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

Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection.

Wed, 16/09/2015 - 13:44
Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection. J Chromatogr A. 2015 Sep 8; Authors: Xu Y, Dou D, Ran X, Liu C, Chen J Abstract Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction. PMID: 26372445 [PubMed - as supplied by publisher]

Integration of high-content screening and untargeted metabolomics for comprehensive functional annotation of natural product libraries.

Wed, 16/09/2015 - 13:44
Integration of high-content screening and untargeted metabolomics for comprehensive functional annotation of natural product libraries. Proc Natl Acad Sci U S A. 2015 Sep 14; Authors: Kurita KL, Glassey E, Linington RG Abstract Traditional natural products discovery using a combination of live/dead screening followed by iterative bioassay-guided fractionation affords no information about compound structure or mode of action until late in the discovery process. This leads to high rates of rediscovery and low probabilities of finding compounds with unique biological and/or chemical properties. By integrating image-based phenotypic screening in HeLa cells with high-resolution untargeted metabolomics analysis, we have developed a new platform, termed Compound Activity Mapping, that is capable of directly predicting the identities and modes of action of bioactive constituents for any complex natural product extract library. This new tool can be used to rapidly identify novel bioactive constituents and provide predictions of compound modes of action directly from primary screening data. This approach inverts the natural products discovery process from the existing ‟grind and find" model to a targeted, hypothesis-driven discovery model where the chemical features and biological function of bioactive metabolites are known early in the screening workflow, and lead compounds can be rationally selected based on biological and/or chemical novelty. We demonstrate the utility of the Compound Activity Mapping platform by combining 10,977 mass spectral features and 58,032 biological measurements from a library of 234 natural products extracts and integrating these two datasets to identify 13 clusters of fractions containing 11 known compound families and four new compounds. Using Compound Activity Mapping we discovered the quinocinnolinomycins, a new family of natural products with a unique carbon skeleton that cause endoplasmic reticulum stress. PMID: 26371303 [PubMed - as supplied by publisher]

Contribution of Colonic Fermentation and Fecal Water Toxicity to the Pathophysiology of Lactose-Intolerance.

Wed, 16/09/2015 - 13:44
Contribution of Colonic Fermentation and Fecal Water Toxicity to the Pathophysiology of Lactose-Intolerance. Nutrients. 2015;7(9):7505-22 Authors: Windey K, Houben E, Deroover L, Verbeke K Abstract Whether or not abdominal symptoms occur in subjects with small intestinal lactose malabsorption might depend on differences in colonic fermentation. To evaluate this hypothesis, we collected fecal samples from subjects with lactose malabsorption with abdominal complaints (LM-IT, n = 11) and without abdominal complaints (LM-T, n = 8) and subjects with normal lactose digestion (NLD, n = 15). Lactose malabsorption was diagnosed using a (13)C-lactose breath test. Colonic fermentation was characterized in fecal samples at baseline and after incubation with lactose for 3 h, 6 h and 24 h through a metabolomics approach using gas chromatography-mass spectrometry (GC-MS). Fecal water cytotoxicity was analyzed using a colorimetric assay. Fecal water cytotoxicity was not different between the three groups (Kruskall-Wallis p = 0.164). Cluster analysis of the metabolite patterns revealed separate clusters for NLD, LM-T and LM-IT samples at baseline and after 24 h incubation with lactose. Levels of 5-methyl-2-furancarboxaldehyde were significantly higher in LM-IT and LM-T compared to NLD whereas those of an unidentified aldehyde were significantly higher in LM-IT compared to LM-T and NLD. Incubation with lactose increased short chain fatty acid (SCFA) concentrations more in LM-IT and LM-T compared to NLD. In conclusion, fermentation patterns were clearly different in NLD, LM-IT and LM-T, but not related to differences in fecal water cytotoxicity. PMID: 26371036 [PubMed - in process]

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study.

Wed, 16/09/2015 - 13:44
First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study. Int J Mol Sci. 2015;16(9):21520-38 Authors: Austdal M, Tangerås LH, Skråstad RB, Salvesen K, Austgulen R, Iversen AC, Bathen TF Abstract Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia. PMID: 26370975 [PubMed - in process]

Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf.

Wed, 16/09/2015 - 13:44
Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf. Molecules. 2015;20(9):16266-77 Authors: Lou Z, Tang Y, Song X, Wang H Abstract Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL(-1). Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I) were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis) and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants. PMID: 26370951 [PubMed - in process]

In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry.

