Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy.

Sat, 07/05/2016 - 15:21
Related Articles Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy. Mol Cancer. 2014;13:197 Authors: Shao W, Gu J, Huang C, Liu D, Huang H, Huang Z, Lin Z, Yang W, Liu K, Lin D, Ji T Abstract BACKGROUND: Ambiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring. METHODS: We conducted (1)H nuclear magnetic resonance (NMR)-based metabolic analysis on cell lines (CHG5, SHG44, U87, U118, U251) developed from gliomas of different malignant grades (WHO II and WHO IV). Several methods were applied to analyze the (1)H-NMR spectral data of polar extracts of cell lines and to identify characteristic metabolites, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), fuzzy c-means clustering (FCM) analysis and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). The expression analyses of glial fibrillary acidic protein (GFAP) and matrix metal proteinases (MMP-9) were used to assess malignant behaviors of cell lines. GeneGo pathway analysis was used to associate characteristic metabolites with malignant behavior protein markers GFAP and MMP-9. RESULTS: Stable and distinct metabolic profiles of the five cell lines were obtained. The metabolic profiles of the low malignancy grade group (CHG5, SHG44) were clearly distinguished from those of the high malignancy grade group (U87, U118, U251). Seventeen characteristic metabolites were identified that could distinguish the metabolic profiles of the two groups, nine of which were mapped to processes related to GFAP and MMP-9. Furthermore, the results from both quantitative comparison and metabolic correlation analysis indicated that the significantly altered metabolites were primarily involved in perturbation of metabolic pathways of tricarboxylic acid (TCA) cycle anaplerotic flux, amino acid metabolism, anti-oxidant mechanism and choline metabolism, which could be correlated with the changes in the glioma cells' malignant behaviors. CONCLUSIONS: Our results reveal the metabolic heterogeneity of glioma cell lines with different degrees of malignancy. The obtained metabolic profiles and characteristic metabolites are closely associated with the malignant features of glioma cells, which may lay the basis for both determining the molecular mechanisms underlying glioma malignant transformation and exploiting non-invasive biomarkers for prognosis monitoring. PMID: 25163530 [PubMed - indexed for MEDLINE]

Integrated proteomic and metabolomic analysis to assess the effects of pure and benzo[a]pyrene-loaded carbon black particles on energy metabolism and motility in the human endothelial cell line EA.hy926.

Sat, 07/05/2016 - 15:21
Related Articles Integrated proteomic and metabolomic analysis to assess the effects of pure and benzo[a]pyrene-loaded carbon black particles on energy metabolism and motility in the human endothelial cell line EA.hy926. Arch Toxicol. 2014 Apr;88(4):913-34 Authors: Pink M, Verma N, Rettenmeier AW, Schmitz-Spanke S Abstract Epidemiological studies suggest that environmental exposure to airborne particulate matter may promote cardiovascular diseases; however, it is not clear whether this observation actually reflects exposure to nanosized particles in the environment. In the present study, the human endothelial cell line EA.hy926 was exposed to pure carbon black and, to mimic exposure to diesel exhaust, carbon black loaded with benzo[a]pyrene to ascertain effects of these particles on the cell proteome and metabolom. Particular emphasis was laid on an extended exposure period (14 days) and a low particle concentration (100 ng/mL). While ROS production essentially remained unaffected, exposure of the cells to the particles resulted in a significantly enhanced cell proliferation. Evaluation of the obtained proteomic and phosphoproteomic data revealed modulations of proteins involved in catalytic processes and cytoskeleton maintenance. The bioinformatic evaluation of the data revealed the possible involvement of the transcription factor peroxisome proliferator-activated receptor gamma. The further analysis of the cytoskeleton indicated changes of the cell motility, which is in agreement with an observed increase in the cellular migration and invasion, and macroscopic changes of the cytoskeleton of the exposed cells. PMID: 24464499 [PubMed - indexed for MEDLINE]

metabolomics; +18 new citations

Fri, 06/05/2016 - 14:26
18 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 2016/05/06PubMed 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.

Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet-induced obese mice.

