PubMed

Related Articles Brown adipose tissue harbors a distinct sub-population of regulatory T cells. PLoS One. 2015;10(2):e0118534 Authors: Medrikova D, Sijmonsma TP, Sowodniok K, Richards DM, Delacher M, Sticht C, Gretz N, Schafmeier T, Feuerer M, Herzig S Abstract Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress. PMID: 25714366 [PubMed - indexed for MEDLINE]

Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract. J Ethnopharmacol. 2016 Jan 13; Authors: Maulidiani, Abas F, Khatib A, Perumal V, Suppaiah V, Ismail A, Hamid M, Shaari K, Lajis NH Abstract ETHNOPHARMACOLOGICAL RELEVANCE: 'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach. METHOD: In this study, an obese diabetic (mimic of T2DM condition) animal model was developed using Sprague-Dawley rats fed with a high-fat diet and induced into diabetic condition by the treatment of a low dose of streptozotocin (STZ). The effect of C. asiatica extract on the experimental animals was followed based on the changes observed in the urinary and serum metabolites, measured by (1)H NMR of urine and blood samples collected over the test period. RESULTS: A long-term treatment of obese diabetic rats with CAextract could reverse the glucose and lipid levels, as well as the tricarboxylic acid cycle and amino acid metabolic disorders, back towards normal states. Biochemical analysis also showed an increase of insulin production in diabetic rats upon treatment of CA extract. CONCLUSION: This study has provided evidence that clearly supported the traditional use of CA as a remedy for diabetes. NMR-based metabolomics was successfully applied to show that CA produced both anti-hyperglycemic and anti-hyperlipidemic effects on a rat model. In addition to increasing the insulin secretion, the CA extract also ameliorates the metabolic pathways affected in the induced diabectic rats. This study further revealed the potential usage of CA extract in managing diabetes mellitus and the results of this work may contribute towards the further understanding of the underlying molecular mechanism of this herbal remedy. PMID: 26775274 [PubMed - as supplied by publisher]

Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism. Cell Metab. 2016 Jan 6; Authors: Quaegebeur A, Segura I, Schmieder R, Verdegem D, Decimo I, Bifari F, Dresselaers T, Eelen G, Ghosh D, Davidson SM, Schoors S, Broekaert D, Cruys B, Govaerts K, De Legher C, Bouché A, Schoonjans L, Ramer MS, Hung G, Bossaert G, Cleveland DW, Himmelreich U, Voets T, Lemmens R, Bennett CF, Robberecht W, De Bock K, Dewerchin M, Ghesquière B, Fendt SM, Carmeliet P Abstract The oxygen-sensing prolyl hydroxylase domain proteins (PHDs) regulate cellular metabolism, but their role in neuronal metabolism during stroke is unknown. Here we report that PHD1 deficiency provides neuroprotection in a murine model of permanent brain ischemia. This was not due to an increased collateral vessel network. Instead, PHD1(-/-) neurons were protected against oxygen-nutrient deprivation by reprogramming glucose metabolism. Indeed, PHD1(-/-) neurons enhanced glucose flux through the oxidative pentose phosphate pathway by diverting glucose away from glycolysis. As a result, PHD1(-/-) neurons increased their redox buffering capacity to scavenge oxygen radicals in ischemia. Intracerebroventricular injection of PHD1-antisense oligonucleotides reduced the cerebral infarct size and neurological deficits following stroke. These data identify PHD1 as a regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke. PMID: 26774962 [PubMed - as supplied by publisher]

A metabolomic study of fipronil for the anxiety-like behavior in zebrafish larvae at environmentally relevant levels. Environ Pollut. 2016 Jan 14;211:252-258 Authors: Wang C, Qian Y, Zhang X, Chen F, Zhang Q, Li Z, Zhao M Abstract Field residue of fipronil can interfere with the physiological characters of the domesticated fish; thus, lethal dose test and the general biomarker cannot delineate the low-level situation. Manipulating by video track, we observed an anxiety-like behavior including high speed and abnormal photoperiod accommodation after exposure to fipronil at environmental typical dose in zebrafish larvae. Examining the unbiased metabolomic profiles, we found perturbation in several metabolic pathways, including the increased contents of fatty acids and glycerol and the decreased levels of the glycine, serine, and branched amino acid. We presumed that observed enhanced fatty acid utility was in response to increase energy demands caused by anxiety like behavior. Additionally, the body burden of neurotransmitter such as glycine and l-glutamate may concurrently stimulate the swimming behavior. The insight of this study showed that integral perturbation such as metabolism helps us to further understand the risk to aquatic fish at the environmentally relevant levels. PMID: 26774772 [PubMed - as supplied by publisher]

