PubMed

Capillary Electrophoresis in Food and Foodomics. Methods Mol Biol. 2016;1483:471-507 Authors: Ibáñez C, Acunha T, Valdés A, García-Cañas V, Cifuentes A, Simó C Abstract Quality and safety assessment as well as the evaluation of other nutritional and functional properties of foods imply the use of robust, efficient, sensitive, and cost-effective analytical methodologies. Among analytical technologies used in the fields of food analysis and foodomics, capillary electrophoresis (CE) has generated great interest for the analyses of a large number of compounds due to its high separation efficiency, extremely small sample and reagent requirements, and rapid analysis. The introductory section of this chapter provides an overview of the recent applications of capillary electrophoresis (CE) in food analysis and foodomics. Relevant reviews and research articles on these topics are tabulated including papers published in the period 2011-2014. In addition, to illustrate the great capabilities of CE in foodomics the chapter describes the main experimental points to be taken into consideration for a metabolomic study of the antiproliferative effect of carnosic acid (a natural diterpene found in rosemary) against HT-29 human colon cancer cells. PMID: 27645749 [PubMed - as supplied by publisher]

Capillary Electrophoresis in Metabolomics. Methods Mol Biol. 2016;1483:437-470 Authors: Maier TV, Schmitt-Kopplin P Abstract Metabolomics is an analytical toolbox to describe (all) low-molecular-weight compounds in a biological system, as cells, tissues, urine, and feces, as well as in serum and plasma. To analyze such complex biological samples, high requirements on the analytical technique are needed due to the high variation in compound physico-chemistry (cholesterol derivatives, amino acids, fatty acids as SCFA, MCFA, or LCFA, or pathway-related metabolites belonging to each individual organism) and concentration dynamic range. All main separation techniques (LC-MS, GC-MS) are applied in routine to metabolomics hyphenated or not to mass spectrometry, and capillary electrophoresis is a powerful high-resolving technique but still underused in this field of complex samples. Metabolomics can be performed in the non-targeted way to gain an overview on metabolite profiles in biological samples. Targeted metabolomics is applied to analyze quantitatively pre-selected metabolites. This chapter reviews the use of capillary electrophoresis in the field of metabolomics and exemplifies solutions in metabolite profiling and analysis in urine and plasma. PMID: 27645748 [PubMed - as supplied by publisher]

Aberrant ketolysis fuels hepatocellular cancer progression. Cell Res. 2016 Sep 20; Authors: Galluzzi L, Kroemer G Abstract At odds with their normal counterparts, hepatocellular carcinoma cells efficiently utilize ketone bodies to proliferate despite serum deprivation. These findings, which have been recently published in Cell Research, identify a novel metabolic circuitry through which tumors successfully cope with adverse microenvironmental conditions. PMID: 27644988 [PubMed - as supplied by publisher]

Towards quantitative mass spectrometry-based metabolomics in microbial and mammalian systems. Philos Trans A Math Phys Eng Sci. 2016 Oct 28;374(2079) Authors: Kapoore RV, Vaidyanathan S Abstract Metabolome analyses are a suite of analytical approaches that enable us to capture changes in the metabolome (small molecular weight components, typically less than 1500 Da) in biological systems. Mass spectrometry (MS) has been widely used for this purpose. The key challenge here is to be able to capture changes in a reproducible and reliant manner that is representative of the events that take place in vivo Typically, the analysis is carried out in vitro, by isolating the system and extracting the metabolome. MS-based approaches enable us to capture metabolomic changes with high sensitivity and resolution. When developing the technique for different biological systems, there are similarities in challenges and differences that are specific to the system under investigation. Here, we review some of the challenges in capturing quantitative changes in the metabolome with MS based approaches, primarily in microbial and mammalian systems.This article is part of the themed issue 'Quantitative mass spectrometry'. PMID: 27644979 [PubMed - as supplied by publisher]

