PubMed

Related Articles Exploring bacterial interspecific interactions for discovery of novel antimicrobial compounds. Microb Biotechnol. 2017 May 29;: Authors: Tyc O, de Jager VCL, van den Berg M, Gerards S, Janssens TKS, Zaagman N, Kai M, Svatos A, Zweers H, Hordijk C, Besselink H, de Boer W, Garbeva P Abstract Recent studies indicated that the production of secondary metabolites by soil bacteria can be triggered by interspecific interactions. However, little is known to date about interspecific interactions between Gram-positive and Gram-negative bacteria. In this study, we aimed to understand how the interspecific interaction between the Gram-positive Paenibacillus sp. AD87 and the Gram-negative Burkholderia sp. AD24 affects the fitness, gene expression and the production of soluble and volatile secondary metabolites of both bacteria. To obtain better insight into this interaction, transcriptome and metabolome analyses were performed. Our results revealed that the interaction between the two bacteria affected their fitness, gene expression and the production of secondary metabolites. During interaction, the growth of Paenibacillus was not affected, whereas the growth of Burkholderia was inhibited at 48 and 72 h. Transcriptome analysis revealed that the interaction between Burkholderia and Paenibacillus caused significant transcriptional changes in both bacteria as compared to the monocultures. The metabolomic analysis revealed that the interaction increased the production of specific volatile and soluble antimicrobial compounds such as 2,5-bis(1-methylethyl)-pyrazine and an unknown Pederin-like compound. The pyrazine volatile compound produced by Paenibacillus was subjected to bioassays and showed strong inhibitory activity against Burkholderia and a range of plant and human pathogens. Moreover, strong additive antimicrobial effects were observed when soluble extracts from the interacting bacteria were combined with the pure 2,5-bis(1-methylethyl)-pyrazine. The results obtained in this study highlight the importance to explore bacterial interspecific interactions to discover novel secondary metabolites and to perform simultaneously metabolomics of both, soluble and volatile compounds. PMID: 28557379 [PubMed - as supplied by publisher]

Related Articles Characterization of Metabolite Profile in Phyllanthus niruri and Correlation with Bioactivity Elucidated by Nuclear Magnetic Resonance Based Metabolomics. Molecules. 2017 May 30;22(6): Authors: Mediani A, Abas F, Maulidiani M, Khatib A, Tan CP, Ismail IS, Shaari K, Ismail A Abstract Phyllanthus niruri is an important medicinal plant. To standardize the extract and guarantee its maximum benefit, processing methods optimization ought to be amenable and beneficial. Herein, three dried P. niruri samples, air (AD), freeze (FD) and oven (OD), extracted with various ethanol to water ratios (0%, 50%, 70%, 80% and 100%) were evaluated for their metabolite changes using proton nuclear magnetic resonance (¹H-NMR)-based metabolomics approach. The amino acids analysis showed that FD P. niruri exhibited higher content of most amino acids compared to the other dried samples. Based on principal component analysis (PCA), the FD P. niruri extracted with 80% ethanol contained higher amounts of hypophyllanthin and phenolic compounds based on the loading plot. The partial least-square (PLS) results showed that the phytochemicals, including hypophyllanthin, catechin, epicatechin, rutin, quercetin and chlorogenic, caffeic, malic and gallic acids were correlated with antioxidant and α-glucosidase inhibitory activities, which were higher in the FD material extracted with 80% ethanol. This report optimized the effect of drying and ethanol ratios and these findings demonstrate that NMR-based metabolomics was an applicable approach. The FD P. niruri extracted with 80% ethanol can be used as afunctional food ingredient for nutraceutical or in medicinal preparation. PMID: 28556789 [PubMed - in process]

