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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 2018/08/17PubMed 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.

Metabolic and immunological responses of male and female New Zealand Greenshell™ mussels (Perna canaliculus) infected with Vibrio sp. J Invertebr Pathol. 2018 Aug 12;: Authors: Nguyen TV, Alfaro AC, Merien F, Young T, Grandiosa R Abstract Massive mortalities due to pathogens are routinely reported in bivalve cultivation that have significant economic consequences for the global aquaculture industry. However, host-pathogen interactions and infection mechanisms that mediate these interactions are poorly understood. In addition, gender-specific immunological responses have been reported for some species, but the reasons for such differences have not been elucidated. In this study, we used a GC/MS-based metabolomics platform and flow cytometry approach to characterize metabolic and immunological responses in haemolymph of male and female mussels (Perna canaliculus) experimentally infected with Vibrio sp. Sex-based differences in immunological responses were identified, with male mussels displaying higher mortality, oxidative stress and apoptosis after pathogen exposure. However, central metabolic processes appeared to be similar between sexes at 24 h post injection with Vibrio sp. DO1. Significant alterations in relative levels of 37 metabolites were detected between infected and uninfected mussels. These metabolites are involved in major perturbations on the host's innate immune system. In addition, there were alterations of seven metabolites in profiles of mussels sampled on the second day and mussels that survived six days after exposure. These metabolites include itaconic acid, isoleucine, phenylalanine, creatinine, malonic acid, glutaric acid and hydroxyproline. Among these, itaconic acid has the potential to be an important biomarker for Vibrio sp. DO1 infection. These findings provide new insights on the mechanistic relationship between a bivalve host and a pathogenic bacterium and highlight the need to consider host sex as a biological variable in future immunological studies. PMID: 30110610 [PubMed - as supplied by publisher]

The fecal microbiome and metabolome differs between dogs fed Bones and Raw Food (BARF) diets and dogs fed commercial diets. PLoS One. 2018;13(8):e0201279 Authors: Schmidt M, Unterer S, Suchodolski JS, Honneffer JB, Guard BC, Lidbury JA, Steiner JM, Fritz J, Kölle P Abstract INTRODUCTION: Feeding a Bones and Raw Food (BARF) diet has become an increasing trend in canine nutrition. Bones and Raw Food diets contain a high amount of animal components like meat, offal, and raw meaty bones, combined with comparatively small amounts of plant ingredients like vegetables and fruits as well as different sorts of oil and supplements. While many studies have focused on transmission of pathogens via contaminated meat and on nutritional imbalances, only few studies have evaluated the effect of BARF diets on the fecal microbiome and metabolome. The aim of the study was to investigate differences in the fecal microbiome and the metabolome between dogs on a BARF diet and dogs on a commercial diet (canned and dry dog food). METHODS: Naturally passed fecal samples were obtained from 27 BARF and 19 commercially fed dogs. Differences in crude protein, fat, fiber, and NFE (Nitrogen-Free Extract) between diets were calculated with a scientific nutrient database. The fecal microbiota was analyzed by 16S rRNA gene sequencing and quantitative PCR assays. The fecal metabolome was analyzed in 10 BARF and 9 commercially fed dogs via untargeted metabolomics approach. RESULTS: Dogs in the BARF group were fed a significantly higher amount of protein and fat and significantly lower amount of NFE and fiber. There was no significant difference in alpha-diversity measures between diet groups. Analysis of similarity (ANOSIM) revealed a significant difference in beta-diversity (p < 0.01) between both groups. Linear discriminant analysis effect size (LefSe) showed a higher abundance of Lactobacillales, Enterobacteriaceae, Fusobacterium and, Clostridium in the BARF group while conventionally fed dogs had a higher abundance of Clostridiaceae, Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae. The qPCR assays revealed significantly higher abundance of Escherichia coli (E. coli) and Clostridium (C.). perfringens and an increased Dysbiosis Index in the BARF group. Principal component analysis (PCA) plots of metabolomics data showed clustering between diet groups. Random forest analysis showed differences in the abundance of various components, including increased 4-hydroxybutryric acid (GBH) and 4-aminobutyric acid (GABA) in the BARF group. Based on univariate statistics, several metabolites were significantly different between diet groups, but lost significance after adjusting for multiple comparison. No differences were found in fecal bile acid concentrations, but the BARF group had a higher fecal concentration of cholesterol in their feces compared to conventionally fed dogs. CONCLUSION: Microbial communities and metabolome vary significantly between BARF and commercially fed dogs. PMID: 30110340 [PubMed - in process]

