PubMed

Related Articles Systems level metabolic phenotype of methotrexate administration in the context of non-alcoholic steatohepatitis in the rat. Toxicol Sci. 2014 Nov;142(1):105-16 Authors: Kyriakides M, Hardwick RN, Jin Z, Goedken MJ, Holmes E, Cherrington NJ, Coen M Abstract Adverse drug reactions (ADRs) represent a significant clinical challenge with respect to patient morbidity and mortality. We investigated the hepatotoxicity and systems level metabolic phenotype of methotrexate (MTX) in the context of a prevalent liver disease; non-alcoholic steatohepatitis (NASH). A nuclear magnetic resonance spectroscopic-based metabonomic approach was employed to analyze the metabolic consequences of MTX (0, 10, 40, and 100 mg/kg) in the urine and liver of healthy rats (control diet) and in a model of NASH (methionine-choline deficient diet). Histopathological analysis confirmed baseline (0 mg/kg) liver necrosis, liver inflammation, and lipid accumulation in the NASH model. Administration of MTX (40 and 100 mg/kg) led to liver necrosis in the control cohort, whereas the NASH cohort also displayed biliary hyperplasia and liver fibrosis (100 mg/kg), providing evidence of the synergistic effect of MTX and NASH. The complementary hepatic and urinary metabolic phenotypes of the NASH model, at baseline, revealed perturbation of multiple metabolites associated with oxidative and energetic stress, and folate homeostasis. Administration of MTX in both diet cohorts showed dose-dependent metabolic consequences affecting gut microbial, energy, nucleobase, nucleoside, and folate metabolism. Furthermore, a unique panel of metabolic changes reflective of the synergistic effect of MTX and NASH was identified, including the elevation of hepatic phenylalanine, urocanate, acetate, and both urinary and hepatic formiminoglutamic acid. This systems level metabonomic analysis of the hepatotoxicity of MTX in the context of NASH provided novel mechanistic insight of potential wider clinical relevance for further understanding the role of liver pathology as a risk factor for ADRs. PMID: 25145655 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of the resurrection plant Haberlea rhodopensis during desiccation and recovery. Physiol Plant. 2014 Dec;152(4):675-87 Authors: Moyankova D, Mladenov P, Berkov S, Peshev D, Georgieva D, Djilianov D Abstract Desiccation tolerance is among the most important parameters for crop improvement under changing environments. Resurrection plants are useful models for both theoretical and practical studies. We performed metabolite profiling via gas chromatography coupled with mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) and analyzed the antioxidant capacity of the endemic resurrection plant Haberlea rhodopensis at desiccation and recovery. More than 100 compounds were evaluated. Stress response included changes in both primary and secondary metabolic pathways. The high amounts of the specific glycoside myconoside and some phenolic acids - e.g. syringic and dihydrocaffeic acid under normal conditions tend to show their importance for the priming of H. rhodopensis to withstand severe desiccation and oxidative stress. The accumulation of sucrose (resulting from starch breakdown), total phenols, β-aminoisobutyric acid, β-sitosterol and α-tocopherol increased up to several times at later stages of desiccation. Extracts of H. rhodopensis showed high antioxidant capacity at stress and normal conditions. Myconoside was with the highest antioxidant properties among tested phenolic compounds. Probably, the evolution of resurrection plants under various local environments has resulted in unique desiccation tolerance with specific metabolic background. In our case, it includes the accumulation of a relatively rare compound (myconoside) that contributes alone and together with other common metabolites. Further systems biology studies on the involvement of carbohydrates, phenolic acids and glycosides in the desiccation tolerance and antioxidant capacity of H. rhodopensis will definitely help in achieving the final goal - improving crop drought tolerance. PMID: 24735127 [PubMed - indexed for MEDLINE]

