PubMed

Investigations on the cell metabolomics basis of multidrug resistance from tumor cells by ultra-performance liquid chromatography-mass spectrometry. Anal Bioanal Chem. 2016 Jul 5; Authors: Zhang R, Zhuang X, Zong L, Liu S, Liu Z, Song F Abstract Although anticancer drug resistance has been linked to high expression of P-glycoprotein and the enhanced DNA repair ability, the biochemical process and the underlying mechanisms of drug resistance are not clear. In order to clarify the biochemical mechanisms of drug resistance during anticancer drug treatment, we studied the metabolomics of MCF-7/S and MCF-7/Adr cell lines, the COC1 and COC1/DDP cell lines, including the metabolic pathways of multidrug-resistant tumor cells and the changes of endogenous substances in cells. The intracellular metabolites were profiled using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, 24 biomarkers in MCF-7/Adr cells and 15 biomarkers in COC1/DDP cells that are involved in some important metabolic pathways were putatively identified. Several metabolic pathways are changed in tumor cells showing drug resistance, such as protein synthesis pathways, cysteine synthesis, the glutamine metabolic pathway, and the ammonia cycle; the first of these are involved in the synthesis of some important proteins including membrane proteins, multidrug resistance-associated proteins, and P-glycoprotein (P-gp). Proteins related to drug resistance were overexpressed in multidrug-resistant tumor cells. These proteins depended on energy and play important roles in the emergence of drug resistance. The changes in glutathione and cysteine metabolic pathways showed that the cells can activate related metabolic pathways and reduce the cell apoptosis when they encounter oxidative damage. These findings indicate that drug resistance is likely associated with increased P-gp synthesis and reduced apoptosis of tumor cells. Graphical Abstract Drug resistance was charactered in the changing of genomics and proteomics. Like enhancing DNA repair, reducing uptake, high P-g protein expression. Here, we studied the changes of metabolite pathway which could be also play an imported role in drug resistance. PMID: 27379392 [PubMed - as supplied by publisher]

Current Advances in the Metabolomics Study on Lotus Seeds. Front Plant Sci. 2016;7:891 Authors: Zhu M, Liu T, Guo M Abstract Lotus (Nelumbo nucifera), which is distributed widely throughout Asia, Australia and North America, is an aquatic perennial that has been cultivated for over 2,000 years. It is very stimulating that almost all parts of lotus have been consumed as vegetable as well as food, especially the seeds. Except for the nutritive values of lotus, there has been increasing interest in its potential as functional food due to its rich secondary metabolites, such as flavonoids and alkaloids. Not only have these metabolites greatly contributed to the biological process of lotus seeds, but also have been reported to possess multiple health-promoting effects, including antioxidant, anti-amnesic, anti-inflammatory, and anti-tumor activities. Thus, comprehensive metabolomic profiling of these metabolites is of key importance to help understand their biological activities, and other chemical biology features. In this context, this review will provide an update on the current technological platforms, and workflow associated with metabolomic studies on lotus seeds, as well as insights into the application of metabolomics for the improvement of food safety and quality, assisting breeding, and promotion of the study of metabolism and pharmacokinetics of lotus seeds; meanwhile it will also help explore new perspectives and outline future challenges in this fast-growing research subject. PMID: 27379154 [PubMed - as supplied by publisher]

Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress. Front Plant Sci. 2016;7:838 Authors: Martinez V, Mestre TC, Rubio F, Girones-Vilaplana A, Moreno DA, Mittler R, Rivero RM Abstract Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance. PMID: 27379130 [PubMed - as supplied by publisher]