Related Articles Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes. Mol Nutr Food Res. 2017 May 29;: Authors: Df de Mello V, A Lankinen M, Lindström J, Puupponen-Pimiä R, E Laaksonen D, Pihlajamäki J, Lehtonen M, Uusitupa M, Tuomilehto J, Kolehmainen M, Törrönen R, Hanhineva K Abstract SCOPE: Urinary hippuric acid has been proposed as a biomarker for fruit, vegetable and polyphenol consumption. We assessed how serum hippuric acid changes after a bilberry-enriched diet (BB; high anthocyanin intake) and another berry diet including strawberries, raspberries and cloudberries (SRC; lower anthocyanin intake) and how these changes associate with insulin and glucose metabolism. METHODS AND RESULTS: Hippuric acid was measured with LC-QTOF-MS metabolite profiling analysis from fasting serum samples at baseline and after an 8-week intervention in 47 individuals with features of the metabolic syndrome who were randomized to either a BB diet (n = 15), a SRC diet (n = 20) or a control diet (n = 12). Fasting serum hippuric acid increased significantly (3.5-fold, p = 0.001) only in the BB group and correlated with changes in fasting plasma glucose concentration (r = -0.54, p < 0.05) and insulin secretion (r = 0.59, p < 0.05). These associations were confirmed in the Finnish Diabetes Prevention Study (n = 198). CONCLUSION: Fasting serum hippuric acid is increased after consumption of anthocyanin-rich bilberries, and may contribute to the beneficial effect of bilberry consumption through its associations with better glycemic control and β-cell function. This article is protected by copyright. All rights reserved. PMID: 28556578 [PubMed - as supplied by publisher]

Related Articles Demonstration of the utility of biomarkers for dietary intake assessment; proline betaine as an example. Mol Nutr Food Res. 2017 May 28;: Authors: Gibbons H, Michielsen CJR, Rundle M, Frost G, McNulty BA, Nugent AP, Walton J, Flynn A, Gibney MJ, Brennan L Abstract SCOPE: There is a dearth of studies demonstrating the use of dietary biomarkers for determination of food intake. The objective of this study was to develop calibration curves for use in quantifying citrus intakes in an independent cohort. METHODS AND RESULTS: Participants (n = 50) from the NutriTech food-intake study consumed standardized breakfasts for three consecutive days over three consecutive weeks. Orange juice intake decreased over the weeks. Urine samples were analyzed by NMR-spectroscopy and proline betaine was quantified and normalized to osmolality. Calibration curves were developed and used to predict citrus intake in an independent cohort; the Irish National Adult Nutrition Survey (NANS) (n = 565). Proline betaine displayed a dose-response relationship to orange juice intake in 24h and fasting samples (p<0.001). In a test set, predicted orange juice intakes displayed excellent agreement with true intake. There were significant associations between predicted intake measured in 24h and fasting samples and true intake(r = 0.710-0.919). Citrus intakes predicted for the NANS cohort demonstrated good agreement with self-reported intake and this agreement improved following normalization to osmolality. CONCLUSION: The developed calibration curves successfully predicted citrus intakes in an independent cohort. Expansion of this approach to other foods will be important for the development of objective intake measurements. This article is protected by copyright. All rights reserved. PMID: 28556565 [PubMed - as supplied by publisher]