Related Articles Phosphorus and iron deficiencies induce a metabolic reprogramming and affect the exudation traits of the woody plant Fragaria× ananassa. J Exp Bot. 2015 Jul 17; Authors: Valentinuzzi F, Pii Y, Vigani G, Lehmann M, Cesco S, Mimmo T Abstract Strawberries are a very popular fruit among berries, for both their commercial and economic importance, but especially for their beneficial effects for human health. However, their bioactive compound content is strictly related to the nutritional status of the plant and might be affected if nutritional disorders (e.g. Fe or P shortage) occur. To overcome nutrient shortages, plants evolved different mechanisms, which often involve the release of root exudates. The biochemical and molecular mechanisms underlying root exudation and its regulation are as yet still poorly known, in particular in woody crop species. The aim of this work was therefore to characterize the pattern of root exudation of strawberry plants grown in either P or Fe deficiency, by investigating metabolomic changes of root tissues and the expression of genes putatively involved in exudate extrusion. Although P and Fe deficiencies differentially affected the total metabolism, some metabolites (e.g. raffinose and galactose) accumulated in roots similarly under both conditions. Moreover, P deficiency specifically affected the content of galactaric acid, malic acid, lysine, proline, and sorbitol-6-phosphate, whereas Fe deficiency specifically affected the content of sucrose, dehydroascorbic acid, galactonate, and ferulic acid. At the same time, the citrate content did not change in roots under both nutrient deficiencies with respect to the control. However, a strong release of citrate was observed, and it increased significantly with time, being +250% and +300% higher in Fe- and P-deficient plants, respectively, compared with the control. Moreover, concomitantly, a significant acidification of the growth medium was observed in both treatments. Gene expression analyses highlighted for the first time that at least two members of the multidrug and toxic compound extrusion (MATE) transporter family and one member of the plasma membrane H(+)-ATPase family are involved in the response to both P and Fe starvation in strawberry plants. PMID: 26188206 [PubMed - as supplied by publisher]

Related Articles Low-dose cadmium causes metabolic and genetic dysregulation associated with fatty liver disease in mice. Toxicol Sci. 2015 Jul 16; Authors: Go YM, Sutliff RL, Chandler JD, Khalidur R, Kang BY, Anania FA, Orr M, Hao L, Fowler BA, Jones DP Abstract Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that non-alcoholic fatty liver disease (NAFLD), common in US adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/L) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd-treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis. PMID: 26187450 [PubMed - as supplied by publisher]

Related Articles Plasma-metabolite-biomarkers for the therapeutic response in depressed patients by the traditional Chinese medicine formula Xiaoyaosan: A (1)H NMR-based metabolomics approach. J Affect Disord. 2015 Jul 7;185:156-163 Authors: Liu CC, Wu YF, Feng GM, Gao XX, Zhou YZ, Hou WJ, Qin XM, Du GH, Tian JS Abstract BACKGROUND: Depression is one of the most prevalent and serious mental disorders. Xiaoyaosan, a well-known Chinese prescription, has been widely used for the treatment of depression in China. Both clinical studies and animal experiments indicate that Xiaoyaosan has an obvious antidepressant activity. Additionally, a large number of candidate biomarkers have emerged that can be used for early disease detection and for monitoring ongoing treatment response to therapy because of their correlations with the characteristics of the disease. However, there have been few reports on biomarkers that measure the treatment response to the clinical use of Xiaoyaosan using a metabolomics approach. The current study is aimed at discovering biomarkers and biochemical pathways to facilitate the diagnosis of depression and the efficient evaluation of Xiaoyaosan using plasma metabolomics profiles based on (1)H NMR. METHODS: Sixteen depressed patients diagnosed by standard methods (HAMD and CGI-SI) and sixteen healthy volunteers were recruited. (1)H NMR-based metabolomics techniques and multivariate statistical methods were used to analyze the plasma metabolites of the depressed patients before and after treatment and to compare them with healthy controls. RESULTS: The plasma levels of trimethylamine oxide, glutamine and lactate in depressed patients increased significantly (p≤0.05) compared with healthy controls, whereas the levels of phenylalanine, valine, alanine, glycine, leucine, citrate, choline, lipids and glucose decreased significantly (p≤0.05). Additionally, alanine, choline, trimethylamine oxide, glutamine, lactate and glucose were returned to normal levels after Xiaoyaosan treatment. These statistically significant perturbations are involved in energy metabolism, amino acid metabolism and gut microbiota metabolism. LIMITATIONS: Additional experimentation with gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) is required to confirm our findings. CONCLUSIONS: Application of these biomarkers in clinical practice may help to optimize the diagnosis of depression and to evaluate the efficacy of Xiaoyaosan. Metabolomics is promising as a biomarker discovery tool. PMID: 26186531 [PubMed - as supplied by publisher]

