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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 15 min 8 sec ago

GC-MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows.

Fri, 18/05/2018 - 14:46
Related Articles GC-MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows. Metabolomics. 2018;14(5):67 Authors: Xue F, Pan X, Jiang L, Guo Y, Xiong B Abstract Introduction: Thiamine is known to attenuate high-concentrate diet induced subacute ruminal acidosis (SARA) in dairy cows, however, the underlying mechanisms remain unclear. Objectives: The major objective of this study was to investigate the metabolic mechanisms of thiamine supplementation on high-concentrate diet induced SARA. Methods: Six multiparous, rumen-fistulated Holstein cows were used in a replicated 3 × 3 Latin square design. The treatments included a control diet (CON; 20% starch, dry matter basis), a SARA-inducing diet (SAID; 33.2% starch, dry matter basis) and SARA-inducing diet supplemented with 180 mg of thiamine/kg of dry matter intake (SAID + T). On d21 of each period, ruminal fluid samples were collected at 3 h post feeding, and GC/MS was used to analyze rumen fluid samples. Results: PCA and OPLS-DA analysis demonstrated that the ruminal metabolite profile were different in three treatments. Compared with CON treatment, SAID feeding significantly decreased rumen pH, acetate, succinic acid, increased propionate, pyruvate, lactate, glycine and biogenic amines including spermidine and putrescine. Thiamine supplementation significantly decreased rumen content of propionate, pyruvate, lactate, glycine and spermidine; increase rumen pH, acetate and some medium-chain fatty acids. The enrichment analysis of different metabolites indicated that thiamine supplementation mainly affected carbohydrates, amino acids, pyruvate and thiamine metabolism compared with SAID treatment. Conclusions: These findings revealed that thiamine supplementation could attenuate high-concentrate diet induced SARA by increasing pyruvate formate-lyase activity to promote pyruvate to generate acetyl-CoA and inhibit lactate generation. Besides, thiamine reduced biogenic amines to alleviate ruminal epithelial inflammatory response. PMID: 29770108 [PubMed]

Metabolomic profile of systemic sclerosis patients.

Fri, 18/05/2018 - 14:46
Related Articles Metabolomic profile of systemic sclerosis patients. Sci Rep. 2018 May 16;8(1):7626 Authors: Murgia F, Svegliati S, Poddighe S, Lussu M, Manzin A, Spadoni T, Fischetti C, Gabrielli A, Atzori L Abstract Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726-0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7-0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease. PMID: 29769578 [PubMed - in process]

PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice.

Fri, 18/05/2018 - 14:46
Related Articles PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice. Drug Metab Dispos. 2018 May 16;: Authors: Li CY, Dempsey JL, Wang D, Lee S, Weigel KM, Fei Q, Bhatt DK, Prasad B, Raftery D, Gu H, Cui JY Abstract Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well-characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 μmol/kg), or BDE-99 (100 μmol/kg) once daily for 4-days (n=3-5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichacea Allobaculum spp., which have been reported to have anti-inflammatory and anti-obesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple bio-compartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7α-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs down-regulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modifying the "gut-liver axis". PMID: 29769268 [PubMed - as supplied by publisher]

Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters.

Fri, 18/05/2018 - 14:46
Related Articles Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters. Chemosphere. 2018 Apr;197:7-13 Authors: Du Z, Cao YF, Li SN, Hu CM, Fu ZW, Huang CT, Sun XY, Liu YZ, Yang K, Fang ZZ Abstract Phthalate monoesters are important metabolites of phthalate esters (PAEs) which have been extensively utilized in industry. This study aims to investigate the inhibition of phthalate monoesters on the activity of various isoforms of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of environmental endocrine disruptors from the new perspectives. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human UGT isoforms. 100 μM phthalate monoesters exhibited negligible inhibition towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7, UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate (MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition towards UGT1A9. The inhibition kinetic parameters (Ki) were calculated to be 11.25 μM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 μM for MBZP-UGT1A9, MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking indicated that both hydrogen bonds formation and hydrophobic interactions significantly contributed to the interaction between phthalate monoesters and UGT isoforms. All these information will be beneficial for understanding the adverse effects of PAEs. PMID: 29328989 [PubMed - indexed for MEDLINE]

[Metabonomics on toxicity reduction of Glycyrrhizae Radix et Rhizoma for Aconiti Lateralis Radix Preparata in Sini Tang].