Related Articles Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2017 May 26;: Authors: Arbelaiz A, Azkargorta M, Krawczyk M, Santos-Laso A, Lapitz A, Perugorria MJ, Erice O, Gonzalez E, Jimenez-Agüero R, Lacasta A, Ibarra C, Sanchez-Campos A, Jimeno JP, Lammert F, Milkiewicz P, Marzioni M, Macias RIR, Marin JJG, Patel T, Gores GJ, Martinez I, Elortza F, Falcon-Perez JM, Bujanda L, Banales JM Abstract Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions such as primary sclerosing cholangitis (PSC) are risk factors. Non-invasive differential diagnosis between intrahepatic CCA (iCCA) and hepatocellular carcinoma (HCC) is sometimes difficult. Accurate non-invasive biomarkers for PSC, CCA or HCC are not available. In the search of novel biomarkers, serum extracellular vesicles (EV) were isolated from CCA (n=43), PSC (n=30) or HCC (n=29) patients, and healthy individuals (control, n=32), and their protein content was characterized. By using nanoparticle tracking analysis (NTA), serum EV concentration was found higher in HCC than all the other groups. Round morphology (by transmission electron microscopy), size (∼180 nm diameter by NTA) and markers (CD9, CD63 and CD81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed multiple differentially expressed proteins among groups. Several of these proteins showed high diagnostic values with maximum area under the ROC curve (AUC) of 0.878 for CCA vs control, 0.905 for CCA stage I-I vs control, 0.789 for PSC vs control, 0.806 for PSC non-cirrhotic vs control, 0.796 for CCA vs PSC, 0.956 for CCA stage I-I vs PSC, 0.904 for HCC vs control, and 0.894 for iCCA vs HCC. The proteomic analysis of EV derived from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by normal human cholangiocytes. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release to serum of EV containing some similar human oncogenic proteins. CONCLUSION: novel proteomic signatures found in serum EV of CCA, PSC and HCC patients show potential usefulness as diagnostic tools. This article is protected by copyright. All rights reserved. PMID: 28555885 [PubMed - as supplied by publisher]

Related Articles Bioinformatics can boost metabolomics research. J Biotechnol. 2017 May 26;: Authors: Meier R, Ruttkies C, Treutler H, Neumann S Abstract Metabolomics is the modern term for the field of small molecule research in biology and biochemistry. Currently, metabolomics is undergoing a transition where the classic analytical chemistry is combined with modern cheminformatics and bioinformatics methods, paving the way for large-scale data analysis. We give some background on past developments, highlight current state-of-the-art approaches, and give a perspective on future requirements. PMID: 28554829 [PubMed - as supplied by publisher]

Related Articles Integrated omics approaches to characterize a nuclear receptor corepressor-associated histone deacetylase in mouse skeletal muscle. Mol Cell Endocrinol. 2017 May 26;: Authors: Gong Y, Cao R, Ding G, Hong S, Zhou W, Lu W, Damle M, Fang B, Wang CC, Qian J, Lie N, Lanzillotta C, Rabinowitz JD, Sun Z Abstract Nuclear receptors regulate gene expression by differential binding to coactivators or corepressors in a ligand-dependent manner, which further recruits a set of epigenome-modifying enzymes that remodel chromatin conformation. Histone acetylation is a major epigenomic change controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC3 is the only HDAC that confers the enzymatic activity to the complexes nucleated by nuclear receptor corepressors NCoR and SMRT. To address the metabolic function of HDAC3, we have deleted it specifically in mouse skeletal muscles. We have performed the following omics profiling in skeletal muscles of these mice: (1) RNA-seq profiling of total RNA; (2) Global nuclear run-on (GRO-seq) analysis of nascent RNAs; (3) Chromatin immuno-precipitation (ChIP-seq) of HDAC3 at both early evening and early morning; (4) proteomics profiling with mass spectrometry; (5) snap-shot metabolomics profiling of water-soluble metabolites at the basal condition; (6) snap-shot metabolomics profiling of lipid species at the basal condition; (7) kinetic fluxomics analysis of glucose utilization using (13)C6-glucose in vivo during treadmill running exercise. These approaches have provided several novel insights into how nuclear receptors regulate circadian rhythm of skeletal muscle fuel metabolism, which has been published elsewhere. Here we present the original datasets and technical details during the execution, analysis, and interpretation of these omics studies. PMID: 28554803 [PubMed - as supplied by publisher]