Thu, 05/05/2016 - 13:39
Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet-induced obese mice. Mol Nutr Food Res. 2016 May 4; Authors: Park HS, Hur HJ, Kim SH, Park SJ, Hong MJ, Sung MJ, Kwon DY, Kim MS Abstract SCOPE: Natural compounds that regulate peroxisome proliferator-activated receptor alpha (PPARα) have been reported to have beneficial effects in obesity-mediated metabolic disorders. In this study, we demonstrated that biochanin A (BA), an agonist of PPARα, improved hepatic steatosis and insulin resistance by regulating hepatic lipid and glucose metabolism. METHODS AND RESULTS: C57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), and a HFD supplemented with 0.05% BA for 12 weeks. Histological and biochemical examinations indicated that BA prevented obesity-induced hepatic steatosis and insulin resistance in HFD-fed mice. BA stimulated the transcriptional activation of PPARα in vitro and increased the expression of PPARα and its regulatory proteins in the liver. CE-TOF/MS analyses indicated that BA administration promoted the recovery of metabolites involved in phosphatidylcholine synthesis, lipogenesis, and beta-oxidation in the livers of obese mice. BA also suppressed the levels of gluconeogenesis-related metabolites and the expression of the associated enzymes, glucose 6-phosphatase and pyruvate kinase. CONCLUSION: Taken together, these results showed that BA ameliorated metabolic disorders such as hepatic steatosis and insulin resistance by modulating lipid and glucose metabolism in diet-induced obesity. Thus, BA may be a potential therapeutic agent for the prevention of obesity-mediated hepatic steatosis and insulin resistance. This article is protected by copyright. All rights reserved. PMID: 27145114 [PubMed - as supplied by publisher]

Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress.

Thu, 05/05/2016 - 13:39
Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress. Nanotoxicology. 2016 May 4;:1-13 Authors: Carrola J, Bastos V, Jarak I, Oliveira-Silva R, Malheiro E, Daniel-da-Silva AL, Oliveira H, Santos C, Gil AM, Duarte IF Abstract The widespread use of silver nanoparticles (AgNPs) is accompanied by a growing concern regarding their potential risks to human health, thus calling for an increased understanding of their biological effects. The aim of this work was to systematically study the extent to which changes in cellular metabolism were dependent on the properties of AgNPs, using NMR metabolomics. Human skin keratinocytes (HaCaT cells) were exposed to citrate-coated AgNPs of 10, 30 or 60 nm diameter and to 30 nm AgNPs coated either with citrate (CIT), polyethylene glycol (PEG) or bovine serum albumin (BSA), to assess the influence of NP size and surface chemistry. Overall, CIT-coated 60 nm and PEG-coated 30 nm AgNPs had the least impact on cell viability and metabolism. The role of ionic silver and reactive oxygen species (ROS)-mediated effects was also studied, in comparison to CIT-coated 30 nm particles. At concentrations causing an equivalent decrease in cell viability, Ag(+ )ions produced a change in the metabolic profile that was remarkably similar to that seen for AgNPs, the main difference being the lesser impact on the Krebs cycle and energy metabolism. Finally, this study newly reported that while down-regulated glycolysis and disruption of energy production were common to AgNPs and H2O2, the impact on some metabolic pathways (GSH synthesis, glutaminolysis and the Krebs cycle) was independent of ROS-mediated mechanisms. In conclusion, this study shows the ability of NMR metabolomics to define subtle biochemical changes induced by AgNPs and demonstrates the potential of this approach for rapid, untargeted screening of pre-clinical toxicity of nanomaterials in general. PMID: 27144425 [PubMed - as supplied by publisher]

The application of high-resolution mass spectrometry-based data-mining tools in tandem to metabolite profiling of a triple drug combination in humans.