Related Articles Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling. J Nat Prod. 2015 Jul 17; Authors: Lovelace ES, Wagoner J, MacDonald J, Bammler T, Bruckner J, Brownell J, Beyer RP, Zink EM, Kim YM, Kyle JE, Webb-Robertson BM, Waters KM, Metz TO, Farin F, Oberlies NH, Polyak SJ Abstract Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed silymarin suppression of glycolytic, tricarboxylic acid (TCA) cycle, and amino acid metabolism. Anti-inflammatory effects arose with prolonged (i.e., 24 h) silymarin exposure, with suppression of multiple pro-inflammatory mRNAs and signaling pathways including nuclear factor kappa B (NF-κB) and forkhead box O (FOXO). Studies with murine knock out cells revealed that silymarin inhibition of both mTOR and NF-κB was partially AMPK dependent, whereas silymarin inhibition of mTOR required DDIT4. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Thus, natural products activate stress and repair responses that culminate in an anti-inflammatory cellular phenotype. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation. PMID: 26186142 [PubMed - as supplied by publisher]

Related Articles Lack of soluble fiber drives diet-induced adiposity in mice. Am J Physiol Gastrointest Liver Physiol. 2015 Jul 16;:ajpgi.00172.2015 Authors: Chassaing B, Miles-Brown JP, Pellizzon M, Ulman E, Ricci M, Zhang L, Patterson AD, Vijay-Kumar M, Gewirtz AT Abstract BACKGROUND: Diet-induced obesity is often modeled by comparing mice fed high-fat diet (HFD), which is made from purified ingredients, vs. normal chow diet (NCD), which is a low-fat assemblage of relatively unrefined plant and animal products. The mechanism by which HFD promotes adiposity is complex but thought to involve low-grade inflammation and altered gut microbiota. GOAL: Investigate the extent to which HFD-induced adiposity is driven by fat content vs. other factors that differentiate HFD vs. NCD. METHODS: Mice were fed NCD, HFD, or other compositionally-defined diets (CDD), designed to mimic NCD and/or explore the role of HFD components. A range of metabolic parameters reflecting low-grade inflammation and adiposity were assayed. RESULTS: Relative to NCD, HFD, and to a lesser but nonetheless significant extent, CDD induced increased adiposity indicating both lipid content and other aspects of HFD are obesogenic. Moreover, HFD and CDD induced a rapid and marked loss of cecal and colonic mass. Such CDD-induced effects were not affected by adjusting dietary protein levels/types but could be largely eliminated by exchanging insoluble fiber (cellulose) for soluble fiber (inulin). Replacing cellulose with inulin in HFD also protected mice against decreased intestinal mass, hyperphagia and increased adiposity. Such beneficial effects of inulin were microbiota-dependent, correlated with elevated fecal short-chain fatty acid (SCFA) levels analyzed via 1H-NMR based metabolomics, and were partially recapitulated by administration of SCFA. CONCLUSIONS: HFD-induced obesity is strongly promoted by its lack of soluble fiber, which supports microbiota-mediated intestinal tissue homeostasis that prevents inflammation driving obesity and metabolic syndrome. PMID: 26185332 [PubMed - as supplied by publisher]

