PubMed

Related Articles Metabolomic Analysis of Schizosaccharomyces pombe: Sample Preparation, Detection, and Data Interpretation. Cold Spring Harb Protoc. 2016 Dec 01;2016(12):pdb.top079921 Authors: Pluskal T, Yanagida M Abstract Metabolomics is a modern field of chemical biology that strives to simultaneously quantify hundreds of cellular metabolites. Techniques for metabolomic analysis in Schizosaccharomyces pombe have only recently been developed. Here we introduce methods that provide a complete workflow for metabolomic analysis in S. pombe Based on available literature, we estimate the yeast metabolome to comprise on the order of several thousand different metabolites. We discuss the feasibility of extraction and detection of such a large number of metabolites, and the influences of various parameters on the results. Among the parameters addressed are cell cultivation conditions, metabolite extraction techniques, and detection and quantification methods. Further, we provide recommendations on data management and data processing for metabolomic experiments, and describe possible pitfalls regarding the interpretation of metabolomic data. Finally, we briefly discuss potential future developments of this technique. PMID: 27934694 [PubMed - in process]

Related Articles PlantMAT: A Metabolomics Tool for Predicting the Specialized Metabolic Potential of a System and for Large-Scale Metabolite Identifications. Anal Chem. 2016 Dec 06;88(23):11373-11383 Authors: Qiu F, Fine DD, Wherritt DJ, Lei Z, Sumner LW Abstract Custom software entitled Plant Metabolite Annotation Toolbox (PlantMAT) has been developed to address the number one grand challenge in metabolomics, which is the large-scale and confident identification of metabolites. PlantMAT uses informed phytochemical knowledge for the prediction of plant natural products such as saponins and glycosylated flavonoids through combinatorial enumeration of aglycone, glycosyl, and acyl subunits. Many of the predicted structures have yet to be characterized and are absent from traditional chemical databases, but have a higher probability of being present in planta. PlantMAT allows users to operate an automated and streamlined workflow for metabolite annotation from a user-friendly interface within Microsoft Excel, a familiar, easily accessed program for chemists and biologists. The usefulness of PlantMAT is exemplified using ultrahigh-performance liquid chromatography-electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-QTOF-MS/MS) metabolite profiling data of saponins and glycosylated flavonoids from the model legume Medicago truncatula. The results demonstrate PlantMAT substantially increases the chemical/metabolic space of traditional chemical databases. Ten of the PlantMAT-predicted identifications were validated and confirmed through the isolation of the compounds using ultrahigh-performance liquid chromatography-mass spectrometry-solid-phase extraction (UHPLC-MS-SPE) followed by de novo structural elucidation using 1D/2D nuclear magnetic resonance (NMR). It is further demonstrated that PlantMAT enables the dereplication of previously identified metabolites and is also a powerful tool for the discovery of structurally novel metabolites. PMID: 27934098 [PubMed - in process]

Related Articles Serum Metabolomics Analysis of Quercetin against Acrylamide-Induced Toxicity in Rats. J Agric Food Chem. 2016 Dec 07;64(48):9237-9245 Authors: Yang S, Cao C, Chen S, Hu L, Bao W, Shi H, Zhao X, Sun C Abstract The current study aimed to investigate whether quercetin plays a protective role in acrylamide (AA)-induced toxicity using a metabolomics approach. Rats were randomly divided into groups as follows: control, treated with AA [5 mg/kg body weight (bw)], treated with different dosages of quercetin (10 and 50 mg/kg bw, respectively), and treated with two dosages of quercetin plus AA. After a 16 week treatment, rat serum was collected for metabolomics analysis. Biochemical tests and examination of liver histopathology were further conducted to verify metabolic alterations. Twelve metabolites were identified for which intensities were significantly changed (increased or reduced) as a result of the treatment. These metabolites included isorhamnetin, citric acid, pantothenic acid, isobutyryl-l-carnitine, eicosapentaenoic acid, docosahexaenoic acid, sphingosine 1-phosphate, lysoPC(20:4), lysoPC(22:6), lysoPE(20:3), undecanedioic acid, and dodecanedioic acid. The results indicate that quercetin (50 mg/kg bw) exerts partial protective effects on AA-induced toxicity by reducing oxidative stress, protecting the mitochondria, and regulating lipid metabolism. PMID: 27933994 [PubMed - in process]