Wed, 16/09/2015 - 13:44
In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry. J Am Soc Mass Spectrom. 2015 Sep 14; Authors: Switzar L, Nicolardi S, Rutten JW, Oberstein SA, Aartsma-Rus A, van der Burgt YE Abstract Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow. A key advantage of a LC-based strategy is the use of the retention time in identifying both intra- and interpeptide disulfide bonds. This is demonstrated by performing two sequential analyses of a certain protein digest, once without and once with electrochemical reduction. In this way, the "parent" disulfide-linked peptide detected in the first run has a retention time-based correlation with the EC-reduced peptides detected in the second run, thus simplifying disulfide bond mapping. Using this platform, both inter- and intra-disulfide-linked peptides were characterized in two different proteins, ß-lactoglobulin and ribonuclease B. In order to prevent disulfide reshuffling during the digestion process, proteins were digested at a relatively low pH, using (a combination of) the high specificity proteases trypsin and Glu-C. With this approach, disulfide bonds in ß-lactoglobulin and ribonuclease B were comprehensively identified and localized, showing that online LC-EC-MS is a useful tool for the characterization of protein disulfide bonds. Graphical Abstract ᅟ. PMID: 26369777 [PubMed - as supplied by publisher]

Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.

Wed, 16/09/2015 - 13:44
Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy. Oncotarget. 2015 Aug 28;6(25):20840-50 Authors: Vacchelli E, Semeraro M, Enot DP, Chaba K, Poirier Colame V, Dartigues P, Perier A, Villa I, Rusakiewicz S, Gronnier C, Goéré D, Mariette C, Zitvogel L, Kroemer G Abstract Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy. PMID: 26369701 [PubMed - in process]

Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants.

Wed, 16/09/2015 - 13:44
Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants. BMC Plant Biol. 2015;15(1):220 Authors: Hagel JM, Mandal R, Han B, Han J, Dinsmore DR, Borchers CH, Wishart DS, Facchini PJ Abstract BACKGROUND: Recent progress toward the elucidation of benzylisoquinoline alkaloid (BIA) metabolism has focused on a small number of model plant species. Current understanding of BIA metabolism in plants such as opium poppy, which accumulates important pharmacological agents such as codeine and morphine, has relied on a combination of genomics and metabolomics to facilitate gene discovery. Metabolomics studies provide important insight into the primary biochemical networks underpinning specialized metabolism, and serve as a key resource for metabolic engineering, gene discovery, and elucidation of governing regulatory mechanisms. Beyond model plants, few broad-scope metabolomics reports are available for the vast number of plant species known to produce an estimated 2500 structurally diverse BIAs, many of which exhibit promising medicinal properties. RESULTS: We applied a multi-platform approach incorporating four different analytical methods to examine 20 non-model, BIA-accumulating plant species. Plants representing four families in the Ranunculales were chosen based on reported BIA content, taxonomic distribution and importance in modern/traditional medicine. One-dimensional (1)H NMR-based profiling quantified 91 metabolites and revealed significant species- and tissue-specific variation in sugar, amino acid and organic acid content. Mono- and disaccharide sugars were generally lower in roots and rhizomes compared with stems, and a variety of metabolites distinguished callus tissue from intact plant organs. Direct flow infusion tandem mass spectrometry provided a broad survey of 110 lipid derivatives including phosphatidylcholines and acylcarnitines, and high-performance liquid chromatography coupled with UV detection quantified 15 phenolic compounds including flavonoids, benzoic acid derivatives and hydroxycinnamic acids. Ultra-performance liquid chromatography coupled with high-resolution Fourier transform mass spectrometry generated extensive mass lists for all species, which were mined for metabolites putatively corresponding to BIAs. Different alkaloids profiles, including both ubiquitous and potentially rare compounds, were observed. CONCLUSIONS: Extensive metabolite profiling combining multiple analytical platforms enabled a more complete picture of overall metabolism occurring in selected plant species. This study represents the first time a metabolomics approach has been applied to most of these species, despite their importance in modern and traditional medicine. Coupled with genomics data, these metabolomics resources serve as a key resource for the investigation of BIA biosynthesis in non-model plant species. PMID: 26369413 [PubMed - in process]

Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice.

