PubMed

GTPase domain driven dimerization of SEPT7 is dispensable for the critical role of septins in fibroblast cytokinesis. Sci Rep. 2016;6:20007 Authors: Abbey M, Hakim C, Anand R, Lafera J, Schambach A, Kispert A, Taft MH, Kaever V, Kotlyarov A, Gaestel M, Menon MB Abstract Septin 7 (SEPT7) has been described to be essential for successful completion of cytokinesis in mouse fibroblasts, and Sept7-deficiency in fibroblasts constitutively results in multinucleated cells which stop proliferation. Using Sept7(flox/flox)fibroblasts we generated a cellular system, where the cytokinetic defects of Cre-mediated deletion of the Sept7 gene can be rescued by ectopically expressed doxycycline-inducible wild type SEPT7. Using this system, we analyzed the ability of SEPT7-mutants with alterations in their GTPase domain-dependent dimerization to prevent multinucleation and rescue proliferation. Although biochemical analysis of the mutants demonstrates differences in homo- and/or hetero-polymerization, in GTP-binding and/or GTPase activities, all analyzed mutants were able to rescue the cytokinesis phenotype of Sept7(flox/flox)fibroblasts associated with Cre-mediated deletion of endogenous Sept7. These findings indicate that the ability of septins to assemble into well-defined SEPT7-dimerization dependent native filaments is dispensable for cytokinesis in fibroblasts and opens the way to search for other mechanisms of the involvement of SEPT7 in cytokinesis. PMID: 26818767 [PubMed - in process]

Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study. BMC Med. 2016;14(1):13 Authors: Kühn T, Floegel A, Sookthai D, Johnson T, Rolle-Kampczyk U, Otto W, von Bergen M, Boeing H, Kaaks R Abstract BACKGROUND: First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk. METHODS: Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835 incident cancer cases. RESULTS: The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis. CONCLUSION: Changes in blood lipid composition precede the diagnosis of common malignancies by several years. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis. PMID: 26817443 [PubMed - in process]

Related Articles Prediction of Anti-inflammatory Plants and Discovery of Their Biomarkers by Machine Learning Algorithms and Metabolomic Studies. Planta Med. 2015 Apr;81(6):450-8 Authors: Chagas-Paula DA, Oliveira TB, Zhang T, Edrada-Ebel R, Da Costa FB Abstract Nonsteroidal anti-inflammatory drugs are the most used anti-inflammatory medicines in the world. Side effects still occur, however, and some inflammatory pathologies lack efficient treatment. Cyclooxygenase and lipoxygenase pathways are of utmost importance in inflammatory processes; therefore, novel inhibitors are currently needed for both of them. Dual inhibitors of cyclooxygenase-1 and 5-lipoxygenase are anti-inflammatory drugs with high efficacy and low side effects. In this work, 57 leaf extracts (EtOH-H2O 7 : 3, v/v) from Asteraceae species with in vitro dual inhibition of cyclooxygenase-1 and 5-lipoxygenase were analyzed by high-performance liquid chromatography-high-resolution-ORBITRAP-mass spectrometry analysis and subjected to in silico studies using machine learning algorithms. The data from all samples were processed by employing differential expression analysis software coupled to the Dictionary of Natural Products for dereplication studies. The 6052 chromatographic peaks (ESI positive and negative modes) of the extracts were selected by a genetic algorithm according to their respective anti-inflammatory properties; after this procedure, 1241 of them remained. A study using a decision tree classifier was carried out, and 11 compounds were determined to be biomarkers due to their anti-inflammatory potential. Finally, a model to predict new biologically active extracts from Asteraceae species using liquid chromatography-mass spectrometry information with no prior knowledge of their biological data was built using a multilayer perceptron (artificial neural networks) with the back-propagation algorithm using the biomarker data. As a result, a new and robust artificial neural network model for predicting the anti-inflammatory activity of natural compounds was obtained, resulting in a high percentage of correct predictions (81 %), high precision (100 %) for dual inhibition, and low error values (mean absolute error = 0.3), as also shown in the validation test. Thus, the biomarkers of the Asteraceae extracts were statistically correlated with their anti-inflammatory activities and can therefore be useful to predict new anti-inflammatory extracts and their anti-inflammatory compounds using only liquid chromatography-mass spectrometry data. PMID: 25615275 [PubMed - indexed for MEDLINE]