Quantification of Carbohydrates in Grape Tissues Using Capillary Zone Electrophoresis. Front Plant Sci. 2016;7:818 Authors: Zhao L, Chanon AM, Chattopadhyay N, Dami IE, Blakeslee JJ Abstract Soluble sugars play an important role in freezing tolerance in both herbaceous and woody plants, functioning in both the reduction of freezing-induced dehydration and the cryoprotection of cellular constituents. The quantification of soluble sugars in plant tissues is, therefore, essential in understanding freezing tolerance. While a number of analytical techniques and methods have been used to quantify sugars, most of these are expensive and time-consuming due to complex sample preparation procedures which require the derivatization of the carbohydrates being analyzed. Analysis of soluble sugars using capillary zone electrophoresis (CZE) under alkaline conditions with direct UV detection has previously been used to quantify simple sugars in fruit juices. However, it was unclear whether CZE-based methods could be successfully used to quantify the broader range of sugars present in complex plant extracts. Here, we present the development of an optimized CZE method capable of separating and quantifying mono-, di-, and tri-saccharides isolated from plant tissues. This optimized CZE method employs a column electrolyte buffer containing 130 mM NaOH, pH 13.0, creating a current of 185 μA when a separation voltage of 10 kV is employed. The optimized CZE method provides limits-of-detection (an average of 1.5 ng/μL) for individual carbohydrates comparable or superior to those obtained using gas chromatography-mass spectrometry, and allows resolution of non-structural sugars and cell wall components (structural sugars). The optimized CZE method was successfully used to quantify sugars from grape leaves and buds, and is a robust tool for the quantification of plant sugars found in vegetative and woody tissues. The increased analytical efficiency of this CZE method makes it ideal for use in high-throughput metabolomics studies designed to quantify plant sugars. PMID: 27379118 [PubMed - as supplied by publisher]

Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus. J Transl Med. 2016;14(1):203 Authors: Pena MJ, Heinzel A, Rossing P, Parving HH, Dallmann G, Rossing K, Andersen S, Mayer B, Heerspink HJ Abstract BACKGROUND: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. METHODS: Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. RESULTS: In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p < 0.001) and improved prediction of UAE response on top of the clinical reference model (R(2) increase from 0.10 to 0.70; p < 0.001). In external validation, median change in UAE was -43 % [Q1-Q35: -63 to -23]. The classifier improved prediction of UAE response to losartan (R(2) increase from 0.20 to 0.59; p < 0.001). Specifically ADMA impacting eNOS activity appears to be a relevant factor in ARB response. CONCLUSIONS: A serum metabolite classifier was discovered and externally validated to significantly improve prediction of albuminuria response to ARBs in diabetes mellitus. PMID: 27378474 [PubMed - as supplied by publisher]

Extending the dynamic range in metabolomics experiments by automatic correction of peaks exceeding the detection limit. Anal Chem. 2016 Jul 5; Authors: Lisec J, Hoffmann F, Schmitt C, Jaeger C Abstract Metabolomics, the analysis of potentially all small molecules within a biological system, has become a valuable tool for biomarker identification and the elucidation of biological processes. While metabolites are often present in complex mixtures at extremely different concentrations, the dynamic range of available analytical methods to capture this variance is generally limited. Here, we show that gas chromatography coupled to atmospheric pressure chemical ionization mass spectrometry (GC APCI-MS), a state of the art analytical technology applied in metabolomics analyses, shows an average linear range (LR) of 2.39 orders of magnitude for a set of 62 metabolites from a representative compound mixture. We further developed a computational tool to extend this dynamic range on average by more than one order of magnitude, demonstrated with a dilution series of the compound mixture, using robust and automatic reconstruction of intensity values exceeding the detection limit. The tool is freely available as an R package (CorrectOverloadedPeaks) from CRAN (https://cran.r-project.org/) and can be incorporated in a metabolomics data processing pipeline facilitating large screening assays. PMID: 27377477 [PubMed - as supplied by publisher]

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 2016/07/05PubMed comprises more than 24 million 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.