Wed, 16/09/2015 - 13:44
Related Articles Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice. Cell Death Dis. 2015;6:e1597 Authors: Wilson CH, Shalini S, Filipovska A, Richman TR, Davies S, Martin SD, McGee SL, Puccini J, Nikolic A, Dorstyn L, Kumar S Abstract Ageing is a complex biological process for which underlying biochemical changes are still largely unknown. We performed comparative profiling of the cellular proteome and metabolome to understand the molecular basis of ageing in Caspase-2-deficient (Casp2(-/-)) mice that are a model of premature ageing in the absence of overt disease. Age-related changes were determined in the liver and serum of young (6-9 week) and aged (18-24 month) wild-type and Casp2(-/-) mice. We identified perturbed metabolic pathways, decreased levels of ribosomal and respiratory complex proteins and altered mitochondrial function that contribute to premature ageing in the Casp2(-/-) mice. We show that the metabolic profile changes in the young Casp2(-/-) mice resemble those found in aged wild-type mice. Intriguingly, aged Casp2(-/-) mice were found to have reduced blood glucose and improved glucose tolerance. These results demonstrate an important role for caspase-2 in regulating proteome and metabolome remodelling during ageing. PMID: 25611376 [PubMed - indexed for MEDLINE]

Mass balance and metabolism of the antimalarial pyronaridine in healthy volunteers.

Wed, 16/09/2015 - 13:44
Related Articles Mass balance and metabolism of the antimalarial pyronaridine in healthy volunteers. Eur J Drug Metab Pharmacokinet. 2015 Mar;40(1):75-86 Authors: Morris CA, Dueker SR, Lohstroh PN, Wang LQ, Fang XP, Jung D, Lopez-Lazaro L, Baker M, Duparc S, Borghini-Fuhrer I, Pokorny R, Shin JS, Fleckenstein L Abstract This was a single dose mass balance and metabolite characterization study of the antimalarial agent pyronaridine. Six healthy male adults were administered a single oral dose of 720 mg pyronaridine tetraphosphate with 800 nCi of radiolabeled (14)C-pyronaridine. Urine and feces were continuously collected through 168 h post-dose, with intermittent 48 h collection periods thereafter through 2064 h post-dose. Drug recovery was computed for analyzed samples and interpolated for intervening time periods in which collection did not occur. Blood samples were obtained to evaluate the pharmacokinetics of total radioactivity and of the parent compound. Total radioactivity in urine, feces, and blood samples was determined by accelerator mass spectrometry (AMS); parent concentrations in blood were determined with LC/MS. Metabolite identification based on blood, urine, and feces samples was conducted using a combination of LC + AMS for identifying radiopeaks, followed by LC/MS/MS for identity confirmation/elucidation. The mean cumulative drug recovery in the urine and feces was 23.7 and 47.8 %, respectively, with an average total recovery of 71.5 %. Total radioactivity was slowly eliminated from blood, with a mean half-life of 33.5 days, substantially longer than the mean parent compound half-life of 5.03 days. Total radioactivity remained detectable in urine and feces collected in the final sampling period, suggesting ongoing elimination. Nine primary and four secondary metabolites of pyronaridine were identified. This study revealed that pyronaridine and its metabolites are eliminated by both the urinary and fecal routes over an extended period of time, and that multiple, varied pathways characterize pyronaridine metabolism. PMID: 24590312 [PubMed - indexed for MEDLINE]

metabolomics; +25 new citations

Tue, 15/09/2015 - 12:09
25 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 2015/09/15PubMed 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.

A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction.

Mon, 14/09/2015 - 13:45
A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction. Vet J. 2015 Aug 4; Authors: Medina-Torres CE, van Eps AW, Nielsen LK, Hodson MP Abstract Lamellar bioenergetic failure is thought to contribute to laminitis pathogenesis but current knowledge of lamellar bioenergetic physiology is limited. Metabolomic analysis (MA) can systematically profile multiple metabolites. Applied to lamellar microdialysis samples (dialysate), lamellar bioenergetic changes during laminitis (the laminitis metabolome) can be characterised. The objectives of this study were to develop a technique for targeted MA of lamellar and skin dialysates in normal horses, and to compare the lamellar and plasma metabolomic profiles of normal horses with those from horses developing experimentally induced laminitis. Archived lamellar and skin dialysates (n = 7) and tissues (n = 6) from normal horses, and lamellar dialysate and plasma from horses given either 10 g/kg oligofructose (treatment group, OFT; n = 4) or sham (control group, CON; n = 4) were analysed. The concentrations of 44 intermediates of central carbon metabolism (CCM) were determined using liquid chromatography-tandem mass spectrometry. Data were analysed using multivariate (MVA) and univariate (UVA) analysis methods. The plasma metabolome appeared to be more variable than the lamellar metabolome by MVA, driven by malate, pyruvate, aconitate and glycolate. In lamellar dialysate, these metabolites decreased in OFT horses at the later time points. Plasma malate was markedly increased after 6 h in OFT horses. Plasma malate concentrations between OFT and CON at this time point were significantly different by UVA. MA of lamellar CCM was capable of differentiating horses developing experimental laminitis from controls. Lamellar malate, pyruvate, aconitate and glycolate, and plasma malate alone were identified as the source of differentiation between OFT and CON groups. These results highlighted clear discriminators between OFT and CON horses, suggesting that changes in energy metabolism occur locally in the lamellar tissue during laminitis development. The biological significance of these alterations requires further investigation. PMID: 26364239 [PubMed - as supplied by publisher]

Metabolomics of Disease Resistance in Crops.