Related Articles Human blood cell levels of 5-hydroxymethylcytosine (5hmC) decline with age, partly related to acquired mutations in TET2. Exp Hematol. 2016 Nov;44(11):1072-1084 Authors: Buscarlet M, Tessier A, Provost S, Mollica L, Busque L Abstract Epigenetic alteration may play a role in age-associated dysfunction of stem cells and predispose to the development of hematological cancers. We analyzed global levels of hematopoietic 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in a cross-sectional study comprising 198 unrelated individuals from four age categories (neonates, 25-30, 70-75, and >90 years old) by liquid chromatography-electrospray ionization-tandem mass spectrometry with multiple reaction monitoring. X-chromosome inactivation (XCI) ratios and telomere length (TL) were measured in all individuals by polymerase chain reaction. Sequencing of epigenetic regulator genes (including TET2, DNMT3A, ASXL1, IDH1, IDH2, and WT1) was performed in the two older subcohorts. We found that global 5hmC levels declined with age in human blood cells (27.5% reduction from birth to old age, p < 0.0005). The levels of 5mC underwent a more modest reduction (2.4% drop) between newborns and the elderly (p < 0.0005). Low 5hmC was associated with increased skewing of XCI (age-adjusted p = 0.0304) and reduced TL (age-adjusted p = 0.0354), both surrogate markers of clonal dominance. Of the 100 individuals over the age of 70, 16 had somatic mutations in TET2, 14 in DNMT3A, and none in IDH1, IDH2, or WT1. Individuals with TET2 mutations had significantly lower 5hmC (relative to unmutated individuals), whereas DNMT3A-mutated subjects did not. However, mutations in TET2 cannot account solely for the decline in 5hmC levels observed with aging because unmutated older individuals also had lower 5hmC levels compared with younger individuals. This suggests that the age-associated decline in 5hmC is multifactorial. Larger prospective studies are needed to determine whether 5hmC reduction is a biomarker of hematological cancer development. PMID: 27475703 [PubMed - indexed for MEDLINE]

Related Articles Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise. Am J Physiol Cell Physiol. 2016 Jun 01;310(11):C874-84 Authors: Moberg M, Apró W, Ekblom B, van Hall G, Holmberg HC, Blomstrand E Abstract Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo, leucine, BCAA, or EAA (including the BCAA) in random order. Muscle biopsies were taken at rest, immediately after exercise, and following 90 and 180 min of recovery. Following 90 min of recovery the activity of S6 kinase 1 (S6K1) was greater than at rest in all four trials (Placebo<Leucine<BCAA<EAA; P < 0.05 time × supplement), with a ninefold increase in the EAA trial. At this same time point, phosphorylation of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) at Thr(37/46) was unaffected by supplementation, while that of Thr(46) alone exhibited a pattern similar to that of S6K1, being 18% higher with EAA than BCAA. However, after 180 min of recovery this difference between EAA and BCAA had disappeared, although with both these supplements the increases were still higher than with leucine (40%, P < 0.05) and placebo (100%, P < 0.05). In summary, EAA ingestion appears to stimulate translation initiation more effectively than the other supplements, although the results also suggest that this effect is primarily attributable to the BCAA. PMID: 27053525 [PubMed - indexed for MEDLINE]

Related Articles Biochemical Mechanisms and Catabolic Enzymes Involved in Bacterial Estrogen Degradation Pathways. Cell Chem Biol. 2017 May 18;: Authors: Chen YL, Yu CP, Lee TH, Goh KS, Chu KH, Wang PH, Ismail W, Shih CJ, Chiang YR Abstract Estrogens have been classified as group 1 carcinogens by the World Health Organization and represent a significant concern given that they are found in surface waters worldwide, and long-term exposure to estrogen-contaminated water can disrupt sexual development in animals. To date, the estrogen catabolic enzymes and genes remain unknown. Using a tiered functional genomics approach, we identified three estrogen catabolic gene clusters in Sphingomonas sp. strain KC8. We identified several estrone-derived compounds, including 4-hydroxyestrone, a meta-cleavage product, and pyridinestrone acid. The yeast-based estrogen assay suggested that pyridinestrone acid exhibits negligible estrogenic activity. We characterized 17β-estradiol dehydrogenase and 4-hydroxyestrone 4,5-dioxygenase, responsible for the 17-dehydrogenation and meta-cleavage of the estrogen A ring, respectively. The characteristic pyridinestrone acid was detected in estrone-spiked samples collected from two wastewater treatment plants and two suburban rivers in Taiwan. The results significantly expand our understanding of microbial degradation of aromatic steroids at molecular level. PMID: 28552583 [PubMed - as supplied by publisher]