Eosinophil polyunsaturated fatty acid metabolism and its potential control of inflammation and allergy. Allergol Int. 2016 Jun 29; Authors: Arita M Abstract Polyunsaturated fatty acids (PUFAs) exhibit a range of biological effects, many of which are mediated through the formation and actions of their bioactive metabolites. It is well appreciated that dietary PUFA balance affects inflammation and/or allergic diseases, and recent advances in liquid chromatography tandem mass spectrometry (LC-MS/MS)-based mediator lipidomics have revealed a potential link between PUFA metabolism and biological phenotypes. This review presents insights into the emerging roles of eosinophil PUFA metabolism in controlling inflammatory responses and its potential involvement in allergy control. PMID: 27371965 [PubMed - as supplied by publisher]

Evaluation of coverage, retention patterns, and selectivity of seven liquid chromatographic methods for metabolomics. Anal Bioanal Chem. 2016 Jul 1; Authors: Wernisch S, Pennathur S Abstract Liquid chromatography-mass spectrometry-based metabolomics studies require highly selective and efficient chromatographic techniques. Typically employed reversed-phase (RP) methods fail to target polar metabolites, but the introduction of hydrophilic interaction liquid chromatography (HILIC) is slow due to perceived issues of reproducibility and ruggedness and a limited understanding of the complex retention mechanisms. In this study, we present a comparison of the chromatographic performance of a traditional RP-C18 column with zwitterionic, amide-, alkyl diol-, and aminoalkyl-based HILIC and mixed-mode columns. Our metabolite library represents one of the largest analyte sets available and consists of 764 authentic metabolite standards, including amino acids, nucleotides, sugars, and other metabolites, representing all major biological pathways and commonly observed exogenous metabolites (drugs). The coverage, retention patterns, and selectivity of the individual methods are highly diverse even between conceptually related HILIC methods. Furthermore, we show that HILIC sorbents having highly orthogonal selectivity and specificity enhance the coverage of major metabolite groups in (semi-) targeted applications compared to RP. Finally, we discuss issues encountered in the analysis of biological samples based on the results obtained with human plasma extracts. Our results demonstrate that fast and highly reproducible separations on zwitterionic columns are feasible, but knowledge of analyte properties is essential to avoid chromatographic bias and exclusion of key analytes in metabolomics studies. Graphical Abstract The chromatographic parameters of 764 authentic metabolite standards provide the basis for a comparison of coverage, selectivity and orthogonality of 7 reversed-phase (RP), mixed-mode (MM) and hydrophilic interaction liquid chromatography (HILIC) methods. PMID: 27370688 [PubMed - as supplied by publisher]

Can atorvastatin with metformin change the natural history of prostate cancer as characterized by molecular, metabolomic, imaging and pathological variables? A randomized controlled trial protocol. Contemp Clin Trials. 2016 Jun 28; Authors: Roberts MJ, Yaxley JW, Coughlin GD, Gianduzzo TR, Esler RC, Dunglison NT, Chambers SK, Medcraft RJ, Chow CW, Schirra HJ, Richards RS, Kienzle N, Lu M, Brereton I, Samaratunga H, Perry-Keene J, Payton D, Oyama C, Doi SA, Lavin MF, Gardiner RA Abstract BACKGROUND: Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa. METHODS/DESIGN: This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy. Ethical approval was granted by the Royal Brisbane and Women's Hospital Human and The University of Queensland Medical Research Ethics Committees. Participants are being randomized into four groups: metformin with placebo; atorvastatin with placebo; metformin with atorvastatin; or placebo alone. Capsules are consumed for 8weeks, a duration selected as the most appropriate period in which histological and biochemical changes may be observed while allowing prompt treatment with curative intent of clinically significant PCa. At recruitment and prior to RP, participants provide blood, urine and seminal fluid. A subset of participants will undergo 7Tesla magnetic resonance spectroscopy to compare metabolites in-vivo with those in seminal fluid and biopsied tissue. The primary end point is biochemical progression, defined using biomarkers (serum prostate specific antigen; PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken alongside quality of life and psychosocial outcome assessments. DISCUSSION: This study is designed to assess the potential synergistic action of metformin and atorvastatin on PCa tumour biology. The results may determine simple methods of tumour modulation to reduce disease progression. PMID: 27370230 [PubMed - as supplied by publisher]