Thu, 05/05/2016 - 13:39
Related Articles The application of high-resolution mass spectrometry-based data-mining tools in tandem to metabolite profiling of a triple drug combination in humans. Anal Chim Acta. 2015 Oct 15;897:34-44 Authors: Xing J, Zang M, Zhang H, Zhu M Abstract Patients are usually exposed to multiple drugs, and metabolite profiling of each drug in complex biological matrices is a big challenge. This study presented a new application of an improved high resolution mass spectrometry (HRMS)-based data-mining tools in tandem to fast and comprehensive metabolite identification of combination drugs in human. The model drug combination was metronidazole-pantoprazole-clarithromycin (MET-PAN-CLAR), which is widely used in clinic to treat ulcers caused by Helicobacter pylori. First, mass defect filter (MDF), as a targeted data processing tool, was able to recover all relevant metabolites of MET-PAN-CLAR in human plasma and urine from the full-scan MS dataset when appropriate MDF templates for each drug were defined. Second, the accurate mass-based background subtraction (BS), as an untargeted data-mining tool, worked effectively except for several trace metabolites, which were buried in the remaining background signals. Third, an integrated strategy, i.e., untargeted BS followed by improved MDF, was effective for metabolite identification of MET-PAN-CLAR. Most metabolites except for trace ones were found in the first step of BS-processed datasets, and the results led to the setup of appropriate metabolite MDF template for the subsequent MDF data processing. Trace metabolites were further recovered by MDF, which used both common MDF templates and the novel metabolite-based MDF templates. As a result, a total of 44 metabolites or related components were found for MET-PAN-CLAR in human plasma and urine using the integrated strategy. New metabolic pathways such as N-glucuronidation of PAN and dehydrogenation of CLAR were found. This study demonstrated that the combination of accurate mass-based multiple data-mining techniques in tandem, i.e., untargeted background subtraction followed by targeted mass defect filtering, can be a valuable tool for rapid metabolite profiling of combination drugs in vivo. PMID: 26515003 [PubMed - indexed for MEDLINE]

Monitoring of drug intake during pregnancy by questionnaires and LC-MS/MS drug urine screening: evaluation of both monitoring methods.

Thu, 05/05/2016 - 13:39
Related Articles Monitoring of drug intake during pregnancy by questionnaires and LC-MS/MS drug urine screening: evaluation of both monitoring methods. Drug Test Anal. 2015 Aug;7(8):695-702 Authors: Hoeke H, Roeder S, Bertsche T, Lehmann I, Borte M, von Bergen M, Wissenbach DK Abstract Various studies pointed towards a relationship between chronic diseases such as asthma and allergy and environmental risk factors, which are one aspect of the so-called Exposome. These environmental risk factors include also the intake of drugs. One critical step in human development is the prenatal period, in which exposures might have critical impact on the child's health outcome. Thereby, the health effects of drugs taken during gestation are discussed controversially with regard to newborns' disease risk. Due to this, the drug intake of pregnant women in the third trimester was monitored by questionnaire, in addition to biomonitoring using a local birth cohort study, allowing correlations of drug exposure with disease risk. Therefore, 622 urine samples were analyzed by an untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) urine screening and the results were compared to self-administered questionnaires. In total, 48% (n = 296) reported an intake of pharmaceuticals, with analgesics as the most frequent reported drug class in addition to dietary supplements. 182 times compounds were detected by urine screening, with analgesics (42%; n = 66) as the predominantly drug class. A comparison of reported and detected drug intake was performed for three different time spans between completion of the questionnaires and urine sampling. Even if the level of accordance was low in general, similar percentages (~25%, ~19%, and ~ 20%) were found for all groups. This study illustrates that a comprehensive evaluation of drug intake is neither achieved by questionnaires nor by biomonitoring alone. Instead, a combination of both monitoring methods, providing complementary information, should be considered. PMID: 25545167 [PubMed - indexed for MEDLINE]

(1)H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis.