Related Articles Food Fingerprinting: Metabolomic Approaches for Geographical Origin Discrimination of Hazelnuts (Corylus avellana) by UPLC-QTOF-MS. J Agric Food Chem. 2016 Dec 07;64(48):9253-9262 Authors: Klockmann S, Reiner E, Bachmann R, Hackl T, Fischer M Abstract Ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for geographical origin discrimination of hazelnuts (Corylus avellana L.). Four different LC-MS methods for polar and nonpolar metabolites were evaluated with regard to best discrimination abilities. The most suitable method was used for analysis of 196 authentic samples from harvest years 2014 and 2015 (Germany, France, Italy, Turkey, Georgia), selecting and identifying 20 key metabolites with significant differences in abundancy (5 phosphatidylcholines, 3 phosphatidylethanolamines, 4 diacylglycerols, 7 triacylglycerols, and γ-tocopherol). Classification models using soft independent modeling of class analogy (SIMCA), linear discriminant analysis based on principal component analysis (PCA-LDA), support vector machine classification (SVM), and a customized statistical model based on confidence intervals of selected metabolite levels were created, yielding 99.5% training accuracy at its best by combining SVM and SIMCA. Forty nonauthentic hazelnut samples were subsequently used to estimate as realistically as possible the prediction capacity of the models. PMID: 27933993 [PubMed - in process]

Related Articles Metabolic Effects of Cobalt Ferrite Nanoparticles on Cervical Carcinoma Cells and Nontumorigenic Keratinocytes. J Proteome Res. 2016 Dec 02;15(12):4337-4348 Authors: Oliveira AB, de Moraes FR, Candido NM, Sampaio I, Paula AS, de Vasconcellos A, Silva TC, Miller AH, Rahal P, Nery JG, Calmon MF Abstract The cytotoxic response, cellular uptake, and metabolomic profile of HeLa and HaCaT cell lines treated with cobalt ferrite nanoparticles (CoFe2O4 NPs) were investigated in this study. Cell viability assays showed low cytotoxicity caused by the uptake of the nanoparticles at 2 mg/mL. However, metabolomics revealed that these nanoparticles impacted cell metabolism even when tested at a concentration that presented low cytotoxicity according to the cell viability assay. The two cell lines shared stress-related metabolic changes such as increase in alanine and creatine levels. A reduced level of fumarate was also observed in HeLa cells after treatment with the nanoparticles, and this alteration can inhibit tumorigenesis. Fumarate is considered to be an oncometabolite that can inhibit prolyl hydroxylase, and this inhibition stabilizes HIF1α, one of the master regulators of tumorigenesis that promotes tumor growth and development. In summary, this study showed that nanoparticle-treated HeLa cells demonstrated decreased concentrations of metabolites associated with cell proliferation and tumor growth. The results clearly indicated that treatment with these nanoparticles might cause a perturbation in cellular metabolism. PMID: 27933982 [PubMed - in process]

Related Articles GeneNetwork: A Toolbox for Systems Genetics. Methods Mol Biol. 2017;1488:75-120 Authors: Mulligan MK, Mozhui K, Prins P, Williams RW Abstract The goal of systems genetics is to understand the impact of genetic variation across all levels of biological organization, from mRNAs, proteins, and metabolites, to higher-order physiological and behavioral traits. This approach requires the accumulation and integration of many types of data, and also requires the use of many types of statistical tools to extract relevant patterns of covariation and causal relations as a function of genetics, environment, stage, and treatment. In this protocol we explain how to use the GeneNetwork web service, a powerful and free online resource for systems genetics. We provide workflows and methods to navigate massive multiscalar data sets and we explain how to use an extensive systems genetics toolkit for analysis and synthesis. Finally, we provide two detailed case studies that take advantage of human and mouse cohorts to evaluate linkage between gene variants, addiction, and aging. PMID: 27933521 [PubMed - in process]

