hardie LJ Abstract Ever more evidence associates short sleep with increased risk of metabolic diseases such as obesity, which may be related to a predisposition to non-homeostatic eating. Few studies have concurrently determined associations between sleep duration and objective measures of metabolic health as well as sleep duration and diet, however. We therefore analyzed associations between sleep duration, diet and metabolic health markers in UK adults, assessing associations between sleep duration and 1) adiposity, 2) selected metabolic health markers and 3) diet, using National Diet and Nutrition Survey data. Adults (n = 1,615, age 19-65 years, 57.1% female) completed questions about sleep duration and 3 to 4 days of food diaries. Blood pressure and waist circumference were recorded. Fasting blood lipids, glucose, glycated haemoglobin (HbA1c), thyroid hormones, and high-sensitivity C-reactive protein (CRP) were measured in a subset of participants. We used regression analyses to explore associations between sleep duration and outcomes. After adjustment for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with body mass index (-0.46 kg/m2 per hour, 95% CI -0.69 to -0.24 kg/m2, p < 0.001) and waist circumference (-0.9 cm per hour, 95% CI -1.5 to -0.3cm, p = 0.004), and positively associated with high-density lipoprotein cholesterol (0.03 mmol/L per hour, 95% CI 0.00 to 0.05, p = 0.03). Sleep duration tended to be positively associated with free thyroxine levels and negatively associated with HbA1c and CRP (p = 0.09 to 0.10). Contrary to our hypothesis, sleep duration was not associated with any dietary measures (p ≥ 0.14). Together, our findings show that short-sleeping UK adults are more likely to have obesity, a disease with many comorbidities. PMID: 28750055 [PubMed - indexed for MEDLINE]

Related Articles The Evolving Role of Companion Diagnostics for Breast Cancer in an Era of Next-Generation Omics. Am J Pathol. 2017 Oct;187(10):2185-2198 Authors: Rosenbaum JN, Weisman P Abstract A companion diagnostic is a test for a specific biomarker-approved by the United States Food and Drug Administration-qualifying a patient to receive a specific, associated therapy. As interest has grown in precision medicine over the past decade, the principle of companion diagnostics has gained increasing purchase among laboratory professionals, clinicians, regulators, and even patients. The evolution of the biomarkers used to stratify and treat breast cancer illustrates the history of companion diagnostics and provides a lens through which to examine potential challenges. As new targeted therapies and corresponding biomarkers accumulate, algorithms for diagnosis and treatment necessarily become lengthier and more complex. To accommodate future needs of breast cancer patients, the companion diagnostic model will continue to adapt and evolve. PMID: 28733195 [PubMed - indexed for MEDLINE]

Related Articles An engineered photoswitchable mammalian pyruvate kinase. FEBS J. 2017 Sep;284(18):2955-2980 Authors: Gehrig S, Macpherson JA, Driscoll PC, Symon A, Martin SR, MacRae JI, Kleinjung J, Fraternali F, Anastasiou D Abstract Changes in allosteric regulation of glycolytic enzymes have been linked to metabolic reprogramming involved in cancer. Remarkably, allosteric mechanisms control enzyme function at significantly shorter time-scales compared to the long-term effects of metabolic reprogramming on cell proliferation. It remains unclear if and how the speed and reversibility afforded by rapid allosteric control of metabolic enzymes is important for cell proliferation. Tools that allow specific, dynamic modulation of enzymatic activities in mammalian cells would help address this question. Towards this goal, we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24]), an engineered pyruvate kinase M2 (PKM2) variant that harbours an insertion of the light-sensing LOV2 domain from Avena Sativa within a region implicated in allosteric regulation by fructose 1,6-bisphosphate (FBP). The LOV2 photoreaction is preserved in the PiL[D24] chimera and causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure. Importantly, this change in activity is reversible upon light withdrawal. Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose. PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner and paves the way for studying the importance of rapid allosteric phenomena in the regulation of metabolism and enzyme control. PMID: 28715126 [PubMed - indexed for MEDLINE]

Related Articles Glycolysis and pyrimidine biosynthesis are required for replication of adherent-invasive Escherichia coli in macrophages. Microbiology. 2016 Jun;162(6):954-65 Authors: Thompson AP, O'Neill I, Smith EJ, Catchpole J, Fagan A, Burgess KE, Carmody RJ, Clarke DJ Abstract Adherent-invasive Escherichia coli (AIEC) have been implicated in the aetiology of Crohn's disease (CD), a chronic inflammatory bowel condition. It has been proposed that AIEC-infected macrophages produce high levels of pro-inflammatory cytokines thus contributing to the inflammation observed in CD. AIEC can replicate in macrophages and we wanted to determine if bacterial replication was linked to the high level of cytokine production associated with AIEC-infected macrophages. Therefore, we undertook a genetic analysis of the metabolic requirements for AIEC replication in the macrophage and we show that AIEC replication in this niche is dependent on bacterial glycolysis. In addition, our analyses indicate that AIEC have access to a wide range of nutrients in the macrophage, although the levels of purines and pyrimidines do appear to be limiting. Finally, we show that the macrophage response to AIEC infection is indistinguishable from the response to the non-replicating glycolysis mutant (ΔpfkAB) and a non-pathogenic strain of E. coli, MG1655. Therefore, AIEC does not appear to subvert the normal macrophage response to E. coli during infection. PMID: 27058922 [PubMed - indexed for MEDLINE]