Related Articles FRET-based genetically-encoded sensors for quantitative monitoring of metabolites. Biotechnol Lett. 2015 Jul 17; Authors: Mohsin M, Ahmad A, Iqbal M Abstract Neighboring cells in the same tissue can exist in different states of dynamic activities. After genomics, proteomics and metabolomics, fluxomics is now equally important for generating accurate quantitative information on the cellular and sub-cellular dynamics of ions and metabolite, which is critical for functional understanding of organisms. Various spectrometry techniques are used for monitoring ions and metabolites, although their temporal and spatial resolutions are limited. Discovery of the fluorescent proteins and their variants has revolutionized cell biology. Therefore, novel tools and methods targeting sub-cellular compartments need to be deployed in specific cells and targeted to sub-cellular compartments in order to quantify the target-molecule dynamics directly. We require tools that can measure cellular activities and protein dynamics with sub-cellular resolution. Biosensors based on fluorescence resonance energy transfer (FRET) are genetically encoded and hence can specifically target sub-cellular organelles by fusion to proteins or targetted sequences. Since last decade, FRET-based genetically encoded sensors for molecules involved in energy production, reactive oxygen species and secondary messengers have helped to unravel key aspects of cellular physiology. This review, describing the design and principles of sensors, presents a database of sensors for different analytes/processes, and illustrate examples of application in quantitative live cell imaging. PMID: 26184603 [PubMed - as supplied by publisher]

Related Articles Phospholipid fatty acid profiling of microbial communities - a review of interpretations and recent applications. J Appl Microbiol. 2015 Jul 15; Authors: Willers C, Jansen van Rensburg PJ, Claassens S Abstract Profiling of microbial communities in environmental samples often utilizes phospholipid fatty acid (PLFA) analysis. This method has been used for more than 35 years and is still popular as a means to characterize microbial communities in a diverse range of environmental matrices. This review examines the various recent applications of PLFA analysis in environmental studies with specific reference to the interpretation of the PLFA results. It is evident that interpretations of PLFA results do not always correlate between different investigations. These discrepancies in interpretation and their subsequent applications to environmental studies are discussed. However, in spite of limitations to the manner in which PLFA data is applied, the approach remains one with great potential for improving our understanding of the relationship between microbial populations and the environment. This review highlights the caveats and provides suggestions towards the practicable application of PLFA data interpretation. This article is protected by copyright. All rights reserved. PMID: 26184497 [PubMed - as supplied by publisher]

Related Articles A Metabolomic Approach to Target Compounds from the Asteraceae Family for Dual COX and LOX Inhibition. Metabolites. 2015;5(3):404-30 Authors: Chagas-Paula DA, Zhang T, Da Costa FB, Edrada-Ebel R Abstract The application of metabolomics in phytochemical analysis is an innovative strategy for targeting active compounds from a complex plant extract. Species of the Asteraceae family are well-known to exhibit potent anti-inflammatory (AI) activity. Dual inhibition of the enzymes COX-1 and 5-LOX is essential for the treatment of several inflammatory diseases, but there is not much investigation reported in the literature for natural products. In this study, 57 leaf extracts (EtOH-H2O 7:3, v/v) from different genera and species of the Asteraceae family were tested against COX-1 and 5-LOX while HPLC-ESI-HRMS analysis of the extracts indicated high diversity in their chemical compositions. Using O2PLS-DA (R2 > 0.92; VIP > 1 and positive Y-correlation values), dual inhibition potential of low-abundance metabolites was determined. The O2PLS-DA results exhibited good validation values (cross-validation = Q2 > 0.7 and external validation = P2 > 0.6) with 0% of false positive predictions. The metabolomic approach determined biomarkers for the required biological activity and detected active compounds in the extracts displaying unique mechanisms of action. In addition, the PCA data also gave insights on the chemotaxonomy of the family Asteraceae across its diverse range of genera and tribes. PMID: 26184333 [PubMed]