Lipidomics study of plasma phospholipid metabolism in early type 2 diabetes rats with ancient prescription Huang-Qi-San intervention by UPLC/Q-TOF-MS and correlation coefficient. Chem Biol Interact. 2016 Jun 28; Authors: Wu X, Zhang Y, Li WM, Rong XL, Feng YF Abstract Potential impact of lipid research has been increasingly realized both in disease treatment and prevention. An effective metabolomics approach based on ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) along with multivariate statistic analysis has been applied for investigating the dynamic change of plasma phospholipids compositions in early type 2 diabetic rats after the treatment of an ancient prescription of Chinese Medicine Huang-Qi-San. The exported UPLC/Q-TOF-MS data of plasma samples were subjected to SIMCA-P and processed by bioMark, mixOmics, Rcomdr packages with R software. A clear score plots of plasma sample groups, including normal control group (NC), model group (MC), positive medicine control group (Flu) and Huang-Qi-San group (HQS), were achieved by principal-components analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Biomarkers were screened out using student T test, principal component regression (PCR), partial least-squares regression (PLS) and important variable method (variable influence on projection, VIP). Structures of metabolites were identified and metabolic pathways were deduced by correlation coefficient. The relationship between compounds was explained by the correlation coefficient diagram, and the metabolic differences between similar compounds were illustrated. Based on KEGG database, the biological significances of identified biomarkers were described. The correlation coefficient was firstly applied to identify the structure and deduce the metabolic pathways of phospholipids metabolites, and the study provided a new methodological cue for further understanding the molecular mechanisms of metabolites in the process of regulating Huang-Qi-San for treating early type 2 diabetes. PMID: 27369808 [PubMed - as supplied by publisher]

Requirements and comparative analysis of reverse genetics for bluetongue virus (BTV) and African horse sickness virus (AHSV). Virol J. 2016;13(1):119 Authors: van Rijn PA, van de Water SG, Feenstra F, van Gennip RG Abstract BACKGROUND: Bluetongue virus (BTV) and African horse sickness virus (AHSV) are distinct arthropod borne virus species in the genus Orbivirus (Reoviridae family), causing the notifiable diseases Bluetongue and African horse sickness of ruminants and equids, respectively. Reverse genetics systems for these orbiviruses with their ten-segmented genome of double stranded RNA have been developed. Initially, two subsequent transfections of in vitro synthesized capped run-off RNA transcripts resulted in the recovery of BTV. Reverse genetics has been improved by transfection of expression plasmids followed by transfection of ten RNA transcripts. Recovery of AHSV was further improved by use of expression plasmids containing optimized open reading frames. RESULTS: Plasmids containing full length cDNA of the 10 genome segments for T7 promoter-driven production of full length run-off RNA transcripts and expression plasmids with optimized open reading frames (ORFs) were used. BTV and AHSV were rescued using reverse genetics. The requirement of each expression plasmid and capping of RNA transcripts for reverse genetics were studied and compared for BTV and AHSV. BTV was recovered by transfection of VP1 and NS2 expression plasmids followed by transfection of a set of ten capped RNAs. VP3 expression plasmid was also required if uncapped RNAs were transfected. Recovery of AHSV required transfection of VP1, VP3 and NS2 expression plasmids followed by transfection of capped RNA transcripts. Plasmid-driven expression of VP4, 6 and 7 was also needed when uncapped RNA transcripts were used. Irrespective of capping of RNA transcripts, NS1 expression plasmid was not needed for recovery, although NS1 protein is essential for virus propagation. Improvement of reverse genetics for AHSV was clearly demonstrated by rescue of several mutants and reassortants that were not rescued with previous methods. CONCLUSIONS: A limited number of expression plasmids is required for rescue of BTV or AHSV using reverse genetics, making the system much more versatile and generally applicable. Optimization of reverse genetics enlarge the possibilities to rescue virus mutants and reassortants, and will greatly benefit the control of these important diseases of livestock and companion animals. PMID: 27368544 [PubMed - as supplied by publisher]