Erratum to: Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry. Ann Pediatr Endocrinol Metab. 2015 Dec;20(4):238 Authors: Yoon HR Abstract [This corrects the article on p. 119 in vol. 20, PMID: 26512346.]. PMID: 26817013 [PubMed - as supplied by publisher]

Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity. Am J Physiol Endocrinol Metab. 2016 Jan 26;:ajpendo.00492.2015 Authors: Patterson RE, Kalavalapalli S, Williams CM, Nautiyal M, Mathew JT, Martinez J, Reinhard MK, McDougall DJ, Rocca JR, Yost RA, Cusi K, Garrett TJ, Sunny NE Abstract The hepatic tri-carboxylic acid (TCA) cycle is central to integrating macronutrient metabolism, and is closely coupled to cellular respiration, free radical generation and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through hepatic TCA cycle. Mice (C57/BL6) were fed a high trans-fat high fructose diet (TFD) for 8-weeks to induce simple steatosis and NASH by 24-weeks. In vivo fasting hepatic mitochondrial fluxes were determined by (13)C-nuclear magnetic resonance (NMR) based isotopomer analysis. Hepatic metabolic intermediates were quantified utilizing mass spectrometry based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism as TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a 2-fold induction (p < 0.05) of mitochondrial fluxes (µmoles/ min) through the TCA cycle (2.6 ±0.5 vs. 5.4 ±0.6), anaplerosis (9.1 ±1.2 vs. 16.9 ±2.2) and pyruvate cycling (4.9 ±1.0 vs. 11.1 ±1.9), compared to their age matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis, and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer) and long chain acylcarnitines suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver, and could hasten inflammation and the metabolic transition to NASH. PMID: 26814015 [PubMed - as supplied by publisher]

Weight loss predictability by plasma metabolic signatures in adults with obesity and morbid obesity of the DiOGenes study. Obesity (Silver Spring). 2016 Feb;24(2):379-88 Authors: Stroeve JH, Saccenti E, Bouwman J, Dane A, Strassburg K, Vervoort J, Hankemeier T, Astrup A, Smilde AK, van Ommen B, Saris WH Abstract OBJECTIVE: Aim is to predict successful weight loss by metabolic signatures at baseline and to identify which differences in metabolic status may underlie variations in weight loss success. METHODS: In DiOGenes, a randomized, controlled trial, weight loss was induced using a low-calorie diet (800 kcal) for 8 weeks. Men (N = 236) and women (N = 431) as well as groups with overweight/obesity and morbid obesity were studied separately. The relation between the metabolic status before weight loss and weight loss was assessed by stepwise regression on multiple data sets, including anthropometric parameters, NMR-based plasma metabolites, and LC-MS-based plasma lipid species. RESULTS: Maximally, 57% of the variation in weight loss success can be predicted by baseline parameters. The most powerful predictive models were obtained in subjects with morbid obesity. In these models, the metabolites most predictive for weight loss were acetoacetate, triacylglycerols, phosphatidylcholines, specific amino acids, and creatine and creatinine. This metabolic profile suggests that high energy metabolism activity results in higher amounts of weight loss. CONCLUSIONS: Possible predictive (pre-diet) markers were found for amount of weight loss for specific subgroups. PMID: 26813527 [PubMed - in process]

Advancing sports and exercise genomics: moving from hypothesis-driven single study approaches to large multi-omics collaborative science. Physiol Genomics. 2016 Jan 26;:physiolgenomics.00009.2016 Authors: Tanaka M, Wang G, Pitsiladis YP Abstract The primary use of the traditional candidate gene approach over the past decades in sports genetics has had limited success in identifying genes associated with elite athletic performance. Advances in high-throughput technologies now permit the application of "omics" (e.g. genomics, transcriptomics, metabolomics, proteomics and epigenomics) approaches to examine the global features of a cell, tissue or organism. "Omics" approaches are being applied with some success to a wide range of pertinent biomedical problems such as cancer diagnosis but also in sports science and sports medicine such as for the identification of biomarkers of trainability or blood doping. There is good evidence to suggest that a combined "omics" solution will greatly facilitate discovery of the genetic influences on sporting performance, training response, injury predisposition and other potential determinants of successful human performance. In this regard, large-scale, collaborative efforts involving well-phenotyped cohorts will be essential for major progress to be made. A recent consensus emerged among 15 research groups active in the field of sports genetics to unite their efforts under one new collaborative initiative named the Athlome Project Consortium. The primary aim of the Athlome Project is to combine resources from individual studies and consortia worldwide to collectively study the genotype and phenotype data available on elite athletes, the adaptation to exercise training (in both human and animal models) and the determinants of exercise-related musculoskeletal injuries. This editorial summarizes the challenges and opportunities facing the Athlome Project Consortium and the field of sports and exercise genomics in general. PMID: 26812985 [PubMed - as supplied by publisher]