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Ms2lda.org: web-based topic modelling for substructure discovery in mass spectrometry. Bioinformatics. 2017 Sep 14;: Authors: Wandy J, Zhu Y, van der Hooft JJJ, Daly R, Barrett MP, Rogers S Abstract Motivation: We recently published MS2LDA, a method for the decomposition of sets of molecular fragment data derived from large metabolomics experiments. To make the method more widely available to the community, here we present ms2lda.org, a web application that allows users to upload their data, run MS2LDA analyses and explore the results through interactive visualisations. Results: Ms2lda.org takes tandem mass spectrometry data in many standard formats and allows the user to infer the sets of fragment and neutral loss features that co-occur together (Mass2Motifs). As an alternative workflow, the user can also decompose a dataset onto predefined Mass2Motifs. This is accomplished through the web interface or programmatically from our web service. Availability and Implementation: The website can be found at http://ms2lda.org , while the source code is available at https://github.com/sdrogers/ms2ldaviz under the MIT license. Contact: simon.rogers@glasgow.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online. PMID: 28968802 [PubMed - as supplied by publisher]

A sensitive and accurate method to simultaneously measure uric acid and creatinine in human saliva by using LC-MS/MS. Bioanalysis. 2017 Oct 02;: Authors: Liu XY, Luo Y, Zhou CY, Peng A, Liu JY Abstract AIM: To establish a method to simultaneously measure uric acid (UA) and creatinine (Cr) in human saliva. MATERIALS & METHODS: By using HPLC-MS/MS, we developed and validated a fast, sensitive and accurate method to simultaneously determine UA and Cr in human saliva. The determination range for Cr and UA is of 10-5000 ng/ml with the R(2) for both calibration curves over 0.999. The accuracy, precision and recovery of Cr and UA were all acceptable. By using the established method, the Cr and UA levels in saliva from 28 healthy volunteers were measured as 2.9 ± 0.8 µM and 46.8 ± 18.2 µM, respectively. CONCLUSION: This method can simultaneously determine Cr and UA in saliva for clinical and translational study. PMID: 28967800 [PubMed - as supplied by publisher]

The hypoglycemic and antioxidant effects of polysaccharides from the petioles and pedicels of Euryale ferox Salisb. on alloxan-induced hyperglycemic mice. Food Funct. 2017 Oct 02;: Authors: Wu CY, Wang H, He XX, Wu DW, Yue W, Wu QN Abstract The present study investigated the potential hypoglycemic and antioxidant effects of polysaccharides extracted from the petioles and pedicels of Euryale ferox Salisb. (EFPP) on alloxan-induced hyperglycemic mice. The EFPP had a total carbohydrate of 65.72 ± 2.81%, uronic acid of 4.56 ± 0.62% and protein of 0.58 ± 0.12%, with an average molecular weight from 1.02 kDa to 11.45 kDa and monosaccharide composition of Man, GlcA, Rha, Glc, Gal and Ara at a molar ratio of 0.12 : 0.01 : 9.57 : 0.41 : 1.00 : 0.24. Administration with EFPP, especially high dose EFPP, was beneficial to reverse body weight loss, reduce blood glucose levels, enhance serum insulin levels, improve oral glucose tolerance, increase hepatic glycogen content and GCK activity, and modulate the mRNA expression of GCK in the liver. Meanwhile, EFPP had protective effects against alloxan-induced oxidative injury in mice, via increasing the activities of SOD, CAT and GSH-Px and decreasing the MDA contents in the liver and kidney of the mice. EFPP ameliorated the damage in pancreas, kidney and liver tissues, which was confirmed by histopathological observation. The results suggested that EFPP possess hypoglycemic and antioxidant activities, and could be a potential source of natural hypoglycemic and antioxidant agents for functional foods or complementary medicines. PMID: 28967662 [PubMed - as supplied by publisher]

Related Articles A plasma metabonomic analysis on potential biomarker in pyrexia induced by three methods using ultra high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Sep 15;1063:214-225 Authors: Liu T, Li S, Tian X, Li Z, Cui Y, Han F, Zhao Y, Yu Z Abstract Pyrexia usually is a systemic pathological process that can lead to metabolic disorders. Metabonomics as a powerful tool not only can reveal the pathological mechanisms, but also can give insight into the progression of pyrexia from another angle. Thus, an ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) metabonomic approach was employed for the first time to investigate the plasma biochemical characteristics of pyrexia induced by three methods and to reveal subtle metabolic changes under the condition of pyrexia so as to explore its mechanism. The acquired metabolic data of the models were subjected to principal component analysis (PCA) for allowing the clear separation of the pyrexia rats from the control rats. Variable importance for project values (VIP) and Student's t-test were used to screen the significant metabolic changes caused by pyrexia. Fifty-two endogenous metabolites were identified and putatively identified as potential biomarkers primarily associated with phospholipid metabolism, sphingolipid metabolism, fatty acid oxidation metabolism, fatty acid amides metabolism and amino acid metabolism, and related to bile acid biosynthesis and glycerolipid catabolism. LysoPC (14:0), LysoPC (18:3), LysoPC (20:4), LysoPC (16:0), phytosphingosine, Cer (d18:0/12:0), N-[(4E,8E)-1,3-dihydroxyoctadeca-4,8-dien-2-yl]hexadecanamide, oleamide, fatty acid amide C22:1, tryptophan, acetylcarnitine, palmitoylcarnitine and stearoylcarnitine were considered as common potential biomarkers of pyrexia rats induced by three methods: Our results revealed that the UHPLC-FT-ICR-MS-based metabolomic method is helpful for finding new potential metabolic markers for pyrexia detection and offers a good perspective in pyrexia research. PMID: 28886580 [PubMed - indexed for MEDLINE]