Monitoring the synthesis of biomolecules using mass spectrometry. Philos Trans A Math Phys Eng Sci. 2016 Oct 28;374(2079) Authors: Miyagi M, Kasumov T Abstract The controlled and selective synthesis/clearance of biomolecules is critical for most cellular processes. In most high-throughput 'omics' studies, we measure the static quantities of only one class of biomolecules (e.g. DNA, mRNA, proteins or metabolites). It is, however, important to recognize that biological systems are highly dynamic in which biomolecules are continuously renewed and different classes of biomolecules interact and affect each other's production/clearance. Therefore, it is necessary to measure the turnover of diverse classes of biomolecules to understand the dynamic nature of biological systems. Herein, we explain why the kinetic analysis of a diverse range of biomolecules is important and how such an analysis can be done. We argue that heavy water ((2)H2O) could be a universal tracer for monitoring the synthesis of biomolecules on a global scale.This article is part of the themed issue 'Quantitative mass spectrometry'. PMID: 27644976 [PubMed - as supplied by publisher]

Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation. Philos Trans A Math Phys Eng Sci. 2016 Oct 28;374(2079) Authors: Wang J, Westenskow PD, Fang M, Friedlander M, Siuzdak G Abstract Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic 'fingerprint' of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all-trans-retinal and its toxic end-product N-retinyl-N-retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation.This article is part of the themed issue 'Quantitative mass spectrometry'. PMID: 27644974 [PubMed - as supplied by publisher]

Mass spectrometry as a quantitative tool in plant metabolomics. Philos Trans A Math Phys Eng Sci. 2016 Oct 28;374(2079) Authors: Jorge TF, Mata AT, António C Abstract Metabolomics is a research field used to acquire comprehensive information on the composition of a metabolite pool to provide a functional screen of the cellular state. Studies of the plant metabolome include the analysis of a wide range of chemical species with very diverse physico-chemical properties, and therefore powerful analytical tools are required for the separation, characterization and quantification of this vast compound diversity present in plant matrices. In this review, challenges in the use of mass spectrometry (MS) as a quantitative tool in plant metabolomics experiments are discussed, and important criteria for the development and validation of MS-based analytical methods provided.This article is part of the themed issue 'Quantitative mass spectrometry'. PMID: 27644967 [PubMed - as supplied by publisher]

Increasing rigor in NMR-based metabolomics through validated and open source tools. Curr Opin Biotechnol. 2016 Sep 16;43:56-61 Authors: Eghbalnia HR, Romero PR, Westler WM, Baskaran K, Ulrich EL, Markley JL Abstract The metabolome, the collection of small molecules associated with an organism, is a growing subject of inquiry, with the data utilized for data-intensive systems biology, disease diagnostics, biomarker discovery, and the broader characterization of small molecules in mixtures. Owing to their close proximity to the functional endpoints that govern an organism's phenotype, metabolites are highly informative about functional states. The field of metabolomics identifies and quantifies endogenous and exogenous metabolites in biological samples. Information acquired from nuclear magnetic spectroscopy (NMR), mass spectrometry (MS), and the published literature, as processed by statistical approaches, are driving increasingly wider applications of metabolomics. This review focuses on the role of databases and software tools in advancing the rigor, robustness, reproducibility, and validation of metabolomics studies. PMID: 27643760 [PubMed - as supplied by publisher]

TB or not TB? Improving the understanding and diagnosis of tuberculosis through metabolomics. Biomark Med. 2016 Sep 19; Authors: Loots DT PMID: 27643758 [PubMed - as supplied by publisher]