Related Articles Total Synthesis of Four Stereoisomers of (4Z,7Z,10Z,12E,16Z,18E)-14,20-Dihydroxy-4,7,10,12,16,18-docosahexaenoic Acid and Their Anti-inflammatory Activities. J Org Chem. 2015 Aug 7;80(15):7713-26 Authors: Goto T, Urabe D, Masuda K, Isobe Y, Arita M, Inoue M Abstract A novel anti-inflammatory lipid mediator, (4Z,7Z,10Z,12E,14S,16Z,18E,20R)-14,20-dihydroxy-4,7,10,12,16,18-docosahexaenoic acid (1aa), and its three C14,C20 stereoisomers (1ab,ba,bb) were synthesized in a convergent fashion. The carbon backbone of the target compounds was assembled from seven simple fragments by employing two Sonogashira coupling and three SN2 alkynylation reactions. The thus constructed four internal alkynes were chemoselectively reduced to the corresponding (Z)-alkenes by applying a newly developed stepwise protocol: (i) hydrogenation of the three alkynes using Lindlar catalyst and (ii) formation of the dicobalt hexacarbonyl complex from the remaining alkyne and subsequent reductive decomplexation. The synthetic preparation of the stereochemically defined four isomers 1aa,ab,ba,bb permitted determination of the absolute structure of the isolated natural product to be 1aa. Biological testing of the four synthetic 14,20-dihydroxydocosahexaenoic acids disclosed similar anti-inflammatory activities of the non-natural isomers (1ab,ba,bb) and the natural form (1aa). PMID: 26172872 [PubMed - indexed for MEDLINE]

Related Articles Physico-chemical and metabolomic characterization of KAMUT® Khorasan and durum wheat fermented dough. Food Chem. 2015 Nov 15;187:451-9 Authors: Balestra F, Laghi L, Taneyo Saa D, Gianotti A, Rocculi P, Pinnavaia G Abstract Investigations were made in order to evaluate the influence of the flour type, chemical acidification and fermentation on characteristics of doughs obtained with durum wheat and KAMUT® Khorasan flour. Doughs were observed immediately after mixing, 90 and 360 min of leavening at 30 °C. Fundamental rheology, yeasts heat production by isothermal microcalorimetry and the interaction between water and biopolymers by means of time domain nuclear magnetic resonance were evaluated. In addition aromatic metabolite development was followed by means of the combined application of gas-chromatography and electronic nose. KAMUT® Khorasan flour was found to be more suitable than durum wheat for the fermentation processes tested, especially at acidic conditions, as shown by the increase of the volume and the metabolic heat production by yeast. In acidified dough the pattern of volatile metabolites allowed a clear distinction between the types of dough. Moreover the water/starch proton pool was characterized by higher T2 values in the KAMUT® Khorasan samples. PMID: 25977050 [PubMed - indexed for MEDLINE]

Related Articles Fungal artificial chromosomes for mining of the fungal secondary metabolome. BMC Genomics. 2015;16:343 Authors: Bok JW, Ye R, Clevenger KD, Mead D, Wagner M, Krerowicz A, Albright JC, Goering AW, Thomas PM, Kelleher NL, Keller NP, Wu CC Abstract BACKGROUND: With thousands of fungal genomes being sequenced, each genome containing up to 70 secondary metabolite (SM) clusters 30-80 kb in size, breakthrough techniques are needed to characterize this SM wealth. RESULTS: Here we describe a novel system-level methodology for unbiased cloning of intact large SM clusters from a single fungal genome for one-step transformation and expression in a model host. All 56 intact SM clusters from Aspergillus terreus were individually captured in self-replicating fungal artificial chromosomes (FACs) containing both the E. coli F replicon and an Aspergillus autonomously replicating sequence (AMA1). Candidate FACs were successfully shuttled between E. coli and the heterologous expression host A. nidulans. As proof-of-concept, an A. nidulans FAC strain was characterized in a novel liquid chromatography-high resolution mass spectrometry (LC-HRMS) and data analysis pipeline, leading to the discovery of the A. terreus astechrome biosynthetic machinery. CONCLUSION: The method we present can be used to capture the entire set of intact SM gene clusters and/or pathways from fungal species for heterologous expression in A. nidulans and natural product discovery. PMID: 25925221 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress. J Exp Bot. 2015 Apr;66(7):1801-16 Authors: Serra AA, Couée I, Renault D, Gouesbet G, Sulmon C Abstract Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing. PMID: 25618145 [PubMed - indexed for MEDLINE]