Stable Isotope-Assisted Evaluation of Different Extraction Solvents for Untargeted Metabolomics of Plants. Int J Mol Sci. 2016;17(7) Authors: Doppler M, Kluger B, Bueschl C, Schneider C, Krska R, Delcambre S, Hiller K, Lemmens M, Schuhmacher R Abstract The evaluation of extraction protocols for untargeted metabolomics approaches is still difficult. We have applied a novel stable isotope-assisted workflow for untargeted LC-HRMS-based plant metabolomics , which allows for the first time every detected feature to be considered for method evaluation. The efficiency and complementarity of commonly used extraction solvents, namely 1 + 3 (v/v) mixtures of water and selected organic solvents (methanol, acetonitrile or methanol/acetonitrile 1 + 1 (v/v)), with and without the addition of 0.1% (v/v) formic acid were compared. Four different wheat organs were sampled, extracted and analysed by LC-HRMS. Data evaluation was performed with the in-house-developed MetExtract II software and R. With all tested solvents a total of 871 metabolites were extracted in ear, 785 in stem, 733 in leaf and 517 in root samples, respectively. Between 48% (stem) and 57% (ear) of the metabolites detected in a particular organ were found with all extraction mixtures, and 127 of 996 metabolites were consistently shared between all extraction agent/organ combinations. In aqueous methanol, acidification with formic acid led to pronounced pH dependency regarding the precision of metabolite abundance and the number of detectable metabolites, whereas extracts of acetonitrile-containing mixtures were less affected. Moreover, methanol and acetonitrile have been found to be complementary with respect to extraction efficiency. Interestingly, the beneficial properties of both solvents can be combined by the use of a water-methanol-acetonitrile mixture for global metabolite extraction instead of aqueous methanol or aqueous acetonitrile alone. PMID: 27367667 [PubMed - as supplied by publisher]

Applied metabolomics in drug discovery. Expert Opin Drug Discov. 2016 Jul 1;:1-12 Authors: Cuperlovic-Culf M, Culf AS Abstract INTRODUCTION: The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. AREAS COVERED: This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. EXPERT OPINION: Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads. PMID: 27366968 [PubMed - as supplied by publisher]

Untargeted Metabolomics Reveals Intervention Effects of Total Turmeric Extract in a Rat Model of Nonalcoholic Fatty Liver Disease. Evid Based Complement Alternat Med. 2016;2016:8495953 Authors: Wang Y, Niu M, Jia GL, Li RS, Zhang YM, Zhang CE, Meng YK, Cui HR, Ma ZJ, Li DH, Wang JB, Xiao XH Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease. Currently, there are no recognized medical therapies effective for NAFLD. Previous studies have demonstrated the effects of total turmeric extract on rats with NAFLD induced by high-fat diet. In this study, serum metabolomics was employed using UHPLC-Q-TOF-MS to elucidate the underlying mechanisms of HFD-induced NAFLD and the therapeutic effects of TE. Supervised orthogonal partial least-squares-discriminant analysis was used to discover differentiating metabolites, and pathway enrichment analysis suggested that TE had powerful combined effects of regulating lipid metabolism by affecting glycerophospholipid metabolism, glycerolipid metabolism, and steroid hormone biosynthesis signaling pathways. In addition, the significant changes in glycerophospholipid metabolism proteins also indicated that glycerophospholipid metabolism might be involved in the therapeutic effect of TE on NAFLD. Our findings not only supply systematic insight into the mechanisms of NAFLD but also provide a theoretical basis for the prevention or treatment of NAFLD. PMID: 27366193 [PubMed]