Related Articles Non-targeted Plasma Metabolome of Early and Late Lactation Gilts. Front Mol Biosci. 2016;3:77 Authors: Rempel LA, Miles JR, Oliver WT, Broeckling CD Abstract Female pigs nursing their first litter (first-parity gilts) have increased energy requirements not only to support their piglets, but they themselves are still maturing. Non-targeted plasma metabolomics were used to investigate the differences between (1) post-farrowing and weaning (early or late lactation), (2) degree of body condition loss after lactation (extreme or minimal), and (3) interactions; to potentially identify compounds or pathways that could aide in alleviating energetic demands of lactation in gilts. Twenty first-parity gilts were selected with similar (P ≥ 0.4475) number of piglets born and nursed, and similar (P ≥ 0.3141) body condition traits (e.g., body weight and backfat thickness) post-farrowing, yet exhibited minimal or extreme loss (P ≤ 0.0094) in body weight (8.6 ± 1.48 kg and 26.1 ± 1.90 kg, respectively) and backfat thickness (1.3 ± 0.67 mm and 4.7 ± 0.86 mm, respectively) following lactation (weaning). Plasma samples from first-parity gilts at post-farrowing and weaning were investigated using UPLC-MS and GC-MS to generate a comprehensive metabolic profile. Each approach yielded approximately 700 detected features. An ANOVA was performed on each detected compound in R for time of collection, body condition change, and the interaction, followed by a false discovery correction. Two unknown features were different (P ≤ 0.05) for extreme vs. minimal body condition change. Several compound differences (P ≤ 0.05) were identified between post-farrowing and weaning. Thirty-two features detected by UPLC-MS had at least a log2 fold-change of ±1.0 while only 18 features had a log2 fold-change of ±0.6 or more for the significant GC-MS features. Annotation implicated various metabolic pathways. Creatinine was greater at weaning (P = 0.0224) and others have reported increased serum concentrations of creatinine in response to body weight loss. Hippurate and caprolactam, associated with protein catabolism, were also greater (P ≤ 0.0166) at weaning. Phospholipid features (P ≤ 0.0347) and inositol-related features (P ≤ 0.0236) were also greater at weaning. Inositol features may exert insulin-like effects. The energetic demands of lactation in gilts nursing their first litter indicated a greater difference exists between early and late lactation regardless of body condition loss. PMID: 27933298 [PubMed - in process]

Related Articles Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men. Front Med (Lausanne). 2016;3:57 Authors: Kujala UM, Peltonen M, Laine MK, Kaprio J, Heinonen OJ, Sundvall J, Eriksson JG, Jula A, Sarna S, Kainulainen H Abstract AIMS/HYPOTHESIS: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. METHODS: Older Finnish men enriched with individuals having been athletes in young adulthood (n = 593; mean age 72.6 ± 5.9 years) responded to questionnaires, participated in a clinical examination including assessment of body composition with bioimpedance and gave fasting blood samples for various analytes as well as participated in a 2-h 75 g oral glucose tolerance test. Metabolomics measurements from serum included BCAAs (isoleucine, leucine, and valine). RESULTS: Out of the 593 participants, 59 had previously known type 2 diabetes, further 67 had screen-detected type 2 diabetes, 127 impaired glucose tolerance, and 125 impaired fasting glucose, while 214 had normal glucose regulation and one had missing glucose tolerance information. There were group differences in all of the BCAA concentrations (p ≤ 0.005 for all BCAAs), such that those with normal glucose tolerance had the lowest and those with diabetes mellitus had the highest BCAA concentrations. All BCAA levels correlated positively with body fat percentage (r = 0.29-0.34, p < 0.0001 for all). Expected associations with high BCAA concentrations and unfavorable metabolic profile indicators from metabolomics analysis were found. Except for glucose concentrations, the associations were stronger with isoleucine and leucine than with valine. CONCLUSION/INTERPRETATION: The findings provided further support for our hypothesis by strengthening the idea that the efficiency of BCAA catabolism may be mechanistically involved in the regulation of fat oxidation, thus affecting the levels of metabolic disease risk factors. PMID: 27933294 [PubMed - in process]