OS 08-06 METABOLOMIC ANALYSIS OF A MOUSE MODEL OF PREECLAMPSIA INDUCED BY OVERPRODUCING sFlt-1. J Hypertens. 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e69 Authors: Sato E, Tsunokuni Y, Fushima T, Kaneko M, Saito R, Sekimoto A, Saigusa D, Ito S, Sato H, Takahashi N Abstract OBJECTIVE: Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria, and is often associated with fetal growth restriction (FGR). PE is a leading cause of maternal morbidity and mortality. Although alterations in circulating angiogenic factors are pathogenic, the details of pathological mechanisms of PE remain to be elucidated. We investigated changes in metabolites in a mouse model of PE induced by overproducing soluble fms-like tyrosine kinase 1 (sFlt-1) to elucidate the pathological conditions of PE by metabolomics analysis. DESIGN AND METHOD: Recombinant adenovirus to overproduce sFlt-1 was administered to mice (C57BL/6) on 8.5 days post-coitum (dpc) to make PE model. Plasma and placenta samples were harvested at 12.5 dpc for metabolomics analysis by LC-MS and for gene expression analysis. BeWo cells were used to evaluate gene expressions in PE conditions. RESULTS: Blood pressure of a mouse model of PE was significantly increased, and the fetal weight was significantly decreased. Metabolomic analysis revealed that plasma and placental carnitine and acylcarnitines were significantly higher in PE model mice than controls. The mRNA expression of an organic cation transporter (OCTN2), a transporter of carnitines, was significantly increased in placentae from PE model mice and BeWo cells cultured in hypoxic condition. CONCLUSIONS: The difference of carnitine and acylcarnitnes in placenta may contribute to pathological conditions of PE and FGR associated with PE. PMID: 27643351 [PubMed - as supplied by publisher]

Subcellular reprogramming of metabolism during cold acclimation in Arabidopsis thaliana. Plant Cell Environ. 2016 Sep 19; Authors: Hoermiller II, Naegele T, Augustin H, Stutz S, Weckwerth W, Heyer AG Abstract Metabolite changes in plant leaves during exposure to low temperatures involve re-allocation of a large number of metabolites between sub-cellular compartments. Therefore, metabolite determination at the whole cell level may be insufficient for interpretation of the functional significance of cellular compounds. To investigate the cold-induced metabolite dynamics at the level of individual sub-cellular compartments, an integrative platform was developed that combines quantitative metabolite profiling by GC-MS with the non-aqueous fractionation technique allowing separation of cytosol, vacuole and the plastidial compartment. Two mutants of Arabidopsis thaliana representing antipodes in the diversion of carbohydrate metabolism between sucrose and starch were compared to Col-0 wildtype before and after cold acclimation to investigate interactions of cold acclimation with subcellular re-programming of metabolism. A multivariate analysis of the data set revealed dominant effects of compartmentation on metabolite concentrations that were modulated by environmental condition and genetic determinants. While for both, the starchless mutant of plastidial phospho-gluco mutase (pgm) and a mutant defective in sucrose-phosphate synthase A1, metabolic constraints, especially at low temperature, could be uncovered based on subcellularly resolved metabolite profiles, only pgm had lowered freezing tolerance. Metabolic profiles of pgm point to redox imbalance as a possible reason for reduced cold acclimation capacity. PMID: 27642699 [PubMed - as supplied by publisher]

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity. Metabolomics. 2016 Apr;12(4) Authors: Wali S, Gupta R, Yu JJ, Mfuh A, Gao X, Guentzel MN, Chambers JP, Abu Bakar S, Zhong G, Arulanandam BP Abstract INTRODUCTION: Chlamydia trachomatis (Ct), is the leading cause of sexually transmitted infections worldwide. Host transcriptomic- or proteomic profiling studies have identified key molecules involved in establishment of Ct infection or the generation of anti Ct-immunity. However, the contribution of the host metabolome is not known. OBJECTIVES: The objective of this study was to determine the contribution of host metabolites in genital Ct infection. METHODS: We used high-performance liquid chromatography-mass spectrometry, and mapped lipid profiles in genital swabs obtained from female guinea pigs at days 3, 9, 15, 30 and 65 post Ct serovar D intravaginal infection. RESULTS: Across all time points assessed, 13 distinct lipid species including choline, ethanolamine and glycerol were detected. Amongst these metabolites, phosphatidylcholine (PC) was the predominant phospholipid detected from animals actively shedding bacteria i.e., at 3, 9, and 15 days post infection. However, at days 30 and 65 when the animals had cleared the infection, PC was observed to be decreased compared to previous time points. Mass spectrometry analyses of PC produced in guinea pigs (in vivo) and 104C1 guinea pig cell line (in vitro) revealed distinct PC species following Ct D infection. Amongst these, PC 16:0/18:1 was significantly upregulated following Ct D infection (p < 0.05, >twofold change) in vivo and in vitro infection models investigated in this report. Exogenous addition of PC 16:0/18:1 resulted in significant increase in Ct D in Hela 229 cells. CONCLUSION: This study demonstrates a role for host metabolite, PC 16:0/18:1 in regulating genital Ct infection in vivo and in vitro. PMID: 27642272 [PubMed - as supplied by publisher]