Integrated analysis of gene expression from carbon metabolism, proteome and metabolome, reveals altered primary metabolism in Eucalyptus grandis bark, in response to seasonal variation. BMC Plant Biol. 2016;16(1):149 Authors: Budzinski IG, Moon DH, Morosini JS, Lindén P, Bragatto J, Moritz T, Labate CA Abstract BACKGROUND: Seasonal variation is presumed to play an important role in the regulation of tree growth, especially for Eucalyptus grandis, a fast-growing tree. This variation may induce changes in the whole tree at transcriptional, protein and metabolite levels. Bark represents an important group of tissues that protect trees from desiccation and pathogen attack, and it has been identified as potential feedstock for lignocellulosic derived biofuels. Despite the growing interest, little is known about the molecular mechanisms that regulates bark metabolism, particularly in tropical countries. RESULTS: In this study we report the changes observed in the primary metabolism of E. grandis bark during two contrasting seasons in Brazil, summer (wet) and winter (dry), through the combination of transcripts (RT-qPCR), proteome (2-DE gels) and metabolome (GC-MS) analysis, in an integrated manner. Twenty-four genes, involved in carbon metabolism, were analyzed in the two seasons. Eleven were up-regulated in summer, three were up-regulated in winter and ten did not show statistical differences in the expression pattern. The proteomic analysis using 2-DE gels showed 77 proteins expressing differences in abundance, with 38 spots up-regulated in summer and 37 in winter. Different metabolites significantly accumulated during winter. CONCLUSIONS: This study revealed a metabolic reconfiguration in the primary metabolism of E. grandis bark, triggered by seasonal variation. Transcripts and protein data suggests that during winter carbohydrate formation seems to be favored by tree metabolism. Glucose, fructose and sucrose accumulated at significant levels during the winter. PMID: 27364638 [PubMed - in process]

Metabolomics reveals differences between three daidzein metabolizing phenotypes in adults with cardiometabolic risk factors. Mol Nutr Food Res. 2016 Jul 1; Authors: Reverri EJ, Slupsky CM, Mishchuk DO, Steinberg FM Abstract SCOPE: The soy isoflavone, daidzein, is metabolized by gut microbiota to O-desmethylangolensin (ODMA) and/or equol. Producing equol is postulated as a contributing factor for the beneficial effects of soy. METHODS AND RESULTS: This randomized, controlled, crossover design used an untargeted metabolomic approach to assess the metabolic profile of different daidzein metabolizers. Adults (n = 17) with cardiometabolic risk factors received soy nuts or control food for four-weeks, separated by a two-week washout. No significant differences were detected pre- and post-intervention and between interventions. Examination of the ability to metabolize daidzein revealed three groups: ODMA only producers (n = 4), equol+ODMA producers (n = 8), and non-producers (n = 5). Analysis of the serum metabolome revealed non-producers could be distinguished from ODMA-only and equol+ODMA producers. Differences between these phenotypes were related to obesity and metabolic risk (methionine, asparagine, and trimethylamine) with equol+ODMA producers having lower concentrations, yet paradoxically higher pro-inflammatory cytokines. In urine, non-producers clustered with ODMA producers, and were distinct from equol+ODMA producers. Urinary metabolite profiles revealed significantly higher excretion of fumarate and 2-oxoglutarate, as well as pyroglutamate, alanine, and the gut microbial metabolite dimethylamine in equol+ODMA producers. CONCLUSION: These results emphasize that the serum and urine metabolomes are distinct based on the ability to metabolize isoflavones. This article is protected by copyright. All rights reserved. PMID: 27364093 [PubMed - as supplied by publisher]

Natural variation of root exudates in Arabidopsis thaliana-linking metabolomic and genomic data. Sci Rep. 2016;6:29033 Authors: Mönchgesang S, Strehmel N, Schmidt S, Westphal L, Taruttis F, Müller E, Herklotz S, Neumann S, Scheel D Abstract Many metabolomics studies focus on aboveground parts of the plant, while metabolism within roots and the chemical composition of the rhizosphere, as influenced by exudation, are not deeply investigated. In this study, we analysed exudate metabolic patterns of Arabidopsis thaliana and their variation in genetically diverse accessions. For this project, we used the 19 parental accessions of the Arabidopsis MAGIC collection. Plants were grown in a hydroponic system, their exudates were harvested before bolting and subjected to UPLC/ESI-QTOF-MS analysis. Metabolite profiles were analysed together with the genome sequence information. Our study uncovered distinct metabolite profiles for root exudates of the 19 accessions. Hierarchical clustering revealed similarities in the exudate metabolite profiles, which were partly reflected by the genetic distances. An association of metabolite absence with nonsense mutations was detected for the biosynthetic pathways of an indolic glucosinolate hydrolysis product, a hydroxycinnamic acid amine and a flavonoid triglycoside. Consequently, a direct link between metabolic phenotype and genotype was detected without using segregating populations. Moreover, genomics can help to identify biosynthetic enzymes in metabolomics experiments. Our study elucidates the chemical composition of the rhizosphere and its natural variation in A. thaliana, which is important for the attraction and shaping of microbial communities. PMID: 27363486 [PubMed - in process]

Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array. J Extracell Vesicles. 2016;5:31209 Authors: Welton JL, Brennan P, Gurney M, Webber JP, Spary LK, Carton DG, Falcón-Pérez JM, Walton SP, Mason MD, Tabi Z, Clayton A Abstract Proteomics analysis of biofluid-derived vesicles holds enormous potential for discovering non-invasive disease markers. Obtaining vesicles of sufficient quality and quantity for profiling studies has, however, been a major problem, as samples are often replete with co-isolated material that can interfere with the identification of genuine low abundance, vesicle components. Here, we used a combination of ultracentrifugation and size-exclusion chromatography to isolate and analyse vesicles of plasma or urine origin. We describe a sample-handling workflow that gives reproducible, quality vesicle isolations sufficient for subsequent protein profiling. Using a semi-quantitative aptamer-based protein array, we identified around 1,000 proteins, of which almost 400 were present at comparable quantities in plasma versus urine vesicles. Significant differences were, however, apparent with elements like HSP90, integrin αVβ5 and Contactin-1 more prevalent in urinary vesicles, while hepatocyte growth factor activator, prostate-specific antigen-antichymotrypsin complex and many others were more abundant in plasma vesicles. This was also applied to a small set of specimens collected from men with metastatic prostate cancer, highlighting several proteins with the potential to indicate treatment refractory disease. The study provides a practical platform for furthering protein profiling of vesicles in prostate cancer, and, hopefully, many other disease scenarios. PMID: 27363484 [PubMed]

Related Articles Essential Role of Acyl-ACP Synthetase in Acclimation of the Cyanobacterium Synechococcus elongatus Strain PCC 7942 to High-Light Conditions. Plant Cell Physiol. 2015 Aug;56(8):1608-15 Authors: Takatani N, Use K, Kato A, Ikeda K, Kojima K, Aichi M, Maeda S, Omata T Abstract Most organisms capable of oxygenic photosynthesis have an aas gene encoding an acyl-acyl carrier protein synthetase (Aas), which activates free fatty acids (FFAs) via esterification to acyl carrier protein. Cyanobacterial aas mutants are often used for studies aimed at photosynthetic production of biofuels because the mutation leads to intracellular accumulation of FFAs and their secretion into the external medium, but the physiological significance of the production of FFAs and their recycling involving Aas has remained unclear. Using an aas-deficient mutant of Synechococcus elongatus strain PCC 7942, we show here that remodeling of membrane lipids is activated by high-intensity light and that the recycling of FFAs is essential for acclimation to high-light conditions. Unlike wild-type cells, the mutant cells could not increase their growth rate as the light intensity was increased from 50 to 400 µmol photons m(-2) s(-1), and the high-light-grown mutant cells accumulated FFAs and the lysolipids derived from all the four major classes of membrane lipids, revealing high-light-induced lipid deacylation. The high-light-grown mutant cells showed much lower PSII activity and Chl contents as compared with the wild-type cells or low-light-grown mutant cells. The loss of Aas accelerated photodamage of PSII but did not affect the repair process of PSII, indicating that PSII is destabilized in the mutant. Thus, Aas is essential for acclimation of the cyanobacterium to high-light conditions. The relevance of the present finding s to biofuel production using cyanobacteria is discussed. PMID: 26063393 [PubMed - indexed for MEDLINE]