Wed, 04/05/2016 - 12:38
(1)H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis. Int J Reprod Biomed (Yazd). 2016 Jan;14(1):1-8 Authors: Ghazi N, Arjmand M, Akbari Z, Mellati AO, Saheb-Kashaf H, Zamani Z Abstract BACKGROUND: So far, non-invasive diagnostic approaches such as ultrasound, magnetic resonance imaging, or blood tests do not have sufficient diagnostic power for endometriosis disease. Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. OBJECTIVE: The present study focuses on the identification of predictive biomarkers in serum by pattern recognition techniques and uses partial least square discriminant analysis, multi-layer feed forward artificial neural networks (ANNs) and quadratic discriminant analysis (QDA) modeling tools for the early diagnosis of endometriosis in a minimally invasive manner by (1)H- NMR based metabolomics. MATERIALS AND METHODS: This prospective cohort study was done in Pasteur Institute, Iran in June 2013. Serum samples of 31 infertile women with endometriosis (stage II and III) who confirmed by diagnostic laparoscopy and 15 normal women were collected and analyzed by nuclear magnetic resonance spectroscopy. The model was built by using partial least square discriminant analysis, QDA, and ANNs to determine classifier metabolites for early prediction risk of disease. RESULTS: The levels of 2- methoxyestron, 2-methoxy estradiol, dehydroepiandrostion androstendione, aldosterone, and deoxy corticosterone were enhanced significantly in infertile group. While cholesterol and primary bile acids levels were decreased. QDA model showed significant difference between two study groups. Positive and negative predict value levels obtained about 71% and 78%, respectively. ANNs provided also criteria for detection of endometriosis. CONCLUSION: The QDA and ANNs modeling can be used as computational tools in noninvasive diagnose of endometriosis. However, the model designed by QDA methods is more efficient compared to ANNs in diagnosis of endometriosis patients. PMID: 27141542 [PubMed - as supplied by publisher]

Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy.

Wed, 04/05/2016 - 12:38
Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy. Oncoimmunology. 2016 Mar;5(3):e1088631 Authors: Iribarren K, Bloy N, Buqué A, Cremer I, Eggermont A, Fridman WH, Fucikova J, Galon J, Špíšek R, Zitvogel L, Kroemer G, Galluzzi L Abstract Accumulating preclinical evidence indicates that Toll-like receptor (TLR) agonists efficiently boost tumor-targeting immune responses (re)initiated by most, if not all, paradigms of anticancer immunotherapy. Moreover, TLR agonists have been successfully employed to ameliorate the efficacy of various chemotherapeutics and targeted anticancer agents, at least in rodent tumor models. So far, only three TLR agonists have been approved by regulatory agencies for use in cancer patients. Moreover, over the past decade, the interest of scientists and clinicians in these immunostimulatory agents has been fluctuating. Here, we summarize recent advances in the preclinical and clinical development of TLR agonists for cancer therapy. PMID: 27141345 [PubMed - as supplied by publisher]

Prime time for immune-checkpoint targeted therapy at ASCO 2015.

Wed, 04/05/2016 - 12:38
Prime time for immune-checkpoint targeted therapy at ASCO 2015. Oncoimmunology. 2016 Mar;5(3):e1068494 Authors: Marabelle A, Routy B, Michels J, Kroemer G, Zitvogel L Abstract Cancer immunotherapy has been one of the dominant topics in oral presentations and abstracts during the 2015 annual meeting of the American Society of Clinical Oncology (ASCO). The renewed interest in immunotherapy is explained by the wide spectrum of activity, the durability of tumor responses and the rapid clinical development of immune-checkpoint targeted monoclonal antibodies. These new drugs are currently revolutionizing the field of oncology. Here we highlight what were to us the most important results announced during the annual meeting of ASCO held in Chicago, IL from May, 29th to June, 2nd 2015. In addition, we searched all the posters/published abstracts pertinent to the field of immunooncology from this year conference. Among more than 400 published abstracts on this topic, we have grouped and briefly summarized the most relevant ones. PMID: 27141332 [PubMed - as supplied by publisher]

Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells.