Related Articles Type 1 reaction in leprosy patients corresponds with a decrease in pro-resolving and an increase in pro-inflammatory lipid mediators. J Infect Dis. 2016 Dec 08;: Authors: Silva CA, Webb K, Andre BG, Marques MA, de Carvalho FM, de Macedo CS, Pinheiro RO, Sarno EN, Pessolani MC, Belisle JT Abstract BACKGROUND: Type 1 reaction (T1R) is an acute Th1 inflammatory episode in leprosy patients. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention. METHODS: Metabolomics-based analyses of sera from T1R (n=7) and T1R-free (n=9) patients were conducted via liquid chromatography-mass spectrometry (LC-MS). Serum metabolites that significantly differed (p<0.05) with a log2 fold change of ≥1.0 between patient groups were interrogated against known metabolic pathways. The structural identification of targeted metabolites were confirmed and abundance changes validated by mass spectrometry and enzyme-linked immunoassay (EIA). RESULTS: Forty metabolic pathways were perturbed in T1R patients, with 71 dysregulated metabolites mapping to pathways for lipid mediators of inflammation. Of note was an increase in the abundance of the pro-inflammatory leukotriene B4 (LTB4), and a corresponding decrease in pro-resolving resolvin D1 (RvD1). Also, levels of prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) in T1R patients were significantly increased, while prostaglandin E2 (PGE2) was decreased. CONCLUSIONS: The dysregulation of metabolic pathways leading to abundance shifts between pro-inflammatory and pro-resolving lipid mediators provides a link between metabolic and cellular immune responses that result in the Th1-mediated pathology of T1R. PMID: 27932613 [PubMed - as supplied by publisher]

Related Articles Predictive diagnosis of major depression using NMR-based metabolomics and least-squares support vector machine. Clin Chim Acta. 2016 Dec 05;: Authors: Zheng H, Zheng P, Zhao L, Jia J, Tang S, Xu P, Xie P, Gao H Abstract BACKGROUND: Major depressive (MD) disorder is a serious psychiatric disorder that can result in suicidal behavior if not treated. The MD diagnosis using a standardized instrument instead of a structured interview will be advantageous for treatment and management of the MD, but so far no such technique exists. We developed an integrated analytical method of NMR-based metabolomics and least squares-support vector machine (LS-SVM) for predictive diagnosis of the MD. METHODS: The metabolite profiles in clinical plasma samples obtained from 72 depressive patients and 54 healthy subjects were analyzed by NMR spectroscopy. Then, LS-SVM models with different kernels were trained and tested using 80% and 20% of samples, respectively. RESULTS: We found that the best performance for the MD prediction was achieved by LS-SVM equipped with RBF kernel. Moreover, the predictive performance of the MD using multi-biomarkers was largely improved as compared with that using a single biomarker. In this study, the LS-SVM-RBF using glucose-lipid signaling can achieve the MD prediction with the AUC values of 0.94 (0.89-0.99) in the training set and 0.96 (0.92-1.00) in the test set. CONCLUSION: The LS-SVM-RBF using glucose-lipid signaling obtained from NMR spectroscopy can be used as an auxiliary diagnostic tool for the MD. PMID: 27931880 [PubMed - as supplied by publisher]

Related Articles Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness. Toxicology. 2016 Nov 30;372:22-33 Authors: Abdullah L, Evans JE, Joshi U, Crynen G, Reed J, Mouzon B, Baumann S, Montague H, Zakirova Z, Emmerich T, Bachmeier C, Klimas N, Sullivan K, Mullan M, Ait-Ghezala G, Crawford F Abstract Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI. PMID: 27931520 [PubMed - in process]