Related Articles High-Resolution Metabolomics: Review of the Field and Implications for Nursing Science and the Study of Preterm Birth. Biol Res Nurs. 2015 Jul 16; Authors: Li S, Dunlop AL, Jones DP, Corwin EJ Abstract Most complex health conditions do not have a single etiology but rather develop from exposure to multiple risk factors that interact to influence individual susceptibility. In this review, we discuss the emerging field of metabolomics as a means by which metabolic pathways underlying a disease etiology can be exposed and specific metabolites can be identified and linked, ultimately providing biomarkers for early detection of disease onset and new strategies for intervention. We present the theoretical foundation of metabolomics research, the current methods employed in its conduct, and the overlap of metabolomics research with other "omic" approaches. As an exemplar, we discuss the potential of metabolomics research in the context of deciphering the complex interactions of the maternal-fetal exposures that underlie the risk of preterm birth, a condition that accounts for substantial portions of infant morbidity and mortality and whose etiology and pathophysiology remain incompletely defined. We conclude by providing strategies for including metabolomics research in future nursing studies for the advancement of nursing science. PMID: 26183181 [PubMed - as supplied by publisher]

Related Articles Identifying individual differences of fluoxetine response in juvenile rhesus monkeys by metabolite profiling. Transl Psychiatry. 2014;4:e478 Authors: He Y, Hogrefe CE, Grapov D, Palazoglu M, Fiehn O, Turck CW, Golub MS Abstract Fluoxetine is the only psychopharmacological agent approved for depression by the US Food and Drug Administration for children and is commonly used therapeutically in a variety of neurodevelopmental disorders. Therapeutic response shows high individual variability, and severe side effects have been observed. In the current study we set out to identify biomarkers of response to fluoxetine as well as biomarkers that correlate with impulsivity, a measure of reward delay behavior and potential side effect of the drug, in juvenile male rhesus monkeys. The study group was also genotyped for polymorphisms of monoamine oxidase A (MAOA), a gene that has been associated with psychiatric disorders. We used peripheral metabolite profiling of blood and cerebrospinal fluid (CSF) from animals treated daily with fluoxetine or vehicle for one year. Fluoxetine response metabolite profiles and metabolite/reward delay behavior associations were evaluated using multivariate analysis. Our analyses identified a set of plasma and CSF metabolites that distinguish fluoxetine- from vehicle-treated animals and metabolites that correlate with impulsivity. Some metabolites displayed an interaction between fluoxetine and MAOA genotype. The identified metabolite biomarkers belong to pathways that have important functions in central nervous system physiology. Biomarkers of response to fluoxetine in the normally functioning brain of juvenile nonhuman primates may aid in finding predictors of response to treatment in young psychiatric populations and in progress toward the realization of a precision medicine approach in the area of neurodevelopmental disorders. PMID: 25369145 [PubMed - indexed for MEDLINE]

Related Articles Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite. J Biochem. 2014 Dec;156(6):315-21 Authors: Yokokura Y, Isobe Y, Matsueda S, Iwamoto R, Goto T, Yoshioka T, Urabe D, Inoue M, Arai H, Arita M Abstract Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as D-series resolvins, protectin and maresin. Here, we analysed the lipids in inflammatory exudates using liquid chromatography-tandem mass spectrometry and identified a novel DHA metabolite, 14,20-dihydroxy-DHA (14,20-diHDHA) and showed that it is biosynthesized by eosinophils through the 12/15-lipoxygenase pathway. The chemical structure of the dominant 14,20-diHDHA isomer, which is endogenously biosynthesized by eosinophils, was identified as 14S,20R-diHDHA using chemically synthesized stereoisomers. Nanogram doses of 14,20-diHDHA displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The in vivo formation and potent anti-inflammatory action of 14,20-diHDHA may contribute to the protective effects of DHA. PMID: 25012818 [PubMed - indexed for MEDLINE]