Related Articles PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold. Cell Mol Life Sci. 2018 Aug 14;: Authors: Madio B, Peigneur S, Chin YKY, Hamilton BR, Henriques ST, Smith JJ, Cristofori-Armstrong B, Dekan Z, Boughton BA, Alewood PF, Tytgat J, King GF, Undheim EAB Abstract Sea anemone venoms have long been recognized as a rich source of peptides with interesting pharmacological and structural properties, but they still contain many uncharacterized bioactive compounds. Here we report the discovery, three-dimensional structure, activity, tissue localization, and putative function of a novel sea anemone peptide toxin that constitutes a new, sixth type of voltage-gated potassium channel (KV) toxin from sea anemones. Comprised of just 17 residues, κ-actitoxin-Ate1a (Ate1a) is the shortest sea anemone toxin reported to date, and it adopts a novel three-dimensional structure that we have named the Proline-Hinged Asymmetric β-hairpin (PHAB) fold. Mass spectrometry imaging and bioassays suggest that Ate1a serves a primarily predatory function by immobilising prey, and we show this is achieved through inhibition of Shaker-type KV channels. Ate1a is encoded as a multi-domain precursor protein that yields multiple identical mature peptides, which likely evolved by multiple domain duplication events in an actinioidean ancestor. Despite this ancient evolutionary history, the PHAB-encoding gene family exhibits remarkable sequence conservation in the mature peptide domains. We demonstrate that this conservation is likely due to intra-gene concerted evolution, which has to our knowledge not previously been reported for toxin genes. We propose that the concerted evolution of toxin domains provides a hitherto unrecognised way to circumvent the effects of the costly evolutionary arms race considered to drive toxin gene evolution by ensuring efficient secretion of ecologically important predatory toxins. PMID: 30109357 [PubMed - as supplied by publisher]

Related Articles Increased glutamine anabolism sensitizes non-small cell lung cancer to gefitinib treatment. Cell Death Discov. 2018;5:24 Authors: Wang L, Peng W, Wu T, Deng P, Zhao YL Abstract To better understand the resistance mechanism of non-small cell lung cancers (NSCLCs) to gefitinib, the metabolic profiles of gefitinib-resistant A549 cells and gefitinib-sensitive PC-9 cells were analyzed with a metabolomics analytical platform. A549 and PC-9 cells exhibited significant differences in the levels of glutamine-related metabolites. After gefitinib treatment, the glutamine level decreased in A549 cells but showed no change in PC-9 cells. The glutamine consumed by A549 cells was used to generate ATP and glutathione (GSH). As glutamine utilization was suppressed in gefitinib-treated PC-9 cells, the resulting ATP shortage and ROS accumulation led to cell death. The difference in glutamine metabolism was caused by differential changes in the levels of glutamine synthetase (GS, encoded by glutamate-ammonia ligase (GLUL)). GLUL expression was upregulated in gefitinib-sensitive cells, but it was either absent from gefitinib-resistant cells or no significant change was observed in the gefitinib-treated cells. GLUL overexpression in A549 cells significant sensitized them to gefitinib and decreased their invasive capacity. Conversely, knockout GS in PC-9 cells reduced gefitinib sensitivity and enhanced metastasis. Furthermore, the continuous exposure of gefitinib-sensitive HCC827 cells to gefitinib created gefitinib-resistant (GR) HCC827 cells, which exhibited a GLUL deletion and resistance to gefitinib. Thus, GLUL plays a vital role in determining the sensitivity of NSCLCs to gefitinib. Elevated GS levels mediate increased glutamine anabolism, and this novel mechanism sensitizes NSCLCs to gefitinib. The inhibition of glutamine utilization may serve as a potential therapeutic strategy to overcome gefitinib resistance in the clinic. PMID: 30109143 [PubMed]

Related Articles Best practice data life cycle approaches for the life sciences. F1000Res. 2017;6:1618 Authors: Griffin PC, Khadake J, LeMay KS, Lewis SE, Orchard S, Pask A, Pope B, Roessner U, Russell K, Seemann T, Treloar A, Tyagi S, Christiansen JH, Dayalan S, Gladman S, Hangartner SB, Hayden HL, Ho WWH, Keeble-Gagnère G, Korhonen PK, Neish P, Prestes PR, Richardson MF, Watson-Haigh NS, Wyres KL, Young ND, Schneider MV Abstract Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. PMID: 30109017 [PubMed - in process]