Metabolomics enables precision medicine: "A White Paper, Community Perspective". Metabolomics. 2016;12(10):149 Authors: Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmüller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R, for “Precision Medicine and Pharmacometabolomics Task Group”-Metabolomics Society Initiative Abstract INTRODUCTION BACKGROUND TO METABOLOMICS: Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person's metabolic state provides a close representation of that individual's overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates. OBJECTIVES OF WHITE PAPER—EXPECTED TREATMENT OUTCOMES AND METABOLOMICS ENABLING TOOL FOR PRECISION MEDICINE: We anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject's response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers, diabetes and a range of pathologies. A series of ground breaking studies supported by National Institute of Health (NIH) through the Pharmacometabolomics Research Network and its partnership with the Pharmacogenomics Research Network illustrate how a patient's metabotype at baseline, prior to treatment, during treatment, and post-treatment, can inform about treatment outcomes and variations in responsiveness to drugs (e.g., statins, antidepressants, antihypertensives and antiplatelet therapies). These studies along with several others also exemplify how metabolomics data can complement and inform genetic data in defining ethnic, sex, and gender basis for variation in responses to treatment, which illustrates how pharmacometabolomics and pharmacogenomics are complementary and powerful tools for precision medicine. CONCLUSIONS KEY SCIENTIFIC CONCEPTS AND RECOMMENDATIONS FOR PRECISION MEDICINE: Our metabolomics community believes that inclusion of metabolomics data in precision medicine initiatives is timely and will provide an extremely valuable layer of data that compliments and informs other data obtained by these important initiatives. Our Metabolomics Society, through its "Precision Medicine and Pharmacometabolomics Task Group", with input from our metabolomics community at large, has developed this White Paper where we discuss the value and approaches for including metabolomics data in large precision medicine initiatives. This White Paper offers recommendations for the selection of state of-the-art metabolomics platforms and approaches that offer the widest biochemical coverage, considers critical sample collection and preservation, as well as standardization of measurements, among other important topics. We anticipate that our metabolomics community will have representation in large precision medicine initiatives to provide input with regard to sample acquisition/preservation, selection of optimal omics technologies, and key issues regarding data collection, interpretation, and dissemination. We strongly recommend the collection and biobanking of samples for precision medicine initiatives that will take into consideration needs for large-scale metabolic phenotyping studies. PMID: 27642271 [PubMed - as supplied by publisher]

Related Articles Molecular candidates for early-stage flower-to-fruit transition in stenospermocarpic table grape (Vitis vinifera L.) inflorescences ascribed by differential transcriptome and metabolome profiles. Plant Sci. 2016 Mar;244:40-56 Authors: Domingos S, Fino J, Paulo OS, Oliveira CM, Goulao LF Abstract Flower-to-fruit transition depends of nutrient availability and regulation at the molecular level by sugar and hormone signalling crosstalk. However, in most species, the identities of fruit initiation regulators and their targets are largely unknown. To ascertain the main pathways involved in stenospermocarpic table grape fruit set, comprehensive transcriptional and metabolomic analyses were conducted specifically targeting the early phase of this developmental stage in 'Thompson Seedless'. The high-throughput analyses performed disclosed the involvement of 496 differentially expressed genes and 28 differently accumulated metabolites in the sampled inflorescences. Our data show broad transcriptome reprogramming of molecule transporters, globally down-regulating gene expression, and suggest that regulation of sugar- and hormone-mediated pathways determines the downstream activation of berry development. The most affected gene was the SWEET14 sugar transporter. Hormone-related transcription changes were observed associated with increased indole-3-acetic acid, stimulation of ethylene and gibberellin metabolisms and cytokinin degradation, and regulation of MADS-box and AP2-like ethylene-responsive transcription factor expression. Secondary metabolism, the most representative biological process at transcriptome level, was predominantly repressed. The results add to the knowledge of molecular events occurring in grapevine inflorescence fruit set and provide a list of candidates, paving the way for genetic manipulation aimed at model research and plant breeding. PMID: 26810452 [PubMed - indexed for MEDLINE]