Fri, 18/05/2018 - 14:46
Related Articles [Metabonomics on toxicity reduction of Glycyrrhizae Radix et Rhizoma for Aconiti Lateralis Radix Preparata in Sini Tang]. Zhongguo Zhong Yao Za Zhi. 2016 Apr;41(8):1523-1529 Authors: Li Y, Fu CM, Peng W, Li B, Fu S, Zhang HM Abstract To analyze the endogenous metabolite changes in rat plasma after intervention by Sini Tang and Sini Tang without Glycyrrhizae Radix et Rhizoma based on GC-MS metabonomics technology, and study the toxicity reduction effect of Glycyrrhizae Radix et Rhizoma in Sini Tang on Aconiti Lateralis Radix Preparata. Eighteen SD rats were randomly divided into normal group, Sini Tang group and Sini Tang without Glycyrrhizae Radix et Rhizoma group on average. The rats in Sini Tang group and Sini Tang without Glycyrrhizae Radix et Rhizoma group were treated respectively with physic liquor by intragastric administration at the dose of 0.02 mL•g ⁻¹ (equivalent to 0.8 g•mL ⁻¹ crude drugs) once a day for 7 days. The rats in normal group were given with equal volume of saline solution. The plasma samples were collected from each rat 0.5 h after the last administration for GC-MS detection. The data was used for multivariate statistical analysis to obtain 14 potential metabolic markers(13 of them were identified). Then their relative content and metabolic pathways were analyzed. Compared with Sini Tang without Glycyrrhizae Radix et Rhizoma group, seven metabolic markers of were reduced in Sini Tang group. Analysis on physiological functions of these potential metabolic markers showed that the Glycyrrhizae Radix et Rhizoma in Sini Tang could reduce the toxicity of Aconiti Lateralis Radix Preparata by adjusting the glycolysis, lipid metabolism, citrate cycle and some amino acids metabolism. PMID: 28884550 [PubMed - indexed for MEDLINE]

Integrative omics to detect bacteremia in patients with febrile neutropenia.

Thu, 17/05/2018 - 14:25
Integrative omics to detect bacteremia in patients with febrile neutropenia. PLoS One. 2018;13(5):e0197049 Authors: Kelly RS, Lasky-Su J, Yeung SJ, Stone RM, Caterino JM, Hagan SC, Lyman GH, Baden LR, Glotzbecker BE, Coyne CJ, Baugh CW, Pallin DJ Abstract BACKGROUND: Cancer chemotherapy-associated febrile neutropenia (FN) is a common condition that is deadly when bacteremia is present. Detection of bacteremia depends on culture, which takes days, and no accurate predictive tools applicable to the initial evaluation are available. We utilized metabolomics and transcriptomics to develop multivariable predictors of bacteremia among FN patients. METHODS: We classified emergency department patients with FN and no apparent infection at presentation as bacteremic (cases) or not (controls), according to blood culture results. We assessed relative metabolite abundance in plasma, and relative expression of 2,560 immunology and cancer-related genes in whole blood. We used logistic regression to identify multivariable predictors of bacteremia, and report test characteristics of the derived predictors. RESULTS: For metabolomics, 14 bacteremic cases and 25 non-bacteremic controls were available for analysis; for transcriptomics we had 7 and 22 respectively. A 5-predictor metabolomic model had an area under the receiver operating characteristic curve of 0.991 (95%CI: 0.972,1.000), 100% sensitivity, and 96% specificity for identifying bacteremia. Pregnenolone steroids were more abundant in cases and carnitine metabolites were more abundant in controls. A 3-predictor gene expression model had corresponding results of 0.961 (95%CI: 0.896,1.000), 100%, and 86%. Genes involved in innate immunity were differentially expressed. CONCLUSIONS: Classifiers derived from metabolomic and gene expression data hold promise as objective and accurate predictors of bacteremia among FN patients without apparent infection at presentation, and can provide insights into the underlying biology. Our findings should be considered illustrative, but may lay the groundwork for future biomarker development. PMID: 29768470 [PubMed - in process]

Untargeted Metabolomics Identifies Novel Potential Biomarkers of Habitual Food Intake in a Cross-Sectional Study of Postmenopausal Women.