Expanding the Klebsiella pneumoniae volatile metabolome using advanced analytical instrumentation for the detection of novel metabolites. J Appl Microbiol. 2016 Dec 08;: Authors: Rees CA, Franchina FA, Nordick KV, Kim PJ, Hill JE Abstract AIMS: The purpose of this study was to identify the volatile molecules produced by the pathogenic Gram-negative bacterium Klebsiella pneumoniae (ATCC 13883) during in vitro growth using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). METHODS AND RESULTS: K. pneumoniae ATCC 13883 was incubated in lysogeny broth (LB) to mid-exponential and stationary growth phases. Headspace volatile molecules from culture supernatants were concentrated using solid-phase microextraction (SPME) and analyzed via GC×GC-TOFMS. Ninety-two K. pneumoniae-associated volatile molecules were detected, of which 78 (85%) were detected at both phases of growth and 14 (15%) were detected at either mid-exponential or stationary growth phases. CONCLUSIONS: This study has increased the total number of reported K. pneumoniae-associated volatile molecules from 77 to 150, demonstrating the sensitivity and resolution achieved by employing GC×GC-TOFMS for the analysis of bacterial headspace volatiles. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents an early-stage comprehensive volatile metabolomic analysis of an opportunistic bacterial pathogen. Characterizing the volatile molecules produced by K. pneumoniae during in vitro growth could provide us with a better understanding of this organisms' metabolism; an area that has not been extensively studied to-date. This article is protected by copyright. All rights reserved. PMID: 27930839 [PubMed - as supplied by publisher]

Inflammatory Bowel Disease Meets Systems Biology: A Multi-Omics Challenge and Frontier. OMICS. 2016 Dec;20(12):692-698 Authors: Palmieri O, Mazza T, Castellana S, Panza A, Latiano T, Corritore G, Andriulli A, Latiano A Abstract The inflammatory bowel disease (IBD) is a systemic disease that is characterized by the inflammation of the gastrointestinal tract. It includes ulcerative colitis and the Crohn's disease. Presently, IBD is one of the most investigated common complex human disorders, although its causes remain unclear. Multi-omics mechanisms involving genomic, transcriptomic, proteomic, and epigenomic variations, not to forget the miRNome, together with environmental contributions, result in an impairment of the immune system in persons with IBD. Such interactions at multiple levels of biology and in concert with the environment constitute the actual engine of this complex disease, demanding a multifactorial and multi-omics perspective to better understand the root causes of IBD. This expert analysis reviews and examines the latest literature and underscores, from the perspective of systems biology, the value of multi-omics technologies as opportunities to unravel the "IBD integrome." We anticipate that multi-omics research will accelerate the new discoveries and insights on IBD in the near future. It shall also pave the way for early diagnosis and help clinicians and families with IBD to forecast and make informed decisions about the prognosis and, possibly, personalized therapeutics in the future. PMID: 27930092 [PubMed - in process]

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies. Int J Mol Sci. 2016 Dec 05;17(12): Authors: Jobard E, Trédan O, Postoly D, André F, Martin AL, Elena-Herrmann B, Boyault S Abstract The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies. PMID: 27929400 [PubMed - in process]

Metabolism of HT-2 Toxin and T-2 Toxin in Oats. Toxins (Basel). 2016 Dec 05;8(12): Authors: Meng-Reiterer J, Bueschl C, Rechthaler J, Berthiller F, Lemmens M, Schuhmacher R Abstract The Fusarium mycotoxins HT-2 toxin (HT2) and T-2 toxin (T2) are frequent contaminants in oats. These toxins, but also their plant metabolites, may contribute to toxicological effects. This work describes the use of (13)C-assisted liquid chromatography-high-resolution mass spectrometry for the first comprehensive study on the biotransformation of HT2 and T2 in oats. Using this approach, 16 HT2 and 17 T2 metabolites were annotated including novel glycosylated and hydroxylated forms of the toxins, hydrolysis products, and conjugates with acetic acid, putative malic acid, malonic acid, and ferulic acid. Further targeted quantitative analysis was performed to study toxin metabolism over time, as well as toxin and conjugate mobility within non-treated plant tissues. As a result, HT2-3-O-β-d-glucoside was identified as the major detoxification product of both parent toxins, which was rapidly formed (to an extent of 74% in HT2-treated and 48% in T2-treated oats within one day after treatment) and further metabolised. Mobility of the parent toxins appeared to be negligible, while HT2-3-O-β-d-glucoside was partly transported (up to approximately 4%) through panicle side branches and stem. Our findings demonstrate that the presented combination of untargeted and targeted analysis is well suited for the comprehensive elucidation of mycotoxin metabolism in plants. PMID: 27929394 [PubMed - in process]