Selective elimination of the free fatty acid fraction from esterified fatty acids in rat plasma through chemical derivatization and immobilization on amino functionalized silica nano-particles. J Chromatogr A. 2015 Dec 31; Authors: Chen J, Lyu Q, Yang M, Chen Z, He J Abstract A high throughput and low cost approach to separate free fatty acids (FFAs) from phospholipid and acylglycerols (esterified fatty acids, EFAs) has been demonstrated, which may be widely used as a sample preparation method in the metabolomics and lipid research. The optimal conditions for FFAs reacting with N-hydroxysuccinimide (NHS) only need 10min at room temperature to obtain a 93.5% yield of FFAs-NHS ester. The rest 6% FFA transformed into N-cyclohexyl-fatty acid-amide which is stable to methyl esterification adopted for fatty acids analysis. 10min are taken for FFAs-NHS ester to react with amino functionalized silica nanoparticles to immobilize the FFAs. The separation of FFAs from EFAs could be carried out readily by centrifugation. The whole process including derivatization, immobilization, and centrifugation takes less than 40min. Much more accurate fatty acids composition of rat plasma EFAs could be obtained by this approach than the previous reported methods. PMID: 26774120 [PubMed - as supplied by publisher]

Related Articles Comparative UPLC-QTOF-MS-based metabolomics and bioactivities analyses of Garcinia oblongifolia. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 4;1011:179-195 Authors: Li P, AnandhiSenthilkumar H, Wu SB, Liu B, Guo ZY, Fata JE, Kennelly EJ, Long CL Abstract Garcinia oblongifolia Champ. ex Benth. (Clusiaceae) is a well-known medicinal plant from southern China, with edible fruits. However, the phytochemistry and bioactivity of the different plant parts of G. oblongifolia have not been studied extensively. Comparative metabolic profiling and bioactivities of the leaf, branch, and fruit of G. oblongifolia were investigated. A total of 40 compounds such as biflavonoids, xanthones, and benzophenones were identified using UPLC-QTOF-MS and MS(E), including 15 compounds reported for the first time from this species. Heatmap analyses found that benzophenones, xanthones, and biflavonoids were predominately found in branches, with benzophenones present in relatively high concentrations in all three plant parts. Xanthones were found to have limited distribution in fruit while biflavonoids were present at only low levels in leaves. In addition, the cytotoxic (MCF-7 breast cancer cell line) and antioxidant (ABTS and DPPH chemical tests) activities of the crude extracts of G. oblongifolia indicate that the branch extract exhibits greater bioactivity than either the leaf or the fruit extracts. Orthogonal partial least squares discriminate analysis was used to find 12 marker compounds, mainly xanthones, from the branches, including well-known antioxidants and cytotoxic agents. These G. oblongifolia results revealed that the variation in metabolite profiles can be correlated to the differences in bioactivity of the three plant parts investigated. This UPLC-QTOF-MS strategy can be useful to identify bioactive constituents expressed differentially in the various plant parts of a single species. PMID: 26773895 [PubMed - as supplied by publisher]