Mon, 14/09/2015 - 13:45
Metabolomics of Disease Resistance in Crops. Curr Issues Mol Biol. 2015 Sep 11;19:13-30 Authors: Arbona V, Gómez-Cadenas A Abstract Plants are continuously exposed to the attack of invasive microorganisms, such as fungi or bacteria, and also viruses. To fight these attackers, plants develop different metabolic and genetic responses whose final outcome is the production of either toxic compounds that kill the pathogen or deter its growth, and/or semiotic molecules that alert other individuals from the same plant species. These molecules are derived from the secondary metabolism and their production is induced upon detection of a pathogen-associated molecular pattern (PAMP). These PAMPs are different molecules that are perceived by the host cell triggering defense responses. PAMP-elicited compounds are highly diverse and specific of every plant species and can be divided into preformed metabolites or phytoanticipins that are converted into toxic molecules upon pathogen perception, and toxic metabolites or phytoalexins that are produced only upon pathogen attack. Moreover, plant volatile emissions are also modified in response to pathogen attack to alert neighboring individuals or to make plants less attractive to pathogen vector arthropods. Plant metabolite profiling techniques have allowed the identification of novel antimicrobial molecules that are induced upon elicitation. However, more studies are required to assess the specific function of metabolites or metabolite blends on plant-microbe interactions. PMID: 26364233 [PubMed - as supplied by publisher]

Metabolomic approach to profile functional and metabolic changes in heart failure.

Mon, 14/09/2015 - 13:45
Metabolomic approach to profile functional and metabolic changes in heart failure. J Transl Med. 2015;13(1):297 Authors: Deidda M, Piras C, Dessalvi CC, Locci E, Barberini L, Torri F, Ascedu F, Atzori L, Mercuro G Abstract BACKGROUND: Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. METHODS: A 500 MHz proton nuclear magnetic resonance ((1)H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 ± 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 ± 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. RESULTS: OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R(2) [R(2)(X) = 0.64; R(2)(Y) = 0.59] and Q(2) (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. CONCLUSIONS: The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function. PMID: 26364058 [PubMed - as supplied by publisher]

OMICS in Plant Disease Resistance.

Mon, 14/09/2015 - 13:45
OMICS in Plant Disease Resistance. Curr Issues Mol Biol. 2015 Sep 11;19:1-2 Authors: Bhadauria V Abstract The term OMICS, which look into the global profiling and analysis of various cellular molecules, has gained new heights with the advancement of next-generation sequencing and mass spectrometry technologies. It has broader implication in genetic improvement of crops for resistance against various diseases of economic significance. This focus issue entitled OMICS in Plant Disease Resistance highlights the implication of OMICS (genomics, transcriptomics, proteomics and metabolomics) in agricultural research. PMID: 26363815 [PubMed - as supplied by publisher]

Omics Approach to Identify Factors Involved in Brassica Disease Resistance.

Mon, 14/09/2015 - 13:45
Omics Approach to Identify Factors Involved in Brassica Disease Resistance. Curr Issues Mol Biol. 2015 Sep 11;19:31-42 Authors: Francisco M, Soengas P, Velasco P, Bhadauria V, Cartea ME, Rodríguez VM Abstract Understanding plant's defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various 'omics' technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in 'omic' tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance. PMID: 26363709 [PubMed - as supplied by publisher]

Omics Approaches for the Engineering of Pathogen Resistant Plants.

Mon, 14/09/2015 - 13:45
Omics Approaches for the Engineering of Pathogen Resistant Plants. Curr Issues Mol Biol. 2015 Sep 11;19:89-98 Authors: Gomez-Casati DF, Pagani MA, Busi MV, Bhadauria V Abstract The attack of different pathogens, such as bacteria, fungi and viruses has a negative impact on crop production. In counter such attacks, plants have developed different strategies involving the modification of gene expression, activation of several metabolic pathways and post-translational modification of proteins, which culminate into the accumulation of primary and secondary metabolites implicated in plant defense responses. The recent advancement in omics techniques allows the increase coverage of plants transcriptomes, proteomes and metabolomes during pathogen attack, and the modulation of the response after the infection. Omics techniques also allow us to learn more about the biological cycle of the pathogens in addition to the identification of novel virulence factors in pathogens and their host targets. Both approaches become important to decipher the mechanism underlying pathogen attacks and to develop strategies for improving disease-resistant plants. In this review, we summarize some of the contribution of genomics, transcriptomics, proteomics, metabolomics and metallomics in devising the strategies to obtain plants with increased resistance to pathogens. These approaches constitute important research tools in the development of new technologies for the protection against diseases and increase plant production. PMID: 26363625 [PubMed - as supplied by publisher]

[¹H NMR metabonomics study of pancreatic extracts from insulin-resistant rats induced by fructose feeding].