Related Articles Metabolic Profiling Reveals Differences in Plasma Concentrations of Arabinose and Xylose after Consumption of Fiber-Rich Pasta and Wheat Bread with Differential Rates of Systemic Appearance of Exogenous Glucose in Healthy Men. J Nutr. 2016 Dec 07;: Authors: Pantophlet AJ, Wopereis S, Eelderink C, Vonk RJ, Stroeve JH, Bijlsma S, van Stee L, Bobeldijk I, Priebe MG Abstract BACKGROUND: The consumption of products rich in cereal fiber and with a low glycemic index is implicated in a lower risk of metabolic diseases. Previously, we showed that the consumption of fiber-rich pasta compared with bread resulted in a lower rate of appearance of exogenous glucose and a lower glucose clearance rate quantified with a dual-isotope technique, which was in accordance with a lower insulin and glucose-dependent insulinotropic polypeptide response. OBJECTIVE: To gain more insight into the acute metabolic consequences of the consumption of products resulting in differential glucose kinetics, postprandial metabolic profiles were determined. METHODS: In a crossover study, 9 healthy men [mean ± SEM age: 21 ± 0.5 y; mean ± SEM body mass index (kg/m(2)): 22 ± 0.5] consumed wheat bread (132 g) and fresh pasta (119 g uncooked) enriched with wheat bran (10%) meals. A total of 134 different metabolites in postprandial plasma samples (at -5, 30, 60, 90, 120, and 180 min) were quantified by using a gas chromatography-mass spectrometry-based metabolomics approach (secondary outcomes). Two-factor ANOVA and advanced multivariate statistical analysis (partial least squares) were applied to detect differences between both food products. RESULTS: Forty-two different postprandial metabolite profiles were identified, primarily representing pathways related to protein and energy metabolism, which were on average 8% and 7% lower after the men consumed pasta rather than bread, whereas concentrations of arabinose and xylose were 58% and 53% higher, respectively. Arabinose and xylose are derived from arabinoxylans, which are important components of wheat bran. The higher bioavailability of arabinose and xylose after pasta intake coincided with a lower rate of appearance of glucose and amino acids. We speculate that this higher bioavailability is due to higher degradation of arabinoxylans by small intestinal microbiota, facilitated by the higher viscosity of arabinoxylans after pasta intake than after bread intake. CONCLUSION: This study suggests that wheat bran, depending on the method of processing, can increase the viscosity of the meal bolus in the small intestine and interfere with macronutrient absorption in healthy men, thereby influencing postprandial glucose and insulin responses. This trial was registered at www.controlled-trials.com as ISRCTN42106325. PMID: 27927976 [PubMed - as supplied by publisher]

Related Articles Tumour biomarkers: homeostasis as a novel prognostic indicator. Open Biol. 2016 Dec;6(12): Authors: Falco M, Palma G, Rea D, De Biase D, Scala S, D'Aiuto M, Facchini G, Perdonà S, Barbieri A, Arra C Abstract The term 'personalized medicine' refers to a medical procedure that consists in the grouping of patients based on their predicted individual response to therapy or risk of disease. In oncologic patients, a 'tailored' therapeutic approach may potentially improve their survival and well-being by not only reducing the tumour, but also enhancing therapeutic response and minimizing the adverse effects. Diagnostic tests are often used to select appropriate and optimal therapies that rely both on patient genome and other molecular/cellular analysis. Several studies have shown that lifestyle and environmental factors can influence the epigenome and that epigenetic events may be involved in carcinogenesis. Thus, in addition to traditional biomarkers, epigenetic factors are raising considerable interest, because they could potentially be used as an excellent tool for cancer diagnosis and prognosis. In this review, we summarize the role of conventional cancer genetic biomarkers and their association with epigenomics. Furthermore, we will focus on the so-called 'homeostatic biomarkers' that result from the physiological response to cancer, emphasizing the concept that an altered 'new' homeostasis influence not only tumour environment, but also the whole organism. PMID: 27927793 [PubMed - in process]