Related Articles Ornithine is a key mediator in hyperphosphatemia-mediated human umbilical vein endothelial cell apoptosis: Insights gained from metabolomics. Life Sci. 2016 Jan 7; Authors: Zhou R, Kang X, Tang B, Mohan C, Wu T, Peng A, Liu JY Abstract AIMS: Hyperphosphatemia is associated with accelerated vascular endothelial dysfunction in patients with chronic kidney disease (CKD). The purpose of this study is to investigate the molecular mechanisms underlying hyperphosphatemia-caused endothelial dysfunction. MAIN METHODS: The metabolic fingerprinting of human umbilical vein endothelial cells (HUVECs) subjected to hyperphosphatemia was characterized using an integrated metabolomics approach. HUVECs cultured in physiologically simulated hyperphosphatemia with or without phosphonoformic acid, a sodium-dependent phosphate transporter inhibitor (N=6) were collected for metabolomics analysis. Multivariate principle component analysis and partial least squares discriminant analysis were applied to analyze the metabolic data. The key metabolites were confirmed by quantitative analysis using liquid chromatography coupled with tandem mass spectrometer (LC-MS/MS). KEY FINDINGS: 36 metabolites were significantly altered in HUVECs following the challenges of hyperphosphatemia mimic, involving several metabolic pathways (all P<0.05). Among them, ornithine increased significantly in the HUVECs mediated by hyperphosphatemia mimic, and its levels positively correlated with cell apoptosis rate (r=0.674, P=0.002), and several additional metabolites in multiple metabolic pathways. The changes in the levels of ornithine and other several metabolites were supported by subsequent quantitative analyses using LC-MS/MS. Further study demonstrated that the increase in ornithine level may result from the increased expression of arginase 2 in HUVECs, which mediates the hydrolysis of arginine to form ornithine. SIGNIFICANCE: This is the first study demonstrating ornithine a key molecule mediating hyperphosphatemia-induced apoptosis of ECs. Arginase 2 may be a therapeutic target for hyperphosphatemia-associated cardiovascular events. PMID: 26773858 [PubMed - as supplied by publisher]

Related Articles Transgenic barley overexpressing a cytokinin dehydrogenase gene shows greater tolerance to drought stress. N Biotechnol. 2016 Jan 7; Authors: Pospíšilová H, Jiskrová E, Vojta P, Mrízová K, Kokáš F, Čudejková MM, Bergougnoux V, Plíhal O, Klimešová J, Novák O, Dzurová L, Frébort I, Galuszka P Abstract Together with auxins, cytokinins are the main plant morphogens involved in many different physiological processes. Given this knowledge, cytokinin levels can be manipulated by genetic modification in order to improve agronomic parameters of cereals in relation to, for example, morphology, yield, and tolerance to various stresses. The barley (Hordeum vulgare) cultivar Golden Promise was transformed using the cytokinin dehydrogenase 1 gene from Arabidopsis thaliana (AtCKX1) under the control of mild root-specific β-glucosidase promoter from maize. Increased cytokinin degradation activity was observed positively to affect the number and length of lateral roots. The impact on morphology depended upon the recombinant protein's subcellular compartmentation. While assumed cytosolic and vacuolar targeting of AtCKX1 had negligible effect on shoot growth, secretion of AtCKX1 protein to the apoplast had a negative effect on development of the aerial part and yield. Upon the application of severe drought stress, all transgenic genotypes maintained higher water content and showed better growth and yield parameters during revitalization. Higher tolerance to drought stress was most caused by altered root morphology resulting in better dehydration avoidance. PMID: 26773738 [PubMed - as supplied by publisher]

Related Articles (1)H NMR-based metabolomics study on the physiological variations during the rat pregnancy process. Mol Cell Endocrinol. 2016 Jan 7; Authors: Shen G, Li Z, Zhang Y, Wu H, Feng J Abstract In this study, NMR-based metabolomics in combination with multivariate pattern recognition technologies were employed to evaluate the physiological variations in the Wistar rats' plasma that are induced by pregnancy on the gestational days (GDs) 11, 14, 17 and 20. Untargeted metabolomics analysis revealed some possible mechanism of physiological effects for healthy pregnancies and showed a metabolic trajectory during pregnancy process. The levels of 24 metabolites were found to change significantly throughout pregnancy in maternal plasma. These metabolite changes involved in varied kinds of metabolic pathways including synthesis of biological substances, microbial metabolism in diverse environments, protein digestion and absorption, carbohydrate metabolism, digestion and absorption, mineral absorption, and ATP (Adenosine Triphosphate)-binding cassette transporters (ABC transporters). The substantial cores of all the metabolic pathways are promoting fetal growth and development and regulating maternal physiological state. This work showed relevant metabolic pathways perturbation in the maternal plasma due to normal pregnancy and provided the physical basis of time-dependent metabolic trajectory against which disease-related maternal physiological responses may be better understood in future studies. PMID: 26773731 [PubMed - as supplied by publisher]