Mon, 14/09/2015 - 13:45
Related Articles [¹H NMR metabonomics study of pancreatic extracts from insulin-resistant rats induced by fructose feeding]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Aug;34(9):1301-4 Authors: Wang L, Zheng L, Zhang L, Chen A, Qiu C, Xu J, Yang Y Abstract OBJECTIVE: To study the metabolic changes of pancreatic extracts from insulin-resistant rats induced by fructose feeding using nuclear magnetic resonance ¹H spectroscopy (¹H NMR). METHODS: Sixteen Wistar rats were divided equally into control group and model group and given water and 10% fructose water for 8 weeks, respectively. The pancreatic tissues were then obtained for H NMR spectra analysis and principal component analysis (PCA). RESULTS: Compared with the control rats, the rats in the model group showed significantly increased creatine, betaine/TMAO, taurine, glycine and myo-inositol and decreased levels of lipids, lactate, glutamate, choline and GPC/PC. CONCLUSION: ¹H NMR and pattern recognition can define the metabolic characteristics of the pancreatic tissue extracts from insulin-resistant rats and provide reliable metabolic evidence for studying the mechanisms of insulin resistance at the molecular level. PMID: 25263363 [PubMed - indexed for MEDLINE]

[Determination of serum carbamazepine concentration and metabonomic analysis in rats].

Mon, 14/09/2015 - 13:45
Related Articles [Determination of serum carbamazepine concentration and metabonomic analysis in rats]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Jun;34(7):1025-9 Authors: Cai Z, Mo LQ, Guan SY, Liu CY, Liu Y, Guo D Abstract OBJECTIVE: To study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy. METHODS: Twenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. ¹H nuclear magnetic resonance (¹H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were also examined. RESULTS: Steady-state blood concentration of carbamazepine in high-, medium- and low-dose groups were 14.64 ± 1.41, 8.54 ± 1.19, and 4.56 ± 0.64 µg/ml, respectively. Slight liver swelling was found in high-dose group, but none of the groups showed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serum concentrations of 1,3-diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine, L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treated groups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although the concentrations of the metabolites varied between the carbamazepine groups. CONCLUSIONS: Carbamazepine significantly affects metabolism in normal rats. This finding provides evidence for clinical drug monitoring and drug safety of carbamazepine. NMR technique has important values for pharmacodynamic and toxicological evaluation of drugs. PMID: 25057077 [PubMed - indexed for MEDLINE]

Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches.

Sun, 13/09/2015 - 13:04
Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches. Chemosphere. 2015 Sep 9;144:214-224 Authors: Song Q, Chen H, Li Y, Zhou H, Han Q, Diao X Abstract Benzo(a)pyrene (BaP) and dichlorodiphenyltrichloroethane (DDT) are persistent organic pollutants and environmental estrogens (EEs) with known toxicity towards the green mussel, Perna viridis. In this study, the toxic effects of BaP (10 μg/L) and DDT (10 μg/L) and their mixture were assessed in green mussel gills with proteomic and metabolomic approaches. Metabolic responses indicated that BaP mainly caused disturbance in osmotic regulation by significantly decrease in branched chain amino acids, dimethylamine and dimethylglycine in gills of male green mussels after exposure for 7 days. DDT mainly caused disturbance in osmotic regulation and energy metabolism by differential alteration of betaine, dimethylamine, dimethylglycine, amino acids, and succinate in gills of male green mussels. However, the mixture of BaP and DDT didn't show obvious metabolite changes. Proteomic analysis showed different protein expression profiles between different treatment groups, which demonstrated that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced cell apoptosis, disturbance in protein digestion and energy metabolism in gills of green mussels, whereas DDT exposure altered proteins that were associated with oxidative stress, cytoskeleton and cell structure, protein digestion and energy metabolism. However, the mixture of BaP and DDT affected proteins related to the oxidative stress, cytoskeleton and cell structure, protein biosynthesis and modification, energy metabolism, growth and apoptosis. PMID: 26363323 [PubMed - as supplied by publisher]

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