Related Articles Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine production. Sci Rep. 2018 Aug 14;8(1):12154 Authors: Rodrigues FAP, Santos ADDC, de Medeiros PHQS, Prata MMG, Santos TCS, da Silva JA, Brito GAC, Dos Santos AA, Silveira ER, Lima AÂM, Havt A Abstract Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols. 1H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane. PMID: 30108263 [PubMed - in process]

Related Articles Natural genetic variation in C. elegans identified genomic loci controlling metabolite levels. Genome Res. 2018 Aug 14;: Authors: Gao AW, Sterken MG, Uit de Bos J, van Creij J, Kamble R, Snoek BL, Kammenga JE, Houtkooper RH Abstract Metabolic homeostasis is sustained by complex biological networks that respond to nutrient availability. Genetic and environmental factors may disrupt this equilibrium, leading to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we performed quantitative genetic analysis using a population of 199 recombinant inbred lines (RILs) in the nematode Caenorhabditis elegans We focused on the genomic regions that control metabolite levels by measuring fatty acid (FA) and amino acid (AA) composition in the RILs using targeted metabolomics. The genetically diverse RILs showed a large variation in their FA and AA levels with a heritability ranging from 32% to 82%. We detected strongly co-correlated metabolite clusters and 36 significant metabolite QTL (mQTL). We focused on mQTL displaying highly significant linkage and heritability, including an mQTL for the FA C14:1 on Chromosome I, and another mQTL for the FA C18:2 on Chromosome IV. Using introgression lines (ILs), we were able to narrow down both mQTL to a 1.4-Mbp and a 3.6-Mbp region, respectively. RNAi-based screening focusing on the Chromosome I mQTL identified several candidate genes for the C14:1 mQTL, including lagr-1, Y87G2A.2, nhr-265, nhr-276, and nhr-81 Overall, this systems approach provides us with a powerful platform to study the genetic basis of C. elegans metabolism. Furthermore, it allows us to investigate interventions such as nutrients and stresses that maintain or disturb the regulatory network controlling metabolic homeostasis, and identify gene-by-environment interactions. PMID: 30108180 [PubMed - as supplied by publisher]

Related Articles Biochemical and Epigenetic Insights into L-2-Hydroxyglutarate, a Potential Therapeutic Target in Renal Cancer. Clin Cancer Res. 2018 Aug 14;: Authors: Shelar S, Shim EH, Brinkley G, Kundu A, Carobbio F, Poston T, Tan J, Parekh V, Benson D, Crossman DK, Buckhaults PJ, Rakheja D, Kirkman R, Sato Y, Ogawa S, Dutta S, Velu SE, Emberley E, Pan A, Chen J, Huang T, Absher D, Becker A, Kunick C, Sudarshan S Abstract PURPOSE: Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC) is due in part to reduced expression of L-2-HG dehydrogenase (L2HGDH). However, the contribution of L-2-HG to renal carcinogenesis and insight into the biochemistry and targets of this small molecule remains to be elucidated. EXPERIMENTAL DESIGN: Genetic and pharmacologic approaches to modulate L-2-HG levels were assessed for effects onin vitro and in vivophenotypes. Metabolomics was used to dissect the biochemical mechanisms that promote L-2-HG accumulation in RCC cells. Transcriptomic analysis was utilized to identify relevant targets of L-2-HG. Finally, bioinformatic and metabolomic analyses were used to assess the L-2-HG/L2HGDH axis as a function of patient outcome and cancer progression. RESULTS: L2HGDH suppresses both in vitrocell migration and in vivotumor growth and these effects are mediated by L2HGDH's catalytic activity. Biochemical studies indicate that glutamine is the predominant carbon source for L-2-HG via the activity of malate dehydrogenase 2 (MDH2). Inhibition of the glutamine-MDH2 axis suppresses in vitrophenotypes in a L-2-HG dependent manner. Moreover, in vivogrowth of RCC cells with basal elevation of L-2-HG is suppressed by glutaminase inhibition. Transcriptomic and functional analyses demonstrate that the histone demethylase KDM6A is a target of L-2-HG in RCC. Finally, increased L-2-HG levels, L2HGDHcopy loss, and lower L2HGDH expression are associated with tumor progression and/or worsened prognosis in RCC patients. CONCLUSIONS: Collectively, our studies provide biochemical and mechanistic insight into the biology of this small molecule and provide new opportunities for treating L-2-HG driven kidney cancers. PMID: 30108105 [PubMed - as supplied by publisher]