Related Articles Minimum dominating set-based methods for analyzing biological networks. Methods. 2016 Jan 7; Authors: Nacher JC, Akutsu T Abstract The fast increase of 'multi-omics' data does not only pose a computational challenge for its analysis but also requires novel algorithmic methodologies to identify complex biological patterns and decipher the ultimate roots of human disorders. To that end, the massive integration of omics data with disease phenotypes is offering a new window into the cell functionality. The minimum dominating set (MDS) approach has rapidly emerged as a promising algorithmic method to analyze complex biological networks integrated with human disorders, which can be composed of a variety of omics data, from proteomics and transcriptomics to metabolomics. Here we review the main theoretical foundations of the methodology and the key algorithms, and examine the recent applications in which biological systems are analyzed by using the MDS approach. PMID: 26773457 [PubMed - as supplied by publisher]

Related Articles Choline, Its Potential Role in Nonalcoholic Fatty Liver Disease, and the Case for Human and Bacterial Genes. Adv Nutr. 2016 Jan;7(1):5-13 Authors: Sherriff JL, O'Sullivan TA, Properzi C, Oddo JL, Adams LA Abstract Our understanding of the impact of poor hepatic choline/phosphatidylcholine availability in promoting the steatosis characteristic of human nonalcoholic fatty liver disease (NAFLD) has recently advanced and possibly relates to phosphatidylcholine/phosphatidylethanolamine concentrations in various, membranes as well as cholesterol dysregulation. A role for choline/phosphatidylcholine availability in the progression of NAFLD to liver injury and serious hepatic consequences in some individuals requires further elucidation. There are many reasons for poor choline/phosphatidylcholine availability in the liver, including low intake, estrogen status, and genetic polymorphisms affecting, in particular, the pathway for hepatic de novo phosphatidylcholine synthesis. In addition to free choline, phosphatidylcholine has been identified as a substrate for trimethylamine production by certain intestinal bacteria, thereby reducing host choline bioavailability and providing an additional link to the increased risk of cardiovascular disease faced by those with NAFLD. Thus human choline requirements are highly individualized and biomarkers of choline status derived from metabolomics studies are required to predict those at risk of NAFLD induced by choline deficiency and to provide a basis for human intervention trials. PMID: 26773011 [PubMed - as supplied by publisher]

Related Articles An acetyl-L-carnitine switch on mitochondrial dysfunction and rescue in the metabolomics study on aluminum oxide nanoparticles. Part Fibre Toxicol. 2016;13(1):4 Authors: Li X, Zhang C, Zhang X, Wang S, Meng Q, Wu S, Yang H, Xia Y, Chen R Abstract BACKGROUND: Due to the wide application of engineered aluminum oxide nanoparticles and increased aluminum containing particulate matter suspending in air, exposure of human to nano-scale aluminum oxide nanoparticles (Al2O3 NPs) is becoming inevitable. METHODS: In the present study, RNA microarray coupled with metabolomics analysis were used to uncover mechanisms underlying cellular responses to Al2O3 NPs and imply the potential rescue. RESULTS: We found that Al2O3 NPs significantly triggered down-regulation of mitochondria-related genes located in complex I, IV and V, which were involved in oxidative phosphorylation and neural degeneration pathways, in human bronchial epithelial (HBE) cells. Subsequent cell- and animal- based assays confirmed that Al2O3 NPs caused mitochondria-dependent apoptosis and oxidative stress either in vitro or in vivo, which were consistent with the trends of gene regulation. To rescue the Al2O3 NPs induced mitochondria dysfunction, disruption of small molecular metabolites of HBE were profiled using metabolomics analysis, which facilitates identification of potential antagonizer or supplement against nanoparticle-involved damages. Supplementation of an antioxidant, acetyl-L-carnitine, completely or partially restored the Al2O3 NPs modulated gene expression levels in mitochondrial complex I, IV and V. It further reduced apoptosis and oxidative damages in both Al2O3 NPs treated HBE cells and animal lung tissues. CONCLUSION: Thus, our results demonstrate the potential mechanism of respiratory system damages induced by Al2O3 NPs. Meanwhile, based on the metabolomics profiling, application of acetyl-L-carnitine is suggested to ameliorate mitochondria dysfunction associated with Al2O3 NPs. PMID: 26772537 [PubMed - as supplied by publisher]