Related Articles Postprandial Plasma Phospholipids in Men Are Influenced by the Source of Dietary Fat. J Nutr. 2015 Jul 15; Authors: Meikle PJ, Barlow CK, Mellett NA, Mundra PA, Bonham MP, Larsen A, Cameron-Smith D, Sinclair A, Nestel PJ, Wong G Abstract BACKGROUND: Postprandial lipemia represents a risk factor for chronic diseases, including type 2 diabetes. Little is known about the effect of dietary fat on the plasma lipidome in the postprandial period. OBJECTIVE: The objective of this study was to assess the effect of dairy fat and soy oil on circulating postprandial lipids in men. METHODS: Men, 40-60 y old, nonsmokers (n = 16), were randomly assigned in a crossover design to consume 2 breakfast meals of dairy-based or soy oil-based foods. The changes in the plasma lipidome during a 4-h postprandial period were analyzed with electrospray ionization tandem mass spectrometry and included 316 lipid species in 23 classes and subclasses, representing sphingolipids, phospholipids, glycerolipids, and sterols. RESULTS: Nonparametric Friedman tests showed significant changes in multiple plasma lipid classes, subclasses, and species in the postprandial period after both dairy and soy meals. No difference was found in the triglyceridemias after each meal. However, 6 endogenous lipid classes increased after dairy but decreased after soy (P < 0.05), including ether-linked phospholipids and plasmalogens and sphingomyelin (not present in soy), dihexosylceramide, and GM3 ganglioside. Phosphatidylcholine and phosphatidylinositol were not affected by the soy meal but were significantly elevated after the dairy meal (8.3% and 16%, respectively; P < 0.05). CONCLUSIONS: The changes in postprandial plasma phospholipids in men relate to the diet composition and the relative size of the endogenous phospholipid pools. Despite similar lipemic responses as measured by changes in triglyceride concentrations, the differential responses between dairy and soy meals derived through lipidomic analysis of phospholipids suggest differences in the metabolism of soybean oil and dairy fat. The increased concentrations of plasmalogens, with potential antioxidant capacity, in the postprandial period after dairy but not soy meals may represent a further important difference in the response to these sources of fat. The trial was registered at www.anzctr.org.au as ACTRN12610000562077. PMID: 26180244 [PubMed - as supplied by publisher]

Related Articles Development and validation of a HILIC- MS/MS multi-targeted method for metabolomics applications. Electrophoresis. 2015 Jul 14; Authors: Virgiliou C, Sampsonidis I, Gika HG, Raikos N, Theodoridis GA Abstract The paper reports the development of a multi-analyte method and its application in metabolic profiling of biological fluids. The initial aim of the method was the quantification of metabolites existing in cell culture medium used in in-vitro fertilisation (IVF) and in other biological fluids related to embryo growth. Since most of these analytes are polar primary metabolites a hydrophilic interaction liquid chromatography (HILIC) system was selected. The analytical system comprised Ultra (High) performance liquid chromatography (UHPLC) with detection on a triple quadrupole mass spectrometer operating in both positive and negative modes. Mobile phase and gradient elution conditions were studied with the aim to achieve the highest coverage of metabolic space in a single injection namely the largest number of analytes that could be detected and quantified. The developed method provides absolute quantitation of ca. 100 metabolites belonging to key metabolite classes such as sugars, aminoacids, nucleotides, organic acids and amines. Following validation, the method was applied for the metabolic profiling of hundreds of samples of spent culture medium originating from human IVF procedures and several hundreds of biological samples such as amniotic fluid, human urine and blood serum from pregnant women. The bioanalytical end-point was to provide assistance in the process of embryo transfer and improving IVF success rates but also to provide insight in complications related to the subsequent embryo growth during pregnancy. This article is protected by copyright. All rights reserved. PMID: 26180020 [PubMed - as supplied by publisher]