Thu, 17/05/2018 - 14:25
Untargeted Metabolomics Identifies Novel Potential Biomarkers of Habitual Food Intake in a Cross-Sectional Study of Postmenopausal Women. J Nutr. 2018 May 15;: Authors: Wang Y, Gapstur SM, Carter BD, Hartman TJ, Stevens VL, Gaudet MM, McCullough ML Abstract Background: Recent studies suggest that untargeted metabolomics is a promising tool to identify novel biomarkers of individual foods. However, few large cross-sectional studies with comprehensive data on habitual diet and circulating metabolites have been conducted. Objective: We aimed to identify potential food biomarkers and evaluate their predictive accuracy. Methods: We conducted a cross-sectional analysis of consumption of 91 food groups or items, assessed by a 152-item food-frequency questionnaire, in relation to 1186 serum metabolites measured by mass spectrometry-based platforms from 1369 nonsmoking postmenopausal women (mean age = 68.3 y). Diet-metabolite associations were selected by Pearson's partial correlation analysis (P < 4.63 × 10-7, |r| > 0.2). The predictive accuracy of the selected food metabolites was evaluated from the area under the curve (AUC) calculated from receiver operating characteristic analysis conducted among women in the top and bottom quintiles of dietary intake. Results: We identified 379 diet-metabolite associations. Forty-two food groups or items were correlated with 199 serum metabolites. We replicated 63 metabolites as biomarkers of habitual food intake reported in previous cross-sectional studies. Among those not previously shown to be associated with habitual diet, several are biologically plausible and were reported in acute feeding studies including: banana and dopamine 3-O-sulfate (r = 0.34, AUC = 76%) and dopamine 4-O-sulfate (r = 0.33, AUC = 74%), garlic and alliin (r = 0.24, AUC = 69%), N-acetylalliin (r = 0.27, AUC = 70%), and S-allylcysteine (r = 0.23, AUC = 69). Two unannotated metabolites were the strongest predictors for dark fish (X-02269, r = 0.51, AUC = 94%) and coffee intake (X-21442, r = 0.62, AUC = 98%). Conclusions: In this comprehensive, cross-sectional analysis of habitual food intake and serum metabolites among postmenopausal women, we identified several potentially novel food biomarkers and replicated others. Our findings contribute to the limited literature on food-based biomarkers and highlight the significant and promising role that large cohort studies with archived blood samples could play in this field. This study was registered at clinicaltrials.gov as NCT03282812. PMID: 29767735 [PubMed - as supplied by publisher]

Metabolomics: a high-throughput screen for biochemical and bioactivity diversity in plants and crops.

Thu, 17/05/2018 - 14:25
Metabolomics: a high-throughput screen for biochemical and bioactivity diversity in plants and crops. Curr Pharm Des. 2018 May 15;: Authors: Foito A, Stewart D Abstract Plants and crops contain a staggering diversity of compounds, many of which have pharmacological activity towards a variety of diseases. These properties have been exploited by traditional and modern medicine providing important sources of healthcare to this day. The contribution of natural products (such as plant-derived) to the modern pharmacopeia is indeed significant; however, the process of identifying novel bioactive compounds from biological sources has been a central challenge in the discovery of natural products. The resolution of these challenges relied extensively on the use of hyphenated mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based analytical technologies for the structural elucidation and annotation of novel compounds. Technical developments in instrumentation and data processing have fostered the development of the field of metabolomics which provides a wealth of tools with the huge potential for application in the process of drug/bioactive discovery from plant tissues. This manuscript provides an overview of the metabolomics toolbox available for the discovery of novel bioactive compounds and the integration of these tools in the bioprospection and drug discovery workflows. PMID: 29766789 [PubMed - as supplied by publisher]

Soft Biomaterial-based nanocrystal in pharmaceutical.