Related Articles Beyond the paradigm: Combining mass spectrometry and nuclear magnetic resonance for metabolomics. Prog Nucl Magn Reson Spectrosc. 2017 May;100:1-16 Authors: Marshall DD, Powers R Abstract Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of biomarkers for human diseases. Nuclear magnetic resonance (NMR) and mass spectrometry (MS) are the analytical tools that are routinely, but separately, used to obtain metabolomics data sets due to their versatility, accessibility, and unique strengths. NMR requires minimal sample handling without the need for chromatography, is easily quantitative, and provides multiple means of metabolite identification, but is limited to detecting the most abundant metabolites (⩾1μM). Conversely, mass spectrometry has the ability to measure metabolites at very low concentrations (femtomolar to attomolar) and has a higher resolution (∼10(3)-10(4)) and dynamic range (∼10(3)-10(4)), but quantitation is a challenge and sample complexity may limit metabolite detection because of ion suppression. Consequently, liquid chromatography (LC) or gas chromatography (GC) is commonly employed in conjunction with MS, but this may lead to other sources of error. As a result, NMR and mass spectrometry are highly complementary, and combining the two techniques is likely to improve the overall quality of a study and enhance the coverage of the metabolome. While the majority of metabolomic studies use a single analytical source, there is a growing appreciation of the inherent value of combining NMR and MS for metabolomics. An overview of the current state of utilizing both NMR and MS for metabolomics will be presented. PMID: 28552170 [PubMed - in process]

Related Articles Mitochondrial Dysfunction in the Diabetic Kidney. Adv Exp Med Biol. 2017;982:553-562 Authors: Sharma K Abstract The role of mitochondria in diabetic complications has been viewed as a source of excess superoxide production leading to cell dysfunction. However, with the lack of benefit of non-specific anti-oxidant approaches this view needs to be re-evaluated. With recent studies using real-time imaging of superoxide, metabolomics, flux studies, transcriptomics and proteomics a new appreciation for the role of mitochondria in the evolution of diabetic kidney disease has emerged. Ongoing studies to further unravel the time course and mechanisms that reduce mitochondrial function will be relevant to novel therapies that could have a major impact on diabetic kidney disease and other diabetic complications. PMID: 28551806 [PubMed - in process]

Related Articles Metabolomic and physico-chemical approach unravel dynamic regulation of calcium in sweet cherry fruit physiology. Plant Physiol Biochem. 2017 May 17;116:68-79 Authors: Michailidis M, Karagiannis E, Tanou G, Karamanoli K, Lazaridou A, Matsi T, Molassiotis A Abstract Calcium (Ca(2)) nutrition has a significant role in fruit physiology; however, the underlying mechanism is still unclear. In this study, fruit quality in response to CaCl2, applied via foliar sprays (Ca(2)) or/and hydro-cooling water (CaHC), was characterized in 'Lapins' cherries at harvest, just after cold storage (20 days at 0 °C) as well as after cold storage followed by 2 days at 20 °C, herein defined as shelf-life period. Data indicated that pre- and post-harvest Ca(2+) applications increased total Ca(2+) and cell wall bound Ca(2+), respectively. Treatment with Ca reduced cracking whereas Ca + CaHC condition depressed stem browning. Both skin penetration and stem removal were affected by Ca(2+) feeding. Also, several color- and antioxidant-related parameters were induced by Ca(2+) treatments. Metabolomic analysis revealed significant alterations in primary metabolites among the Ca(2+) treatments, including sugars (eg., glucose, fructose), soluble alcohols (eg., arabitol, sorbitol), organic acids (eg.,malate, quinate) and amino acids (eg., glycine, beta-alanine). This work helps to improve our knowledge on the fruit's response to Ca(2+) nutrition. PMID: 28551418 [PubMed - as supplied by publisher]