Related Articles Metabolomic Technologies for Improving the Quality of Food: Practice and Promise. Annu Rev Food Sci Technol. 2016 Jan 11; Authors: Johanningsmeier SD, Harris GK, Klevorn CM Abstract It is now well documented that the diet has a significant impact on human health and well-being. However, the complete set of small molecule metabolites present in foods that make up the human diet and the role of food production systems in altering this food metabolome are still largely unknown. Metabolomic platforms that rely on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analytical technologies are being employed to study the impact of agricultural practices, processing, and storage on the global chemical composition of food; to identify novel bioactive compounds; and for authentication and region-of-origin classifications. This review provides an overview of the current terminology, analytical methods, and compounds associated with metabolomic studies, and provides insight into the application of metabolomics to generate new knowledge that enables us to produce, preserve, and distribute high-quality foods for health promotion. Expected final online publication date for the Annual Review of Food Science and Technology Volume 7 is February 28, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 26772413 [PubMed - as supplied by publisher]

Related Articles Metabolomic biomarkers for personalised glucose lowering drugs treatment in type 2 diabetes. Metabolomics. 2016;12:27 Authors: den Ouden H, Pellis L, Rutten GE, Geerars-van Vonderen IK, Rubingh CM, van Ommen B, van Erk MJ, Beulens JW Abstract We aimed to identify metabolites to predict patients' response to glucose lowering treatment during the first 5 years after detection of type 2 diabetes. Metabolites were measured by GC-MS in baseline samples from 346 screen-detected type 2 diabetes patients in the ADDITION-NL study. The response to treatment with metformin and/or sulphonylurea (SU) was analysed to identify metabolites predictive of 5 year HbA1c change by multiple regression analysis. Baseline glucose and 1,5 anhydro-glucitol were associated with HbA1c decrease in all medication groups. In patients on SU no other metabolite was associated with HbA1c decrease. A larger set of metabolites was associated with HbA1c change in the metformin and the combination therapy (metformin + SU) groups. These metabolites included metabolites related to liver metabolism, such as 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, 2-hydroxypiperidine and 4-oxoproline). Metabolites involved in oxidative stress and insulin resistance were higher when the HbA1c decrease was larger in the metformin/sulphonylurea group. The associations between baseline metabolites and responsiveness to medication are in line with its mode of action. If these results could be replicated in other populations, the most promising predictive candidates might be tested to assess whether they could enhance personalised treatment. PMID: 26770180 [PubMed - as supplied by publisher]

Related Articles Extending metabolome coverage for untargeted metabolite profiling of adherent cultured hepatic cells. Anal Bioanal Chem. 2016 Jan 14; Authors: García-Cañaveras JC, López S, Castell JV, Donato MT, Lahoz A Abstract MS-based metabolite profiling of adherent mammalian cells comprises several challenging steps such as metabolism quenching, cell detachment, cell disruption, metabolome extraction, and metabolite measurement. In LC-MS, the final metabolome coverage is strongly determined by the separation technique and the MS conditions used. Human liver-derived cell line HepG2 was chosen as adherent mammalian cell model to evaluate the performance of several commonly used procedures in both sample processing and LC-MS analysis. In a first phase, metabolite extraction and sample analysis were optimized in a combined manner. To this end, the extraction abilities of five different solvents (or combinations) were assessed by comparing the number and the levels of the metabolites comprised in each extract. Three different chromatographic methods were selected for metabolites separation. A HILIC-based method which was set to specifically separate polar metabolites and two RP-based methods focused on lipidome and wide-ranging metabolite detection, respectively. With regard to metabolite measurement, a Q-ToF instrument operating in both ESI (+) and ESI (-) was used for unbiased extract analysis. Once metabolite extraction and analysis conditions were set up, the influence of cell harvesting on metabolome coverage was also evaluated. Therefore, different protocols for cell detachment (trypsinization or scraping) and metabolism quenching were compared. This study confirmed the inconvenience of trypsinization as a harvesting technique, and the importance of using complementary extraction solvents to extend metabolome coverage, minimizing interferences and maximizing detection, thanks to the use of dedicated analytical conditions through the combination of HILIC and RP separations. The proposed workflow allowed the detection of over 300 identified metabolites from highly polar compounds to a wide range of lipids. Graphical abstract A novel analytical workflow for the LC-MS-based metabolomic analysis of adherent cultured hepatic cells was developed. Three key steps were evaluated: a) cell harvesting, which includes cell detachment and metabolism quenching; b) metabolite extraction; and c) LC-MS analysis, assessing the use of RP and HILIC chromatographies. The final protocol allowed us to extend the metabolome coverage and enabled the detection of a wide range of metabolites from highly polar compounds to a wide range of lipids. PMID: 26769129 [PubMed - as supplied by publisher]