Related Articles Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging. Placenta. 2017 12;60 Suppl 1:S67-S72 Authors: Burnum-Johnson KE, Baker ES, Metz TO Abstract Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes. PMID: 28392013 [PubMed - indexed for MEDLINE]

Related Articles Automated Detection of Natural Halogenated Compounds from LC-MS Profiles-Application to the Isolation of Bioactive Chlorinated Compounds from Marine-Derived Fungi. Anal Chem. 2016 09 20;88(18):9143-50 Authors: Roullier C, Guitton Y, Valery M, Amand S, Prado S, Robiou du Pont T, Grovel O, Pouchus YF Abstract A collection of culture extracts obtained from several marine-derived fungal strains collected on the French Atlantic coast was investigated by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) in order to prospect for halogenated compounds and to identify potentially new ones. To achieve a fast, automated, and efficient data analysis, a bioinformatics tool named MeHaloCoA (Marine Halogenated Compound Analysis) was developed and included into R. After extraction of all the peaks from the metabolic fingerprints and their associated mass spectra, a mathematical filter based on mass isotopic profiles allowed the selective detection of halogenated (Cl and Br) molecules. Integrating MeHaloCoA into a dereplication approach allowed the identification of known and new halogenated compounds in a competitive amount of time. Subsequent targeted purification led to the isolation of several chlorinated metabolites, including two new natural products with bioactive potential, griseophenone I and chlorogriseofulvin, from a marine-derived Penicillium canescens strain. PMID: 27537349 [PubMed - indexed for MEDLINE]

Related Articles Development and Application of Ultra-Performance Liquid Chromatography-TOF MS for Precision Large Scale Urinary Metabolic Phenotyping. Anal Chem. 2016 09 20;88(18):9004-13 Authors: Lewis MR, Pearce JT, Spagou K, Green M, Dona AC, Yuen AH, David M, Berry DJ, Chappell K, Horneffer-van der Sluis V, Shaw R, Lovestone S, Elliott P, Shockcor J, Lindon JC, Cloarec O, Takats Z, Holmes E, Nicholson JK Abstract To better understand the molecular mechanisms underpinning physiological variation in human populations, metabolic phenotyping approaches are increasingly being applied to studies involving hundreds and thousands of biofluid samples. Hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) has become a fundamental tool for this purpose. However, the seemingly inevitable need to analyze large studies in multiple analytical batches for UPLC-MS analysis poses a challenge to data quality which has been recognized in the field. Herein, we describe in detail a fit-for-purpose UPLC-MS platform, method set, and sample analysis workflow, capable of sustained analysis on an industrial scale and allowing batch-free operation for large studies. Using complementary reversed-phase chromatography (RPC) and hydrophilic interaction liquid chromatography (HILIC) together with high resolution orthogonal acceleration time-of-flight mass spectrometry (oaTOF-MS), exceptional measurement precision is exemplified with independent epidemiological sample sets of approximately 650 and 1000 participant samples. Evaluation of molecular reference targets in repeated injections of pooled quality control (QC) samples distributed throughout each experiment demonstrates a mean retention time relative standard deviation (RSD) of <0.3% across all assays in both studies and a mean peak area RSD of <15% in the raw data. To more globally assess the quality of the profiling data, untargeted feature extraction was performed followed by data filtration according to feature intensity response to QC sample dilution. Analysis of the remaining features within the repeated QC sample measurements demonstrated median peak area RSD values of <20% for the RPC assays and <25% for the HILIC assays. These values represent the quality of the raw data, as no normalization or feature-specific intensity correction was applied. While the data in each experiment was acquired in a single continuous batch, instances of minor time-dependent intensity drift were observed, highlighting the utility of data correction techniques despite reducing the dependency on them for generating high quality data. These results demonstrate that the platform and methodology presented herein is fit-for-use in large scale metabolic phenotyping studies, challenging the assertion that such screening is inherently limited by batch effects. Details of the pipeline used to generate high quality raw data and mitigate the need for batch correction are provided. PMID: 27479709 [PubMed - indexed for MEDLINE]

21 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 2018/08/15PubMed 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.