Related Articles Process specific differential metabolomes for industrial gochujang types (pepper paste) manufactured using white rice, brown rice, and wheat. Food Chem. 2017 Nov 01;234:416-424 Authors: Jang YK, Shin GR, Jung ES, Lee S, Lee S, Singh D, Jang ES, Shin DJ, Kim HJ, Shin HW, Moon BS, Lee CH Abstract The metabolic perplexes for gochujang (GCJ) fermentative bioprocess, a traditional Korean pepper paste, has largely remain equivocal for preparative conditions and raw material (RM) additives exacerbating its commercial standardization. Herein, we outlined a differential non-targeted metabolite profiling for three GCJ (white rice-WR; brown rice-BR; wheat-WT) under varying processing steps (P1 - fermentation; P2 - meju addition; P3 - ripening; and P4 - red pepper addition). We correlated the process specific metabolomes with corresponding physicochemical factors, enzymatic phenotypes, and bioactivities for GCJ-types. The P1 was characterized by a uniform increase in the levels of RM-derived lysoPCs. In contrast, P2 was observed with proportionally higher levels of meju-released isoflavones and soyasaponins in WR-GCJ, followed by BR and WT-GCJ. The P3 involved a cumulative increase in primary metabolites in all GCJ samples except lower organic acid contents in WT-GCJ. The pepper derived flavonoids and alkaloids were selectively increased while P4 in all GCJ-types. PMID: 28551255 [PubMed - in process]

Related Articles 'Omic' Approaches to Study Uropathogenic Escherichia coli Virulence. Trends Microbiol. 2017 May 24;: Authors: Lo AW, Moriel DG, Phan MD, Schulz BL, Kidd TJ, Beatson SA, Schembri MA Abstract Uropathogenic Escherichia coli (UPEC) is a pathogen of major significance to global human health and is strongly associated with rapidly increasing antibiotic resistance. UPEC is the primary cause of urinary tract infection (UTI), a disease that involves a complicated pathogenic pathway of extracellular and intracellular lifestyles during interaction with the host. The application of multiple 'omic' technologies, including genomics, transcriptomics, proteomics, and metabolomics, has provided enormous knowledge to our understanding of UPEC biology. Here we outline this progress and present a view for future developments using these exciting forefront technologies to fully comprehend UPEC pathogenesis in the context of infection. PMID: 28550944 [PubMed - as supplied by publisher]

Related Articles Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating. Br J Cancer. 2016 Sep 06;115(6):635-40 Authors: Michalopoulou E, Bulusu V, Kamphorst JJ Abstract Cancer is fundamentally a disease of uncontrolled cell proliferation. Tumour metabolism has emerged as an exciting new discipline studying how cancer cells obtain the necessary energy and cellular 'building blocks' to sustain growth. Glucose and glutamine have long been regarded as the key nutrients fuelling tumour growth. However, the inhospitable tumour microenvironment of certain cancers, like pancreatic cancer, causes the supply of these nutrients to be chronically insufficient for the demands of proliferating cancer cells. Recent work has shown that cancer cells are able to overcome this nutrient insufficiency by scavenging alternative substrates, particularly proteins and lipids. Here, we review recent work identifying the endocytic process of macropinocytosis and subsequent lysosomal processing as an important substrate-acquisition route. In addition, we discuss the impact of hypoxia on fatty acid metabolism and the relevance of exogenous lipids for supporting tumour growth as well as the routes by which tumour cells can access these lipids. Together, these cancer-specific scavenging pathways provide a promising opportunity for therapeutic intervention. PMID: 27537393 [PubMed - indexed for MEDLINE]