Wed, 04/05/2016 - 12:38
Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells. Cancer Metab. 2016;4:9 Authors: Borrego SL, Fahrmann J, Datta R, Stringari C, Grapov D, Zeller M, Chen Y, Wang P, Baldi P, Gratton E, Fiehn O, Kaiser P Abstract BACKGROUND: The majority of cancer cells have a unique metabolic requirement for methionine that is not observed in normal, non-tumorigenic cells. This phenotype is described as "methionine dependence" or "methionine stress sensitivity" in which cancer cells are unable to proliferate when methionine has been replaced with its metabolic precursor, homocysteine, in cell culture growth media. We focus on the metabolic response to methionine stress in the triple negative breast cancer cell line MDA-MB-468 and its methionine insensitive derivative cell line MDA-MB-468res-R8. RESULTS: Using a variety of techniques including fluorescence lifetime imaging microscopy (FLIM) and extracellular flux assays, we identified a metabolic down-regulation of oxidative phosphorylation in both MDA-MB-468 and MDA-MB-468res-R8 cell types when cultured in homocysteine media. Untargeted metabolomics was performed by way of gas chromatography/time-of-flight mass spectrometry on both cell types cultured in homocysteine media over a period of 2 to 24 h. We determined unique metabolic responses between the two cell lines in specific pathways including methionine salvage, purine/pyrimidine synthesis, and the tricarboxylic acid cycle. Stable isotope tracer studies using deuterium-labeled homocysteine indicated a redirection of homocysteine metabolism toward the transsulfuration pathway and glutathione synthesis. This data corroborates with increased glutathione levels concomitant with increased levels of oxidized glutathione. Redirection of homocysteine flux resulted in reduced generation of methionine from homocysteine particularly in MDA-MB-468 cells. Consequently, synthesis of the important one-carbon donor S-adenosylmethionine (SAM) was decreased, perturbing the SAM to S-adenosylhomocysteine ratio in MDA-MB-468 cells, which is an indicator of the cellular methylation potential. CONCLUSION: This study indicates a differential metabolic response between the methionine sensitive MDA-MB-468 cells and the methionine insensitive derivative cell line MDA-MB-468res-R8. Both cell lines appear to experience oxidative stress when methionine was replaced with its metabolic precursor homocysteine, forcing cells to redirect homocysteine metabolism toward the transsulfuration pathway to increase glutathione synthesis. The methionine stress resistant MDA-MB-468res-R8 cells responded to this cellular stress earlier than the methionine stress sensitive MDA-MB468 cells and coped better with metabolic demands. Additionally, it is evident that S-adenosylmethionine metabolism is dependent on methionine availability in cancer cells, which cannot be sufficiently supplied by homocysteine metabolism under these conditions. PMID: 27141305 [PubMed - as supplied by publisher]

Low-level environmental phthalate exposure associates with urine metabolome alteration in a Chinese male cohort.

Wed, 04/05/2016 - 12:38
Low-level environmental phthalate exposure associates with urine metabolome alteration in a Chinese male cohort. Environ Sci Technol. 2016 May 3; Authors: Zhang J, Liu L, Wang X, Huang Q, Tian M, Shen H Abstract The general population is exposed to phthalates through various sources and routes. Integration of omics data and epidemiological data is a key step towards directly linking phthalate bio-monitoring data with biological response. Urine metabolomics is a powerful tool to identify exposure biomarkers and delineate the modes of action of environmental stressors. The objectives of this study are to investigate the association between low-level environmental phthalate exposure and urine metabolome alteration in male population, and to unveil the metabolic pathways involved in the mechanisms of phthalate toxicity. In this retrospective cross-sectional study, we studied the urine metabolomic profiles of 364 male subjects exposed to low-level environmental phthalates. Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are the most widely used phthalates. ΣDEHP and MBP (the major metabolite of DBP) were associated with significant alteration of global urine metabolome in the male population. We observed significant increase in the levels of acetylneuraminic acid, carnitine C8:1, carnitine C18:0, cystine, phenylglycine, phenylpyruvic acid and glutamylphenylalanine; and meanwhile, decrease in the levels of carnitine C16:2, diacetylspermine, alanine, taurine, tryptophan, ornithine, methylglutaconic acid, hydroxyl-PEG2 and keto-PGE2 in high exposure group. The observations indicated that low-level environmental phthalate exposure associated with increased oxidative stress and fatty acid oxidation and decreased prostaglandin metabolism. Urea cycle, tryptophan and phenylalanine metabolism disruption was also observed. The urine metabolome disruption effects associated with ΣDEHP and MEP were similar, but not identical. The multi-biomarker models presented AUC values of 0.845 and 0.834 for ΣDEHP and MEP, respectively. The predictive accuracy rates of established models were 81% for ΣDEHP and 73% for MEP. Our results suggest that low-level environmental phthalate exposure associates with urine metabolome disruption in male population, providing new insight into the early molecular events of phthalate exposure. PMID: 27138838 [PubMed - as supplied by publisher]

Non-targeted metabolomics identified a common metabolic signature of lethal ventricular tachyarrhythmia (LVTA) in two rat models.