19 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 2016/01/27PubMed 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.

Using a proteometabolomic approach to investigate the role of Dufour's gland in pheromone biosynthesis in the social wasp Polybia paulista. J Proteomics. 2016 Jan 22; Authors: Esteves FG, Santos-Pinto JR, Saidemberg DM, Palma MS Abstract Dufour's gland is associated with the venom apparatuses of social wasps and bees. This location and its evolutionary adaptations indicate that it could be involved in the production of alarm pheromones in the social wasp P. paulista. To investigate this hypothesis, the volatile composition of this gland was analyzed and compared to that in the venom. Eighteen compounds were identified as secreted by Dufour's gland, and 16 of these compounds were also identified in the venom, suggesting that the compounds produced by the gland are secreted and mixed with venom in the venom reservoir of this wasp. These compounds were subjected to a field bioassay to investigate their potential action as alarm pheromones. Alcohols and aldehydes elicited the alert behavior in workers, luring them outside the nest, whereas acids attracted the workers in the direction of the source; fatty acid methyl esters elicited aggression. These results suggest that Dufour's gland produces alarm pheromones. To corroborate this hypothesis the proteomic complement of this gland was assigned using a shot-gun strategy; 59 proteins were identified, and the results indicate specialization of Dufour's gland for the metabolism of fatty acids (elongation, esterification unsaturation, reduction, and decarboxylation) in the biosynthesis of alarm pheromones. BIOLOGICAL SIGNIFICANCE: The present knowledge about the role of Dufour's gland among aculeate Hymenoptera insects suggests that it may have many different roles related to the biosynthesis and secretion of chemical markers for different biological functions, though none are related to the elicitation of alarm behaviors for coordinating a mass attack of the colony against intruders. The present study combined the analysis of secreted volatile compounds (as metabolites) with proteome assignments and a field bioassay with synthetic compounds to clearly demonstrate that Dufour's gland does in fact biosynthesize alarm pheromones in social wasps. This strategy may be reproduced in other investigations related to pheromone production in other insects. PMID: 26808590 [PubMed - as supplied by publisher]

UHPLC/Q-TOFMS-based plasma metabolomics of polycystic ovary syndrome patients with and without insulin resistance. J Pharm Biomed Anal. 2016 Jan 15;121:141-150 Authors: Chen YX, Zhang XJ, Huang J, Zhou SJ, Liu F, Jiang LL, Chen M, Jian-Bo W, Yang DZ Abstract Polycystic ovary syndrome (PCOS), characterized with menstrual irregularities, hyperandrogenism and ovulatory abnormalities, is usually companied with insulin resistance (IR) and accounts for one of the most prevalent reproductive dysfunction of premenopausal women. Despite accumulating investigations, diagnostic standards of this pathological condition remain obscure. The aim of present study is to characterize the plasma metabolic characteristics of PCOS patients with and without IR, and subsequently identify the potential biomarkers for the diagnosis of PCOS and its IR complication. A total of 59 plasma samples from eligible healthy controls (CON, n=19), PCOS patients without IR (non-IR PCOS, n=19) and PCOS patients with IR (IR PCOS, n=21) were profiled by an ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOFMS) followed by multivariate statistical analysis. Compared to the healthy controls, significant decrease in the levels of phosphocholines (PCs) and lyso PC (18:2), and increase in trilauric glyceride level were observed in the plasma of IR PCOS. Meanwhile, the significant increase in the levels of saturated fatty acids (palmitic acid and stearic acid) and decanoylcarnitine, and decrease in PC (36:2) and PS (36:0) were found in non-IR PCOS patients. Trilauric glyceride and decanoylcarnitine were identified as the potential biomarkers with the highest sensitivity and specificity for the diagnosis of PCOS patients with and without IR, respectively. Furthermore, based on these alterations of metabolites, MetPA network pathway analysis suggested a profound involvement of the abnormalities of glycerophospholipid, glycerolipid and fatty acid metabolisms in the pathogenesis of PCOS and IR complications. Collectively, LC-MS-based metabolomics provides a promising strategy for complementary diagnosis of PCOS and its IR complication and offers a new insight to understand their pathogenesis mechanisms. PMID: 26808063 [PubMed - as supplied by publisher]