Related Articles A metabonomic analysis reveals novel regulatory mechanism of Huangqi injection on leucopenia mice. Immunopharmacol Immunotoxicol. 2016 Jan 15;:1-11 Authors: Qu T, Li Z, Zhao S, Li A, Qin X Abstract CONTEXT: Huangqi injection (HQI), extracted from Astragali Radix, which has capability on treating the leucopenia. However, the potential metabolic mechanism is poorly understood. OBJECTIVE: To investigate the effect of HQI on cyclophosphamide (Cy)-induced leucopenia in mice, the nuclear magnetic resonance (NMR)-based metabolomic profiling technique coupled with multivariate statistical analysis was applied. MATERIALS AND METHODS: NMR analysis was used to identify the various compounds of HQI, and high-performance liquid chromatography was applied to determine the contents of major compounds. A experimental mice model of leucopenia induced by Cy and NMR-based metabolomic approach was used to evaluate the pharmacological effect of HQI and to investigate its probable acting mechanism on leucopenia. RESULTS: HQI increased body weight and elevated the white blood cell (WBC), monocytes (MO), neutrophils (NE), and lymphocyte (LY) levels of Cy-treated mice. In addition, the levels of most perturbed endogenous metabolites could be reversed after HQI treatment. Correlations between WBC, MO, NE, LY, and altered metabolite profiles in spleen were greater than that in serum, and the correlation in MO was more evident than those for WBC, NE, and LY. DISCUSSION AND CONCLUSION: HQI showed obvious efficacy on the mice model of leucopenia. And the drug action of HQI on leucopenia was probably related with regulating metabolic pathways of energy metabolism, amino acids metabolism, oxidative stress, and choline metabolism. However, various compounds were present in the HQI, and the bioactive compounds responsible for the drug actions should be further investigated. PMID: 26769054 [PubMed - as supplied by publisher]

Related Articles Biomarkers in localized prostate cancer. Future Oncol. 2016 Jan 15; Authors: Ferro M, Buonerba C, Terracciano D, Lucarelli G, Cosimato V, Bottero D, Deliu VM, Ditonno P, Perdonà S, Autorino R, Coman I, Placido S, Lorenzo GD, Cobelli O Abstract Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID: 26768791 [PubMed - as supplied by publisher]

Related Articles [Effect of Acanthopanax senticosus Polysaccharides on Cardiac Endogenous Metabolism in Rats Based on Metabolomics]. Zhong Yao Cai. 2015 May;38(5):1004-8 Authors: Lu F, Yang XD, Jing YE, Zhang N, Liu SM Abstract OBJECTIVE: Using metabolomics method to study the influence of Acanthopanax senticosus polysaccharides on cardiac endogenous metabolism in rats, in order to find potential biomarkers and analyze the metabolic pathways which can explore the pharmacological effects and mechanisms of action. METHODS: 20 SD rats were randomly divided into two groups, the blank and Acanthopanax senticosus polysaccharides treatment groups, which were treated with saline and Acanthopanax senticosus polysaccharide for 20 days. On the 21th day,heart tissue were collected and each sample extract was analyzed by UPLC-Q-TOF/MS. RESULTS: 20 potential biomarkers and 6 major metabolic pathways related to cardiovascular and cerebrovascular diseases were identified. CONCLUSION: Acanthopanax senticosus polysaccharides has a certain pharmacological effects on cardio-cerebro vascular diseases, cancer and other diseases. Its mechanism may be related to the metabolic process of amino acids, fatty acid and folate. PMID: 26767296 [PubMed - in process]