Related Articles Defensive and adverse energy-related molecular responses precede tris (1, 3-dichloro-2-propyl) phosphate cytotoxicity. J Appl Toxicol. 2015 Jul 15; Authors: Zhang J, Williams TD, Chipman JK, Viant MR Abstract To understand the potentially adverse effects of human exposure to tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) and explore the underlying molecular mechanisms, combined transcriptomic and metabolomic approaches were employed to investigate the molecular responses of two human cell lines exposed to different concentrations of TDCIPP. Comparative analyses of transcriptional and metabolic profiles of HepG2/C3A and A549 cells were performed after exposure to 1, 10 and 100 μM TDCIPP for 24 and 72 h. Stress responses (e.g. xenobiotic metabolism and ABC transporter pathways) were observed at the transcriptional level after 24-h exposure to a sub-cytotoxic concentration (10 μM). Transcription of an energy metabolism-related pathway (oxidative phosphorylation) was down-regulated more severely at 100 μM TDCIPP exposure, accompanied by the suppression of pathways relevant to cell proliferation (e.g. cell cycle and DNA replication), while no significant cytotoxic effects were observed. Functional metabolic changes were observed after 72 h in HepG2/C3A cells exposed to 100 μM TDCIPP that corresponded to changes detected at the transcriptional level after 24 h. Taken together, defensive responses to chemical exposure and energy-related changes both precede the cytotoxic effects of TDCIPP in HepG2/C3A cells. Copyright © 2015 John Wiley & Sons, Ltd. PMID: 26179874 [PubMed - as supplied by publisher]

Related Articles Serum metabolomics analysis reveals changes in signalling lipids in breast cancer patients. Biomed Chromatogr. 2015 Jul 14; Authors: Cui M, Wang Q, Chen G Abstract Breast cancer is the most commonly diagnosed cancer and one of the leading causes of cancer death among women worldwide. It is a biologically variable disease with different molecular subtypes, risk factors, clinical behaviours, and responses to treatment. Better understanding on the molecular changes associated with each subtype is essential for identifying new therapeutic targets and markers for the monitoring of treatment responses. In this pilot study, mass spectrometry-based metabolic profiling was performed to characterize the changes in serum profiles of patients with invasive ductal carcinoma (IDC)-the most common type of breast cancer. Serum samples from 20 IDC patients and 20 age- and gender-matched healthy subjects were analyzed and 15 differentially expressed metabolites were identified. These metabolites are involved in several metabolic pathways such as sphingolipid metabolism, phospholipid metabolism and fatty acid β-oxidation. Among these, two classes of signalling lipids, lysophosphatidylethanolamine (LPE) and ceramide, may play an important role in IDC development and progression. This study demonstrates metabolic profiling as a promising tool for finding disease biomarkers and our findings provide new directions for further mechanistic studies on the pathology of IDC. This article is protected by copyright. All rights reserved. PMID: 26179699 [PubMed - as supplied by publisher]

Related Articles Compartment-specific metabolomics for CHO reveals that ATP pools in mitochondria are much lower than in cytosol. Biotechnol J. 2015 Jul 14; Authors: Matuszczyk JC, Teleki A, Pfizenmaier J, Takors R Abstract Mammalian cells show a compartmented metabolism. Getting access to subcellular me-tabolite pools is of high interest to understand the cells' metabolomic state. There-fore a protocol is developed and applied for monitoring compartment-specific metabolite and nucleotide pool sizes in chinese hamster ovary (CHO) cells. The approach consists of a subtracting filtering method separating cytosolic components from physically intact mito-chondrial compartments. The internal standards glucose-6 phosphate and cis aconitate were chosen to quantify cytosolic secession and mitochondrial membrane integrity. Ex-tracts of related fractions were studied by liquid chromatography- isotope dilution mass spectrometry for the absolute quantification of a subset of glycolytic and tricarboxylic acid cycle intermediates together with the adenylate nucleotides ATP, ADP and AMP. The ap-plication of the protocol revealed highly dynamic changes in the related pool sizes as a function of distinct cultivation periods of IgG1 producing CHO cells. Mitochondrial and cytosolic pool dynamics were in agreement with anticipated metabolite pools of inde-pendent studies. The analysis of adenosine phosphate levels unraveled significantly higher ATP levels in the cytosol leading to the hypothesis that mitochondria predominately serve for fueling ATP into the cytosol where it is tightly controlled at physiological adenylate energy charges about 0.9. PMID: 26179617 [PubMed - as supplied by publisher]