Wed, 04/05/2016 - 12:38
Non-targeted metabolomics identified a common metabolic signature of lethal ventricular tachyarrhythmia (LVTA) in two rat models. Mol Biosyst. 2016 May 3; Authors: Wang X, Wang D, Yu X, Zhang G, Wu J, Zhu G, Su R, Lv J Abstract Lethal ventricular tachyarrhythmia (LVTA) is the predominant underlying mechanism of sudden cardiac death (SCD). The aim of this study is to characterize the metabolic features of myocardia following LVTA, and identify potential biomarkers to diagnose LVTA. We developed two LVTA rat models induced by aconitine injection or coronary artery ligation, which represent cardiac ion channel disease-related and cardiac ischemia-related SCD, respectively. The myocardial metabolic profile was investigated by gas chromatography-mass spectrometry and proton nuclear magnetic resonance-based metabolomics. Twenty-three aconitine-injected and 14 coronary artery ligation-treated rats developed LVTA SCD. A total of 38 differential metabolites of myocardia were identified in aconitine-induced LVTA rats, of which 31 metabolites showed a similar change in coronary artery ligation-related LVTA rats. Fatty acids (stearic, palmitic, linoleic, elaidic, and myristic) and branched-chain amino acids (valine, leucine, and isoleucine) were the most down-regulated metabolites. Furthermore, elevated ADP, phosphate, lactate, glutamate, aspartate, threonine, choline and arginine were also observed. Major pathways regarding these dysregulated metabolites post LVTA are energy excessive consumption and deficit, ionic imbalance, oxidative stress, cardiac cytotoxicity and membrane injury. Valine, stearic acid and leucine collectively enable a precision of 92.9% to distinguish LVTA from its control, and are correlated with several arrhythmia indices. Our results uncovered a common metabolic feature of LVTA in myocardia in two rat models, which represent cardiac ion channel disease and cardiac ischemia, respectively. l-Valine, l-leucine and stearic acid jointly confer good potential for distinguishing LVTA, which might be potential biomarkers of LVTA-related SCD. PMID: 27138062 [PubMed - as supplied by publisher]

SWAPDT: A method for Short-time Withering Assessment of Probability for Drought Tolerance in Camellia sinensis validated by targeted metabolomics.

Wed, 04/05/2016 - 12:38
SWAPDT: A method for Short-time Withering Assessment of Probability for Drought Tolerance in Camellia sinensis validated by targeted metabolomics. J Plant Physiol. 2016 Apr 19;198:39-48 Authors: Nyarukowa C, Koech R, Loots T, Apostolides Z Abstract Climate change is causing droughts affecting crop production on a global scale. Classical breeding and selection strategies for drought-tolerant cultivars will help prevent crop losses. Plant breeders, for all crops, need a simple and reliable method to identify drought-tolerant cultivars, but such a method is missing. Plant metabolism is often disrupted by abiotic stress conditions. To survive drought, plants reconfigure their metabolic pathways. Studies have documented the importance of metabolic regulation, i.e. osmolyte accumulation such as polyols and sugars (mannitol, sorbitol); amino acids (proline) during drought. This study identified and quantified metabolites in drought tolerant and drought susceptible Camellia sinensis cultivars under wet and drought stress conditions. For analyses, GC-MS and LC-MS were employed for metabolomics analysis.%RWC results show how the two drought tolerant and two drought susceptible cultivars differed significantly (p≤0.05) from one another; the drought susceptible exhibited rapid water loss compared to the drought tolerant. There was a significant variation (p<0.05) in metabolite content (amino acid, sugars) between drought tolerant and drought susceptible tea cultivars after short-time withering conditions. These metabolite changes were similar to those seen in other plant species under drought conditions, thus validating this method. The Short-time Withering Assessment of Probability for Drought Tolerance (SWAPDT) method presented here provides an easy method to identify drought tolerant tea cultivars that will mitigate the effects of drought due to climate change on crop losses. PMID: 27137993 [PubMed - as supplied by publisher]

Bridging the Gaps: the Promise of Omics Studies in Pediatric Exercise Research.