UPLC-QTOFMS based metabolomics followed by stepwise partial least square-discriminant analysis (PLS-DA) explore the possible relation between the variations in secondary metabolites and the phylogenetic divergences of the genus Panax. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 6;1012-1013:61-68 Authors: Nguyen HT, Lee DK, Lee WJ, Lee G, Yoon SJ, Shin BK, Nguyen MD, Park JH, Lee J, Kwon SW Abstract Phylogenetic and metabolomic approaches have long been employed to study evolutionary relationships among plants. Nonetheless, few studies have examined the difference in metabolites within a clade and between clades of the phylogenetic tree. We attempted to relate phylogenetic studies to metabolomics using stepwise partial least squares-discriminant analysis (PLS-DA) for the genus Panax. Samples were analyzed by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOFMS) to obtain metabolite profiles. Initially, conventional principal component analysis was subsequently applied to the metabolomic data to show the limitations in relating the expression of metabolites to divisions in the phylogenetic tree. Thereafter, we introduced stepwise PLS-DA with optimized scaling methods, which were properly applied according to the branches of the phylogenetic tree of the four species. Our approach highlighted metabolites of interest by elucidating the directions and degrees of metabolic alterations in each clade of the phylogenetic tree. The results revealed the relationship between metabolic changes in the genus Panax and its species' evolutionary adaptations to different climates. We believe our method will be useful to help understand the metabolite-evolution relationship. PMID: 26807706 [PubMed - as supplied by publisher]

Metabolomics of chronic obstructive pulmonary disease and obstructive sleep apnea syndrome: response to Maniscalco and Motta. Metabolomics. 2016;12:33 Authors: Mlynarz P, Deja S, Stanimirova I, Zabek A, Barg W, Jankowska R PMID: 26807080 [PubMed - as supplied by publisher]

Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of Paeoniflorin Against ANIT Induced Cholestasis. Phytother Res. 2016 Jan 25; Authors: Chen Z, Zhu Y, Zhao Y, Ma X, Niu M, Wang J, Su H, Wang R, Li J, Liu L, Wei Z, Zhao Q, Chen H, Xiao X Abstract Cholestasis is a leading cause of hepatic accumulation of bile acids resulting in liver injury, fibrosis, and liver failure. Paeoniflorin displays bright prospects in liver protective effect. However, its molecular mechanism has not been well-explored. This study was designed to assess the effects and possible mechanisms of paeoniflorin against alpha-naphthylisothiocyanate-induced liver injury. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight combined with principle component analysis and partial least squares discriminant analysis were integrated to obtain differentiating metabolites for the pathways and clarify mechanisms of disease. The results indicated that paeoniflorin could remarkably downregulate serum biochemical indexes and alleviate the histological damage of liver tissue. Different expression of 14 metabolites demonstrated that paeoniflorin mainly regulated the dysfunctions of glycerophospholipid metabolism and primary bile acid biosynthesis. Moreover, several pathways such as arginine and proline metabolism, ether lipid metabolism, and arachidonic acid metabolism were also related to the efficacy. In conclusion, paeoniflorin has indicated favorable pharmacological effect on serum biochemical indexes and pathological observation on cholestatic model. And metabolomics is a promising approach to unraveling hepatoprotective effects by partially regulating the perturbed pathways, which provide insights into mechanisms of cholestasis. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 26806614 [PubMed - as supplied by publisher]