Related Articles Genomic and experimental evidence for multiple metabolic functions in the RidA/YjgF/YER057c/UK114 (Rid) protein family. BMC Genomics. 2015;16:382 Authors: Niehaus TD, Gerdes S, Hodge-Hanson K, Zhukov A, Cooper AJ, ElBadawi-Sidhu M, Fiehn O, Downs DM, Hanson AD Abstract BACKGROUND: It is now recognized that enzymatic or chemical side-reactions can convert normal metabolites to useless or toxic ones and that a suite of enzymes exists to mitigate such metabolite damage. Examples are the reactive imine/enamine intermediates produced by threonine dehydratase, which damage the pyridoxal 5'-phosphate cofactor of various enzymes causing inactivation. This damage is pre-empted by RidA proteins, which hydrolyze the imines before they do harm. RidA proteins belong to the YjgF/YER057c/UK114 family (here renamed the Rid family). Most other members of this diverse and ubiquitous family lack defined functions. RESULTS: Phylogenetic analysis divided the Rid family into a widely distributed, apparently archetypal RidA subfamily and seven other subfamilies (Rid1 to Rid7) that are largely confined to bacteria and often co-occur in the same organism with RidA and each other. The Rid1 to Rid3 subfamilies, but not the Rid4 to Rid7 subfamilies, have a conserved arginine residue that, in RidA proteins, is essential for imine-hydrolyzing activity. Analysis of the chromosomal context of bacterial RidA genes revealed clustering with genes for threonine dehydratase and other pyridoxal 5'-phosphate-dependent enzymes, which fits with the known RidA imine hydrolase activity. Clustering was also evident between Rid family genes and genes specifying FAD-dependent amine oxidases or enzymes of carbamoyl phosphate metabolism. Biochemical assays showed that Salmonella enterica RidA and Rid2, but not Rid7, can hydrolyze imines generated by amino acid oxidase. Genetic tests indicated that carbamoyl phosphate overproduction is toxic to S. enterica cells lacking RidA, and metabolomic profiling of Rid knockout strains showed ten-fold accumulation of the carbamoyl phosphate-related metabolite dihydroorotate. CONCLUSIONS: Like the archetypal RidA subfamily, the Rid2, and probably the Rid1 and Rid3 subfamilies, have imine-hydrolyzing activity and can pre-empt damage from imines formed by amine oxidases as well as by pyridoxal 5'-phosphate enzymes. The RidA subfamily has an additional damage pre-emption role in carbamoyl phosphate metabolism that has yet to be biochemically defined. Finally, the Rid4 to Rid7 subfamilies appear not to hydrolyze imines and thus remain mysterious. PMID: 25975565 [PubMed - indexed for MEDLINE]

Related Articles Discovery of substrate cycles in large scale metabolic networks using hierarchical modularity. BMC Syst Biol. 2015;9:5 Authors: Sridharan GV, Ullah E, Hassoun S, Lee K Abstract BACKGROUND: A substrate cycle is a set of metabolic reactions, arranged in a loop, which does not result in net consumption or production of the metabolites. The cycle operates by transforming a cofactor, e.g. oxidizing a reducing equivalent. Substrate cycles have been found experimentally in many parts of metabolism; however, their physiological roles remain unclear. As genome-scale metabolic models become increasingly available, there is now the opportunity to comprehensively catalogue substrate cycles, and gain additional insight into this potentially important motif of metabolic networks. RESULTS: We present a method to identify substrate cycles in the context of metabolic modules, which facilitates functional analysis. This method utilizes elementary flux mode (EFM) analysis to find potential substrate cycles in the form of cyclical EFMs, and combines this analysis with network partition based on retroactive (cyclical) interactions between reactions. In addition to providing functional context, partitioning the network into modules allowed exhaustive EFM calculations on smaller, tractable subnetworks that are enriched in metabolic cycles. Applied to a large-scale model of human liver metabolism (HepatoNet1), our method found not only well-known substrate cycles involving ATP hydrolysis, but also potentially novel substrate cycles involving the transformation of other cofactors. A key characteristic of the substrate cycles identified in this study is that the lengths are relatively short (2-13 reactions), comparable to many experimentally observed substrate cycles. CONCLUSIONS: EFM computation for large scale networks remains computationally intractable for exhaustive substrate cycle enumeration. Our algorithm utilizes a 'divide and conquer' strategy where EFM analysis is performed on systematically identified network modules that are designed to be enriched in cyclical interactions. We find that several substrate cycles uncovered using our approach are not identified when the network is partitioned in a more generic manner based solely on connectivity rather than cycles, demonstrating the value of targeting motif searches to sub-networks replete with a topological feature that resembles the desired motif itself. PMID: 25884368 [PubMed - indexed for MEDLINE]