Wed, 04/05/2016 - 12:38
Bridging the Gaps: the Promise of Omics Studies in Pediatric Exercise Research. Pediatr Exerc Sci. 2016 May;28(2):194-201 Authors: Radom-Aizik S, Cooper DM Abstract In this review, we highlight promising new discoveries that may generate useful and clinically relevant insights into the mechanisms that link exercise with growth during critical periods of development. Growth in childhood and adolescence is unique among mammals and is a dynamic process regulated by an evolution of hormonal and inflammatory mediators, age-dependent progression of gene expression, and environmentally modulated epigenetic mechanisms. Many of these same processes likely affect molecular transducers of physical activity. How the molecular signaling associated with growth is synchronized with signaling associated with exercise is poorly understood. Recent advances in "omics"-namely genomics and epigenetics, metabolomics, and proteomics-now provide exciting approaches and tools that can be used for the first time to address this gap. A biologic definition of "healthy" exercise that links the metabolic transducers of physical activity with parallel processes that regulate growth will transform health policy and guidelines that promote optimal use of physical activity. PMID: 27137166 [PubMed - as supplied by publisher]

Profiling the Oxylipin and Endocannabinoid Metabolome by UPLC-ESI-MS/MS in Human Plasma to Monitor Postprandial Inflammation.

Wed, 04/05/2016 - 12:38
Related Articles Profiling the Oxylipin and Endocannabinoid Metabolome by UPLC-ESI-MS/MS in Human Plasma to Monitor Postprandial Inflammation. PLoS One. 2015;10(7):e0132042 Authors: Gouveia-Figueira S, Späth J, Zivkovic AM, Nording ML Abstract Bioactive lipids, including oxylipins, endocannabinoids, and related compounds may function as specific biochemical markers of certain aspects of inflammation. However, the postprandial responsiveness of these compounds is largely unknown; therefore, changes in the circulating oxylipin and endocannabinoid metabolome in response to a challenge meal were investigated at six occasions in a subject who freely modified her usual diet. The dietary change, and especially the challenge meal itself, represented a modification of precursor fatty acid status, with expectedly subtle effects on bioactive lipid levels. To detect even the slightest alteration, highly sensitive ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS/MS) methods for bioactive lipid profiling was employed. A previously validated UPLC-ESI-MS/MS method for profiling the endocannabinoid metabolome was used, while validation of an UPLC-ESI-MS/MS method for oxylipin analysis was performed with acceptable outcomes for a majority of the parameters according to the US Food and Drug Administration guidelines for linearity (0.9938 < R2 < 0.9996), limit of detection (0.0005-2.1 pg on column), limit of quantification (0.0005-4.2 pg on column), inter- and intraday accuracy (85-115%) and precision (< 5%), recovery (40-109%) and stability (40-105%). Forty-seven of fifty-two bioactive lipids were detected in plasma samples at fasting and in the postprandial state (0.5, 1, and 3 hours after the meal). Multivariate analysis showed a significant shift of bioactive lipid profiles in the postprandial state due to inclusion of dairy products in the diet, which was in line with univariate analysis revealing seven compounds (NAGly, 9-HODE, 13-oxo-ODE, 9(10)-EpOME, 12(13)-EpOME, 20-HETE, and 11,12-DHET) that were significantly different between background diets in the postprandial state (but not at fasting). The only change in baseline levels at fasting was displayed by TXB2. Furthermore, postprandial responsiveness was detected for seven compounds (POEA, SEA, 9(10)-DiHOME, 12(13)-DiHOME, 13-oxo-ODE, 9-HODE, and 13-HODE). Hence, the data confirm that the UPLC-ESI-MS/MS method performance was sufficient to detect i) a shift, in the current case most notably in the postprandial bioactive lipid metabolome, caused by changes in diet and ii) responsiveness to a challenge meal for a subset of the oxylipin and endocannabinoid metabolome. To summarize, we have shown proof-of-concept of our UPLC-ESI-MS/MS bioactive lipid protocols for the purpose of monitoring subtle shifts, and thereby useful to address lipid-mediated postprandial inflammation. PMID: 26186333 [PubMed - indexed for MEDLINE]

Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

Wed, 04/05/2016 - 12:38
Related Articles Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose. PLoS One. 2015;10(7):e0132088 Authors: Zhou YY, Ji XF, Fu JP, Zhu XJ, Li RH, Mu CK, Wang CL, Song WW Abstract D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance. PMID: 26176541 [PubMed - indexed for MEDLINE]

metabolomics; +24 new citations

Tue, 03/05/2016 - 14:53
24 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 2016/05/03PubMed 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.