Thu, 17/05/2018 - 14:25
Soft Biomaterial-based nanocrystal in pharmaceutical. Curr Pharm Des. 2018 May 15;: Authors: Chen N, Su T, Cheng Z, An F Abstract BACKGROUND AND OBJECTIVE: Bio-soft material, a class of derivatives of the natural or synthetic material, is getting more and more prevalent in biomedical researches and applications due to the advantages such as in-vivo biodegradation, good water solubility and designable targeting ability. With the presence of bio-soft materials, the drug nanocrystal can be easily generated and aggregated in a feasible process. Given the promising application of the bio-soft material in biological and chemical research, it is valuable to discuss the crucial step in designing bio-soft materials and analyze the emerging properties of bio-soft materials. METHODS: A comprehensive literature survey in the field of bio-soft material development and analysis has been conducted. The collected data and figures were meticulously analyzed and interpreted. RESULTS: In this review, the details of bio-soft materials based nanocrystal were demonstrated in three sections with respect to different materials. In each section, the pros and cons for each bio-soft material and its derivatives were elaborately listed and discussed. CONCLUSION: The review enables an insightful discussion about the properties and the applications of existing bio-soft material. It may contribute to the further researches about bio-soft material development and analysis. PMID: 29766780 [PubMed - as supplied by publisher]

Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats.

Thu, 17/05/2018 - 14:25
Related Articles Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats. J Physiol Biochem. 2018 May 15;: Authors: Mediani A, Abas F, Maulidiani M, Abu Bakar Sajak A, Khatib A, Tan CP, Ismail IS, Shaari K, Ismail A, Lajis NH Abstract Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (1H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated. The obese-diabetic model was developed by feeding the rats a high-fat diet and inducing diabetic conditions with a low dose of streptozotocin (STZ) (25 mg/kg bw). However, the normal rats were induced by a high dose of STZ (55 mg/kg bw). A partial least squares discriminant analysis (PLS-DA) model showed the biomarkers of both DM types compared to control. The synthesis and degradation of ketone bodies, tricarboxylic (TCA) cycles, and amino acid pathways were the ones most involved in the variation with the highest impact. The diabetic groups also exhibited a noticeable increase in the plasma glucose level and lipid profile disorders compared to the control. There was also an increase in the plasma cholesterol and low-density lipoprotein (LDL) levels and a decline in the high-density lipoprotein (HDL) of diabetic rats. The normal-diabetic rats exhibited the highest effect of all parameters compared to the obese-diabetic rats in the advancement of the DM period. This finding can build a platform to understand the metabolic and biochemical complications of both types of DM and can generate ideas for finding targeted drugs. PMID: 29766441 [PubMed - as supplied by publisher]

Consensus guidelines for the use and interpretation of angiogenesis assays.

Thu, 17/05/2018 - 14:25
Related Articles Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis. 2018 May 15;: Authors: Nowak-Sliwinska P, Alitalo K, Allen E, Anisimov A, Aplin AC, Auerbach R, Augustin HG, Bates DO, van Beijnum JR, Bender RHF, Bergers G, Bikfalvi A, Bischoff J, Böck BC, Brooks PC, Bussolino F, Cakir B, Carmeliet P, Castranova D, Cimpean AM, Cleaver O, Coukos G, Davis GE, De Palma M, Dimberg A, Dings RPM, Djonov V, Dudley AC, Dufton NP, Fendt SM, Ferrara N, Fruttiger M, Fukumura D, Ghesquière B, Gong Y, Griffin RJ, Harris AL, Hughes CCW, Hultgren NW, Iruela-Arispe ML, Irving M, Jain RK, Kalluri R, Kalucka J, Kerbel RS, Kitajewski J, Klaassen I, Kleinmann HK, Koolwijk P, Kuczynski E, Kwak BR, Marien K, Melero-Martin JM, Munn LL, Nicosia RF, Noel A, Nurro J, Olsson AK, Petrova TV, Pietras K, Pili R, Pollard JW, Post MJ, Quax PHA, Rabinovich GA, Raica M, Randi AM, Ribatti D, Ruegg C, Schlingemann RO, Schulte-Merker S, Smith LEH, Song JW, Stacker SA, Stalin J, Stratman AN, Van de Velde M, van Hinsbergh VWM, Vermeulen PB, Waltenberger J, Weinstein BM, Xin H, Yetkin-Arik B, Yla-Herttuala S, Yoder MC, Griffioen AW Abstract The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference. PMID: 29766399 [PubMed - as supplied by publisher]

RDFIO: extending Semantic MediaWiki for interoperable biomedical data management.