Related Articles Metabolic and functional characterization of effects of developmental temperature in Drosophila melanogaster. Am J Physiol Regul Integr Comp Physiol. 2016 Dec 07;:ajpregu.00268.2016 Authors: Schou MF, Kristensen TN, Pedersen A, Karlsson GB, Loeschcke V, Malmendal A Abstract The ability of ectotherms to respond to changes in their thermal environment through plastic mechanisms is central to their adaptive capability. However, we still lack knowledge on physiological and functional responses by which ectotherms acclimate to temperatures during development, and in particular, how physiological stress at extreme temperatures may counteract beneficial acclimation responses at benign temperatures. We exposed Drosophila melanogaster to ten developmental temperatures covering their entire permissible temperature range. We obtained metabolic profiles and reaction norms for several functional traits: egg-to-adult viability, developmental time, and heat and cold tolerance. Females were more heat tolerant than males, whereas no sexual dimorphism was found in cold tolerance. A group of metabolites, mainly free amino acids, had linear reaction norms. Several energy carrying molecules, as well as some sugars, showed distinct inverted u-shaped norms of reaction across the thermal range, resulting in a positive correlation between metabolite intensities and egg-to-adult viability. At extreme temperatures, low levels of these metabolites were interpreted as a response characteristic of costs of homeostatic perturbations. Our results provide novel insights into a range of metabolites reported to be central for the acclimation response, and suggest several new candidate metabolites. Low and high temperatures result in different adaptive physiological responses, but they also have commonalities likely to be a result of the failure to compensate for the physiological stress. We suggest that the regulation of metabolites that are tightly connected to the performance curve is important for the ability of ectotherms to cope with variation in temperature. PMID: 27927623 [PubMed - as supplied by publisher]

Discovery and identification of potential biomarkers for alcohol-induced oxidative stress based on cellular metabolomics. Biomed Chromatogr. 2016 Dec 07;: Authors: Hu Q, Wei J, Liu Y, Fei X, Hao Y, Pei D, Di D Abstract Biomarkers involved in alcohol-induced oxidative stress play an important role in alcoholic liver disease prevention and diagnosis. Alcohol-induced oxidative stress in human liver L-02 cells was used to discover the potential biomarkers. Metabolites from L-02 cells induced by alcohol were measured by high-performance liquid chromatography and mass spectrometry. Fourteen metabolites that allowed discrimination between control and model groups were discovered by multivariate statistical data analysis (i.e. principal components analysis, orthogonal partial least-squares discriminate analysis). Based on the retention time, UV spectrum and LC-MS findings of the samples and compared with the authentic standards, eight biomarkers involved in alcohol-induced oxidative stress, namely, malic acid, oxidized glutathione, reduced glutathione, adenosine triphosphate, phenylalanine, adenosine monophosphate, nitrotyrosine, and tryptophan, were identified. These biomarkers offered important targets for disease diagnosis and other researches. PMID: 27925248 [PubMed - as supplied by publisher]

Production of Phloroglucinol, a Platform Chemical, in Arabidopsis using a Bacterial Gene. Sci Rep. 2016 Dec 07;6:38483 Authors: Abdel-Ghany SE, Day I, Heuberger AL, Broeckling CD, Reddy AS Abstract Phloroglucinol (1,3,5-trihydroxybenzene; PG) and its derivatives are phenolic compounds that are used for various industrial applications. Current methods to synthesize PG are not sustainable due to the requirement for carbon-based precursors and co-production of toxic byproducts. Here, we describe a more sustainable production of PG using plants expressing a native bacterial or a codon-optimized synthetic PhlD targeted to either the cytosol or chloroplasts. Transgenic lines were analyzed for the production of PG using gas and liquid chromatography coupled to mass spectroscopy. Phloroglucinol was produced in all transgenic lines and the line with the highest PhlD transcript level showed the most accumulation of PG. Over 80% of the produced PG was glycosylated to phlorin. Arabidopsis leaves have the machinery to glycosylate PG to form phlorin, which can be hydrolyzed enzymatically to produce PG. Furthermore, the metabolic profile of plants with PhlD in either the cytosol or chloroplasts was altered. Our results provide evidence that plants can be engineered to produce PG using a bacterial gene. Phytoproduction of PG using a bacterial gene paves the way for further genetic manipulations to enhance the level of PG with implications for the commercial production of this important platform chemical in plants. PMID: 27924918 [PubMed - in process]