21 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 2018/08/15PubMed 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.

19 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 2018/08/14PubMed 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.

Related Articles Non-targeted metabolomics reveals alterations in liver and plasma of gilt-head bream exposed to oxybenzone. Chemosphere. 2018 Aug 04;211:624-631 Authors: Ziarrusta H, Mijangos L, Picart-Armada S, Irazola M, Perera-Lluna A, Usobiaga A, Prieto A, Etxebarria N, Olivares M, Zuloaga O Abstract The extensive use of the organic UV filter oxybenzone has led to its ubiquitous occurrence in the aquatic environment, causing an ecotoxicological risk to biota. Although some studies reported adverse effects, such as reproductive toxicity, further research needs to be done in order to assess its molecular effects and mechanism of action. Therefore, in the present work, we investigated metabolic perturbations in juvenile gilt-head bream (Sparus aurata) exposed over 14 days via the water to oxybenzone (50 mg/L). The non-targeted analysis of brain, liver and plasma extracts was performed by means of UHPLC-qOrbitrap MS in positive and negative modes with both C18 and HILIC separation. Although there was no mortality or alterations in general physiological parameters during the experiment, and the metabolic profile of brain was not affected, the results of this study showed that oxybenzone could perturb both liver and plasma metabolome. The pathway enrichment suggested that different pathways in lipid metabolism (fatty acid elongation, α-linolenic acid metabolism, biosynthesis of unsaturated fatty acids and fatty acid metabolism) were significantly altered, as well as metabolites involved in phenylalanine and tyrosine metabolism. Overall, these changes are signs of possible oxidative stress and energy metabolism modification. Therefore, this research indicates that oxybenzone has adverse effects beyond the commonly studied hormonal activity, and demonstrates the sensitivity of metabolomics to assess molecular-level effects of emerging contaminants. PMID: 30098557 [PubMed - as supplied by publisher]

Related Articles 8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with stronger metabolic modulator activity. Toxicol In Vitro. 2018 Aug 08;: Authors: Carrageta DF, Dias TR, Jarak I, Alves MG, Oliveira PF, Van der Walt MM, Terre'Blanche G, Monteiro MP, Silva BM Abstract Caffeine is one of the most worldwide consumed methylxanthines. It is well-known for its thermogenic and cell metabolism modulating effects. Based on methylxanthines' chemical structure, 8-(3-phenylpropyl)-1,3,7-triethylxanthine (PTX) is a novel adenosine antagonist with higher receptor affinity than caffeine. Therefore, we hypothesized that PTX metabolic effects could be stronger than those of caffeine. For that purpose, murine 3 T3-L1 cells were cultured in the presence of increasing doses of PTX or caffeine (0.1, 1, 10 and 100 μM) for 24 h. Cytotoxicity was evaluated by reduction of tetrazolium salt (MTT) and lactate dehydrogenase (LDH) release. Cell metabolites released to the culture medium were identified and quantified by proton nuclear magnetic resonance (1H NMR). Cellular oxidative profile was also evaluated. Our results showed that PTX displayed no signs of cytotoxicity at all studied concentrations. When compared with caffeine, PTX increased glucose, pyruvate, and glutamine consumption, as well as lactate, alanine, and acetate production. Additionally, PTX decreased protein oxidation, thus protecting against oxidative stress-induced damage. These results illustrate that PTX is a stronger and less cytotoxic caffeine substitute with potential applications as metabolic modulator and a good candidate for novel drug design. PMID: 30098389 [PubMed - as supplied by publisher]