EIder: A compound identification tool for gas chromatography mass spectrometry data.

Mon, 02/05/2016 - 14:16
Related Articles EIder: A compound identification tool for gas chromatography mass spectrometry data. J Chromatogr A. 2016 Apr 23; Authors: Koo I, Kim S, Shi B, Lorkiewicz P, Song M, McClain C, Zhang X Abstract We report software entitled EIder (EI mass spectrum identifier) that provides users with eight literature reported spectrum matching algorithms for compound identification from gas chromatography mass spectrometry (GC-MS) data. EIder calculates retention index according to experimental conditions categorized by column class, column type and data type, where 9 empirical distribution functions of the absolute retention index deviation to its mean value were constructed using the National Institute of Standards and Technology (NIST) 2011 retention index database to improve the accuracy of compound identification. EIder filters compound candidates based on elementary composition and derivatization reagent, and automatically adds the molecular information of the native compound to each derivatized compound using a manually created database. When multiple samples are analyzed together, EIder performs cross-sample alignment and provides an option of using an average mass spectrum for compound identification. Furthermore, a suite of graphical user interfaces are implemented in EIder to allow users to both manually and automatically modify the identification results using experimental information at various analysis stages. Analysis of three types of GC-MS datasets indicates that the developed EIder software can improve the accuracy of compound identification. PMID: 27131963 [PubMed - as supplied by publisher]

Effect of organochlorine pesticides exposure on the maize root metabolome assessed using high-resolution magic-angle spinning (1)H NMR spectroscopy.

Mon, 02/05/2016 - 14:16
Related Articles Effect of organochlorine pesticides exposure on the maize root metabolome assessed using high-resolution magic-angle spinning (1)H NMR spectroscopy. Environ Pollut. 2016 Apr 28;214:539-548 Authors: Blondel C, Khelalfa F, Reynaud S, Fauvelle F, Raveton M Abstract (1)H-HRMAS NMR-based metabolomics was used to better understand the toxic effects on maize root tips of organochlorine pesticides (OCPs), namely lindane (γHCH) and chlordecone (CLD). Maize seedlings were exposed to 2.5 μM γHCH (mimicking basic environmental contaminations) for 7 days and compared to 2.5 μM CLD and 25 μM γHCH for 7 days (mimicking hot spot contaminations). The (1)H-HRMAS NMR-based metabolomic profiles provided details of the changes in carbohydrates, amino acids, tricarboxylic acid (TCA) cycle intermediates and fatty acids with a significant separation between the control and OCP-exposed root tips. First of all, alterations in the balance between glycolysis/gluconeogenesis were observed with sucrose depletion and with dose-dependent fluctuations in glucose content. Secondly, observations indicated that OCPs might inactivate the TCA cycle, with sizeable succinate and fumarate depletion. Thirdly, disturbances in the amino acid composition (GABA, glutamine/glutamate, asparagine, isoleucine) reflected a new distribution of internal nitrogen compounds under OCP stress. Finally, OCP exposure caused an increase in fatty acid content, concomitant with a marked rise in oxidized fatty acids which could indicate failures in cell integrity and vitality. Moreover, the accumulation of asparagine and oxidized fatty acids with the induction of LOX3 transcription levels under OCP exposure highlighted an induction of protein and lipid catabolism. The overall data indicated that the effect of OCPs on primary metabolism could have broader physiological consequences on root development. Therefore, (1)H-HRMAS NMR metabolomics is a sensitive tool for understanding molecular disturbances under OCP exposure and can be used to perform a rapid assessment of phytotoxicity. PMID: 27131813 [PubMed - as supplied by publisher]

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