Related Articles Survey on the tiered approach for Japanese bioanalysts operated by Japan bioanalysis forum DG2014-09. Bioanalysis. 2016;8(2):93-8 Authors: Niwa M, Koseki N, Hashimoto Y, Mayumi T, Nishimura N, Satsukawa M, Uchimura T, Yasuda Y, Yokoi H PMID: 26653036 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling and in vitro assessment of anthelmintic fractions of Picria fel-terrae Lour. Int J Parasitol Drugs Drug Resist. 2016 Aug 26;6(3):171-178 Authors: Kumarasingha R, Karpe AV, Preston S, Yeo TC, Lim DS, Tu CL, Luu J, Simpson KJ, Shaw JM, Gasser RB, Beale DJ, Morrison PD, Palombo EA, Boag PR Abstract Anthelmintic resistance is widespread in gastrointestinal nematode populations, such that there is a consistent need to search for new anthelmintics. However, the cost of screening for new compounds is high and has a very low success rate. Using the knowledge of traditional healers from Borneo Rainforests (Sarawak, Malaysia), we have previously shown that some traditional medicinal plants are a rich source of potential new anthelmintic drug candidates. In this study, Picria fel-terrae Lour. plant extract, which has previously shown promising anthelmintic activities, was fractionated via the use of a solid phase extraction cartridge and each isolated fraction was then tested on free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. We found that a single fraction was enriched for nematocidal activity, killing ≥90% of C. elegans adults and inhibiting the motility of exsheathed L3 of H. contortus, while having minimal cytotoxic activity in mammalian cell culture. Metabolic profiling and chemometric analysis of the effective fraction indicated medium chained fatty acids and phenolic acids were highly represented. PMID: 27639945 [PubMed - as supplied by publisher]

Related Articles Branched chain amino acid metabolic reprogramming in heart failure. Biochim Biophys Acta. 2016 Sep 14; Authors: Sun H, Wang Y Abstract Metabolic remodeling is a hall-mark of cardiac maturation and pathology. The switch of substrate utilization from glucose to fatty acid is observed during post-natal maturation period in developing heart, but the process is reversed from fatty acids to glucose in the failing hearts across different clinic and experimental models. Majority of the current investigations have been focusing on the regulatory mechanism and functional impact of this metabolic reprogramming involving fatty acids and carbohydrates. Recent progress in metabolomics and transcriptomic analysis, however, revealed another significant remodeled metabolic branch associated with cardiac development and disease, i.e. Branched-Chain Amino Acid (BCAA) catabolism. These findings have established BCAA catabolic deficiency as a novel metabolic feature in failing hearts with potentially significant impact on the progression of pathological remodeling and dysfunction. In this review, we will evaluate the current evidence and potential implication of these discoveries in the context of heart diseases and novel therapies. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz. PMID: 27639835 [PubMed - as supplied by publisher]