Related Articles Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain. Neurochem Int. 2018 Aug 09;120:75-86 Authors: Chitturi J, Li Y, Santhakumar V, Kannurpatti SS Abstract Pathophysiology of developmental traumatic brain injury (TBI) is unique due to intrinsic differences in the developing brain. Energy metabolic studies of the brain during early development (P13 to P30) have indicated acute oxidative energy metabolic decreases below 24 h after TBI, which generally recovered by 48 h. However, marked neurodegeneration and altered neural functional connectivity have been observed at later stages into adolescence. As secondary neurodegeneration is most prominent during the first week after TBI in the rat model, we hypothesized that the subacute TBI-metabolome may contain predictive markers of neurodegeneration. Sham and TBI metabolomes were examined at 72 h after a mild to moderate intensity TBI in male Sprague-Dawley rats aged P31. Sensorimotor behavior was assessed at 24, 48 and 72 h after injury, followed by 72-hour postmortem brain removal for metabolomics using Liquid Chromatography/Mass Spectrometry (LC-MS) measurement. Broad TBI-induced metabolomic shifts occurred with relatively higher intensity in the injury-lateralized (ipsilateral) hemisphere. Intensity of metabolomic perturbation correlated with the extent of sensorimotor behavioral deficit. N-acetyl-aspartate (NAA) levels at 72 h after TBI, predicted the extent of neurodegeneration assessed histochemically 7-days post TBI. Results from the multivariate untargeted approach clearly distinguished metabolomic shifts induced by TBI. Several pathways including amino acid, fatty acid and energy metabolism continued to be affected at 72 h after TBI, whose collective effects may determine the overall pathological response after TBI in early development including neurodegeneration. PMID: 30098378 [PubMed - as supplied by publisher]

Related Articles Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and Amino Acid Metabolism in Healthy People. Mol Nutr Food Res. 2018 Aug 11;:e1800583 Authors: Wei R, Ross AB, Su M, Wang J, Guiraud SP, Draper CF, Beaumont M, Jia W, Martin FP Abstract SCOPE: The objective of this study was to develop a new methodology to identify the relationship between dietary patterns and metabolites indicative of food intake and metabolism. METHODS AND RESULTS: Plasma and urine samples from healthy Swiss subjects (n = 89) collected over two time points were analyzed for a panel of host-microbial metabolites using gas chromatography- and liquid chromatography-mass spectrometry. Dietary intake was evaluated using a validated food frequency questionnaire. Dietary pattern clusters and relationships with metabolites were determined using Non-Negative Matrix Factorization (NNMF) and Sparse Generalized Canonical Correlation Analysis (SGCCA). Use of NNMF allowed detection of latent diet clusters in this population, which described a high intake of meat or vegetables. SGCCA associated these clusters to (i) diet-host microbial and lipid associated bile acid metabolism, and (ii) essential amino acid metabolism. CONCLUSION: This novel application of NNMF and SGCCA allowed detection of distinct metabotypes for meat and vegetable dietary patterns in a heterogeneous population. As many of the metabolites associated with meat or vegetable intake are the result of host-microbiota interactions, the results support a role for microbiota mediating the metabolic imprinting of different dietary choices. This article is protected by copyright. All rights reserved. PMID: 30098305 [PubMed - as supplied by publisher]

Related Articles NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells. FEBS J. 2018 Aug 11;: Authors: Becker-Kettern J, Paczia N, Conrotte JF, Zhu C, Fiehn O, Jung PP, Steinmetz LM, Linster CL Abstract NADHX and NADPHX are hydrated and redox inactive forms of the NADH and NADPH cofactors, known to inhibit several dehydrogenases in vitro. A metabolite repair system that is conserved in all domains of life and that comprises the two enzymes NAD(P)HX dehydratase and NAD(P)HX epimerase, allows reconversion of both the S- and R-epimers of NADHX and NADPHX to the normal cofactors. An inherited deficiency in this system has recently been shown to cause severe neurometabolic disease in children. Although evidence for the presence of NAD(P)HX has been obtained in plant and human cells, little is known about the mechanism of formation of these derivatives in vivo and their potential effects on cell metabolism. Here, we show that NAD(P)HX dehydratase deficiency in yeast leads to an important, temperature-dependent NADHX accumulation in quiescent cells with a concomitant depletion of intracellular NAD+ and serine pools. We demonstrate that NADHX potently inhibits the first step of the serine synthesis pathway in yeast. Human cells deficient in the NAD(P)HX dehydratase also accumulated NADHX and showed decreased viability. In addition, those cells consumed more glucose and produced more lactate, potentially indicating impaired mitochondrial function. Our results provide first insights into how NADHX accumulation affects cellular functions and pave the way for a better understanding of the mechanism(s) underlying the rapid and severe neurodegeneration leading to early death in NADHX repair deficient children. This article is protected by copyright. All rights reserved. PMID: 30098110 [PubMed - as supplied by publisher]