Related Articles Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis. J Am Soc Nephrol. 2016 Dec;27(12):3780-3787 Authors: Kurella Tamura M, Chertow GM, Depner TA, Nissenson AR, Schiller B, Mehta RL, Liu S, Sirich TL, FHN Study Abstract Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis. PMID: 27444566 [PubMed - indexed for MEDLINE]

Related Articles Early changes in the metabolic profile of activated CD8(+) T cells. BMC Cell Biol. 2016 Jul 07;17(1):28 Authors: Cammann C, Rath A, Reichl U, Lingel H, Brunner-Weinzierl M, Simeoni L, Schraven B, Lindquist JA Abstract BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes. RESULTS: We found that proliferation inducing conditions result in an increase in key glycolytic metabolites, whereas the citric acid cycle remains unaffected. The upregulation of glycolysis led to a strong lactate production, which depends upon AKT/PKB, but not mTOR. The observed upregulation of lactate dehydrogenase results in increased lactate production, which we found to be dependent on IL-2 and to be required for proliferation. Additionally we observed upregulation of Glucose-transporter 1 (GLUT1) and glucose uptake upon stimulation, which were surprisingly not influenced by AKT inhibition. CONCLUSIONS: Our findings suggest that AKT plays a central role in upregulating glycolysis via induction of lactate dehydrogenase expression, but has no impact on glucose uptake of T cells. Furthermore, under apoptosis inducing conditions, T cells are not able to upregulate glycolysis and induce lactate production. In addition maintaining high glycolytic rates strongly depends on IL-2 production. PMID: 27387758 [PubMed - indexed for MEDLINE]

Related Articles Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017 May 25;7(5):e014932 Authors: Xu H, Wang H, Guan J, Yi H, Qian Y, Zou J, Xia Y, Fu Y, Li X, Jiao X, Huang H, Dong P, Yu Z, Yang J, Xiang M, Li J, Chen Y, Wang P, Sun Y, Li Y, Zheng X, Jia W, Yin S Abstract OBJECTIVES: Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. METHODS/DESIGN: This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. TRIAL REGISTRATION NUMBER: NCT02886156; pre-results. PMID: 28550021 [PubMed - in process]

Related Articles Potential metabolomic biomarkers for reliable diagnosis of Behcet's disease using gas chromatography with time-of-flight mass spectrometry. Joint Bone Spine. 2017 May 23;: Authors: Ahn JK, Kim J, Hwang J, Song J, Kim KH, Cha HS Abstract OBJECTIVES: Although many diagnostic criteria of Behcet's disease (BD) have been developed and revised by experts, diagnosing BD is still complicated and challenging. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. The purposes of this study were to investigate distinctive metabolic changes in serum samples of BD patients and to identify metabolic candidate biomarkers for reliable diagnosis of BD using the metabolomics platform. METHODS: Metabolomic profiling of 90 serum samples from 45 BD patients and 45 healthy controls (HCs) was performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses. RESULTS: A total of 104 metabolites were identified from samples. The serum metabolite profiles obtained from GC/TOF-MS analysis can distinguish BD patients from HC group in discovery set. The variation values of the partial least squared-discrimination analysis (PLS-DA) model are R(2)X of 0.246, R(2)Y of 0.913, and Q(2) of 0.852, respectively, indicating strong explanation and prediction capabilities of the model. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid, and oleic acid were selected and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.998) in the discovery set and independent set. The principal component analysis showed clear discrimination of BD and HC groups by the five metabolic biomarkers in independent set. CONCLUSIONS: This is the first report on characteristic metabolic profiles and potential metabolite biomarkers in serum for reliable diagnosis of BD using GC/TOF-MS. PMID: 28549946 [PubMed - as supplied by publisher]