Urinary exposure marker discovery for toxicants using ultra-high pressure liquid chromatography coupled with Orbitrap high resolution mass spectrometry and three untargeted metabolomics approaches. Anal Chim Acta. 2016 Oct 5;939:73-83 Authors: Hsu JY, Hsu JF, Chen YR, Shih CL, Hsu YS, Chen YJ, Tsai SH, Liao PC Abstract Human biomonitoring is the assessment of actual internal contamination of chemicals by measuring exposure markers, chemicals or their metabolites, in human urine, blood, serum, and other body fluids. However, the metabolism of chemicals within an organism is extremely complex. Therefore, the identification of metabolites is often difficult and laborious. Several untargeted metabolomics methods have been developed to perform objective searching/filtering of accurate-mass-based LC-MS data to facilitate metabolite identification. In this study, three metabolomics data processing approaches were used for chemical exposure marker discovery in urine with an LTQ-Orbitrap high-resolution mass spectrometry (HRMS) dataset; di-isononyl phthalate (DINP) was used as an example. The data processing techniques included the SMAIT, mass defect filtering (MDF), and XCMS Online. Sixteen, 83, and 139 probable DINP metabolite signals were obtained using the SMAIT, MDF, and XCMS procedures, respectively. Fourteen probable metabolite signals mined simultaneously by the three metabolomics approaches were confirmed as DINP metabolites by structural information provided by LC-MS/MS. Among them, 13 probable metabolite signals were validated as exposure-related markers in a rat model. Six (m/z 319.155, 361.127, 373.126, 389.157, 437.112 and 443.130) of the 13 exposure-related DINP metabolite signals have not previously been reported in the literature. Our data indicate that SMAIT provided an efficient method to discover effectively and systematically urinary exposure markers of toxicant. The DINP metabolism information can provide valuable information for further investigations of DINP toxicity, toxicokinetics, exposure assessment, and human health effects. PMID: 27639145 [PubMed - as supplied by publisher]

Multidimensional NMR approaches towards highly resolved, sensitive and high-throughput quantitative metabolomics. Curr Opin Biotechnol. 2016 Sep 13;43:49-55 Authors: Marchand J, Martineau E, Guitton Y, Dervilly-Pinel G, Giraudeau P Abstract Multi-dimensional NMR is an appealing approach for dealing with the challenging complexity of biological samples in metabolomics. This article describes how spectroscopists have recently challenged their imagination in order to make 2D NMR a powerful tool for quantitative metabolomics, based on innovative pulse sequences combined with meticulous analytical chemistry approaches. Clever time-saving strategies have also been explored to make 2D NMR a high-throughput tool for metabolomics, relying on alternative data acquisition schemes such as ultrafast NMR. Currently, much work is aimed at drastically boosting the NMR sensitivity thanks to hyperpolarisation techniques, which have been used in combination with fast acquisition methods and could greatly expand the application potential of NMR metabolomics. PMID: 27639136 [PubMed - as supplied by publisher]

Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease. J Neurosci Res. 2016 Nov;94(11):1094-107 Authors: Weinstock NI, Wrabetz L, Feltri ML, Shin D Abstract Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression when performed presymptomatically but carries a significant risk of morbidity and mortality. Accurate presymptomatic diagnosis is therefore critical to facilitate the efficacy of existing transplant approaches and to avoid unnecessary treatment of children who will not develop KD. Unfortunately, current diagnostic criteria, including GALC activity, genetic analysis, and psychosine measurement, are insufficient for secure presymptomatic diagnosis. This study performs a global metabolomic analysis to identify pathogenetic metabolic pathways and novel biomarkers implicated in the authentic mouse model of KD known as twitcher. At a time point before onset of signs of disease, twitcher hindbrains had metabolic profiles similar to WT, with the exception of a decrease in metabolites related to glucose energy metabolism. Many metabolic pathways were altered after early signs of disease in the twitcher, including decreased phospholipid turnover, restricted mitochondrial metabolism of branched-chain amino acids, increased inflammation, and changes in neurotransmitter metabolism and osmolytes. Hypoxanthine, a purine derivative, is increased before signs of disease appear, suggesting its potential as a biomarker for early diagnosis of KD. Additionally, given the early changes in glucose metabolism in the pathogenesis of KD, diagnostic modalities that report metabolic function, such as positron emission tomography, may be useful in KD. © 2016 Wiley Periodicals, Inc. PMID: 27638595 [PubMed - in process]