Metabolomics study on the effects of Buchang Naoxintong capsules for treating cerebral ischemia in rats using UPLC-Q/TOF-MS. J Ethnopharmacol. 2016 Jan 19; Authors: Liu M, Liu X, Wang H, Xiao H, Jing F, Tang L, Li D, Zhang Y, Wu H, Yang H Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Buchang Naoxintong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. However, the therapeutic effects and mechanisms are not yet well understood. MATERIALS AND METHODS: In this study, a UPLC/TOF-MS-based metabolomic study was conducted to explore potential biomarkers that will increase our understanding of cerebral ischemia and to assess the integral efficacy of BNC in a middle cerebral artery occlusion (MCAO) rat model. Plasma metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis. RESULTS: Clear separations were observed between the sham, MCAO and BNC-treated groups. We identified twenty-eight biomarkers in the MCAO rats using variable importance for the projections (VIP) values (VIP>1) and a t-test (P<0.05). The identified biomarkers were mainly related to disturbances in monoamine neurotransmitter metabolism, amino acid metabolism, energy metabolism and lipid metabolism. Moreover, a correlation network diagram of the plasma biomarkers perturbed by MCAO was constructed. Some biomarkers, such as glutamine, PE (17:0), LysoPE (20:1), LysoPE (24:0), and the ratios of LysoPE (24:1) to LysoPE (24:0), LysoPE (24:2) to LysoPE (24:0), showed obvious changes and a tendency for returning to baseline values in BNC-treated MCAO rats. In addition, MCAO rats receiving BNC treatment had improved neurological deficits and reduced cerebral infarct size demonstrating the therapeutic potential of BNC for treating cerebral ischemia. CONCLUSION: This study provides a useful approach for exploring the mechanism of MCAO-induced cerebral ischemia and evaluating the efficacy of BNC. PMID: 26806568 [PubMed - as supplied by publisher]

Homocysteine in embryo culture media as a predictor of pregnancy outcome in assisted reproductive technology. Gynecol Endocrinol. 2016 Jan 24;:1-3 Authors: Boyama BA, Cepni I, Imamoglu M, Oncul M, Tuten A, Yuksel MA, Kervancioglu ME, Kaleli S, Ocal P Abstract The aim of this study was to determine whether homocysteine (hcy) concentrations in embryo culture media correlate with pregnancy outcome in assisted reproductive technology (ART) cycles. Forty patients who underwent single embryo transfer at the infertility clinic of a tertiary care center were recruited for this case-control study. Spent embryo culture media from all patients were collected after single embryo transfer on day 3 (n = 40). Hcy concentrations in embryo culture media were analyzed by enzyme cycling method. Patients were grouped according to the diagnosis of a clinical pregnancy. Sixteen patients were pregnant while 24 patients failed to achieve conception. Mean Hcy levels in the culture media were significantly different between the groups (p < 0.003), as 4.58 ± 1.31 μmol/l in the non-pregnant group and 3.37 ± 0.92 μmol/l in the pregnant group. Receiver operator curve analysis for determining the diagnostic potential of Hcy for pregnancy revealed an area under the curve of 0.792 (confidence interval: 0.65-0.94; p < 0.05). A cut-off value of 3.53 μmol/l was determined with a sensitivity of 83.3%, and a specificity of 68.8%. Lower hcy levels were associated with a better chance of pregnancy and better embryo grades. Hcy may be introduced as an individual metabolomic profiling marker for embryos. PMID: 26806445 [PubMed - as supplied by publisher]

Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals. Alzheimers Dement. 2016 Jan 21; Authors: Casanova R, Varma S, Simpson B, Kim M, An Y, Saldana S, Riveros C, Moscato P, Griswold M, Sonntag D, Wahrheit J, Klavins K, Jonsson PV, Eiriksdottir G, Aspelund T, Launer LJ, Gudnason V, Quigley CL, Thambisetty M Abstract Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive of conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] = 0.92, sensitivity/specificity of 90%/90%). We failed to replicate these findings in a substantially larger study from two independent cohorts-the Baltimore Longitudinal Study of Aging ([BLSA], n = 93, AUC = 0.642, sensitivity/specificity of 51.6%/65.7%) and the Age, Gene/Environment Susceptibility-Reykjavik Study ([AGES-RS], n = 100, AUC = 0.395, sensitivity/specificity of 47.0%/36.0%). In analyses applying machine learning methods to all 187 metabolite concentrations assayed, we find a modest signal in the BLSA with distinct metabolites associated with the preclinical and symptomatic stages of AD, whereas the same methods gave poor classification accuracies in the AGES-RS samples. We believe that ours is the largest blood biomarker study of preclinical AD to date. These findings underscore the importance of large-scale independent validation of index findings from biomarker studies with relatively small sample sizes. PMID: 26806385 [PubMed - as supplied by publisher]