Related Articles Warming and drought differentially influence the production and resorption of elemental and metabolic nitrogen pools in Quercus rubra. Glob Chang Biol. 2015 Jul 14; Authors: Suseela V, Tharayil N, Xing B, Dukes JS Abstract The process of nutrient retranslocation from plant leaves during senescence subsequently affects both plant growth and soil nutrient cycling; changes in either of these could potentially feed back to climate change. Although elemental nutrient resorption has been shown to respond modestly to temperature and precipitation, we know remarkably little about the influence of increasing intensities of drought and warming on the resorption of different classes of plant metabolites. We studied the effect of warming and altered precipitation on the production and resorption of metabolites in Quercus rubra. The combination of warming and drought produced a higher abundance of compounds that can help to mitigate climatic stress by functioning as osmoregulators and antioxidants, including important intermediaries of the tricarboxylic acid cycle, amino acids including proline and citrulline, and polyamines such as putrescene. Resorption efficiencies (RE) of extractable metabolites surprisingly had opposite responses to drought and warming; drought treatments generally increased RE of metabolites compared to ambient and wet treatments, while warming decreased RE. However, RE of total N differed markedly from that of extractable metabolites such as amino acids; for instance, droughted plants resorbed very little N from their leaves; a smaller fraction than plants exposed to the ambient control. In contrast, plants in drought treatment resorbed amino acids more efficiently (> 90%) than those in ambient (65-77%) or wet (42-58%) treatments. Across the climate treatments the RE of elemental N correlated negatively with tissue tannin concentration, indicating that polyphenols produced in leaves under climatic stress could interfere with N resorption. Thus, senesced leaves from drier conditions might have a lower nutritive value to soil heterotrophs during the initial stages of litter decomposition despite a higher elemental N content of these tissues. Our results suggest that N resorption may be controlled not only by plant demand, but also by climatic influences on the production and resorption of plant metabolites. As climate-carbon models incorporate increasingly sophisticated nutrient cycles, these results highlight the need to adequately understand plant physiological responses to climatic variables. This article is protected by copyright. All rights reserved. PMID: 26179236 [PubMed - as supplied by publisher]

Related Articles Environmental metabolomics: Biological markers for metal toxicity. Electrophoresis. 2015 Jul 14; Authors: García-Sevillano MÁ, García-Barrera T, Gómez-Ariza JL Abstract Environmental metabolomics is an emerging field referred to the application of metabolomics to characterize the interactions of living organisms with their environment. In this sense, the importance of monitoring the effects of toxic metals on living organisms has increased as a consequence of natural changes and anthropogenic activities that have led to an increase of toxic metals levels in terrestrial and aquatic ecosystems. For this purpose, the use of metabolomics based on mass spectrometry to study metal toxicity is gaining importance in recent years. Environmental metabolomics can be used to: discover the mode of action (MOA) of toxic metals through controlled laboratory experiments; evaluate toxicity (biological adverse response to a substance), that may be useful in risk assessment; and develop new biomarkers (based in metabolome shifts discovered through controlled laboratory experiments) that may be applied in environmental biomonitoring (environmental realistic scenario). In this review, it is discussed how metabolomics based on mass spectrometry can be applied to study metal toxicity, considering the most important hallmarks related to metabolomic experiments. This article is protected by copyright. All rights reserved. PMID: 26177839 [PubMed - as supplied by publisher]