Thu, 17/05/2018 - 14:25
Related Articles RDFIO: extending Semantic MediaWiki for interoperable biomedical data management. J Biomed Semantics. 2017 Sep 04;8(1):35 Authors: Lampa S, Willighagen E, Kohonen P, King A, Vrandečić D, Grafström R, Spjuth O Abstract BACKGROUND: Biological sciences are characterised not only by an increasing amount but also the extreme complexity of its data. This stresses the need for efficient ways of integrating these data in a coherent description of biological systems. In many cases, biological data needs organization before integration. This is not seldom a collaborative effort, and it is thus important that tools for data integration support a collaborative way of working. Wiki systems with support for structured semantic data authoring, such as Semantic MediaWiki, provide a powerful solution for collaborative editing of data combined with machine-readability, so that data can be handled in an automated fashion in any downstream analyses. Semantic MediaWiki lacks a built-in data import function though, which hinders efficient round-tripping of data between interoperable Semantic Web formats such as RDF and the internal wiki format. RESULTS: To solve this deficiency, the RDFIO suite of tools is presented, which supports importing of RDF data into Semantic MediaWiki, with metadata needed to export it again in the same RDF format, or ontology. Additionally, the new functionality enables mash-ups of automated data imports combined with manually created data presentations. The application of the suite of tools is demonstrated by importing drug discovery related data about rare diseases from Orphanet and acid dissociation constants from Wikidata. The RDFIO suite of tools is freely available for download via pharmb.io/project/rdfio . CONCLUSIONS: Through a set of biomedical demonstrators, it is demonstrated how the new functionality enables a number of usage scenarios where the interoperability of SMW and the wider Semantic Web is leveraged for biomedical data sets, to create an easy to use and flexible platform for exploring and working with biomedical data. PMID: 28870259 [PubMed - indexed for MEDLINE]

Interest of metabonomic approach in environmental nephrotoxicants: Application to aristolochic acid exposure.

Thu, 17/05/2018 - 14:25
Related Articles Interest of metabonomic approach in environmental nephrotoxicants: Application to aristolochic acid exposure. Food Chem Toxicol. 2017 Oct;108(Pt A):19-29 Authors: Duquesne M, Declèves AE, De Prez E, Nortier J, Colet JM PMID: 28694082 [PubMed - indexed for MEDLINE]

Mass Spectrometry Imaging, Laser Capture Microdissection, and LC-MS/MS of the Same Tissue Section.

Thu, 17/05/2018 - 14:25
Related Articles Mass Spectrometry Imaging, Laser Capture Microdissection, and LC-MS/MS of the Same Tissue Section. J Proteome Res. 2017 Aug 04;16(8):2993-3001 Authors: Dilillo M, Pellegrini D, Ait-Belkacem R, de Graaf EL, Caleo M, McDonnell LA Abstract Mass spectrometry imaging (MSI) is able to simultaneously record the distributions of hundreds of molecules directly from tissue. Rapid direct tissue analysis is essential for MSI in order to maintain spatial localization and acceptable measurement times. The absence of an explicit analyte separation/purification step means MSI lacks the depth of coverage of LC-MS/MS. In this work, we demonstrate how atmospheric pressure MALDI-MSI enables the same tissue section to be first analyzed by MSI, to identify regions of interest that exhibit distinct molecular signatures, followed by localized proteomics analysis using laser capture microdissection isolation and LC-MS/MS. PMID: 28648079 [PubMed - indexed for MEDLINE]

Integrative Analysis of Renal Ischemia/Reperfusion Injury and Remote Ischemic Preconditioning in Mice.

Thu, 17/05/2018 - 14:25
Related Articles Integrative Analysis of Renal Ischemia/Reperfusion Injury and Remote Ischemic Preconditioning in Mice. J Proteome Res. 2017 Aug 04;16(8):2877-2886 Authors: Cho K, Min SI, Ahn S, Min SK, Ahn C, Yu KS, Jang IJ, Cho JY, Ha J Abstract Remote ischemic preconditioning (RIPC) is a strategy to induce resistance in a target organ against the oxidative stress and injury caused by ischemia and reperfusion (IR). RIPC harnesses the body's endogenous protective capabilities through brief episodes of IR applied in organs remote from the target. Few studies have analyzed this phenomenon in the kidney. Furthermore, the window of protection representing RIPC efficacy has not been fully elucidated. Here, we performed a multiomics study to specify those associated with protective effects of RIPC against the IR injury. A total of 30 mice were divided to four groups: sham, IR only, late RIPC + IR, and early RIPC + IR. We found that IR clearly led to tubular injury, whereas both preconditioning groups exhibited attenuated injury after the insult. In addition, renal IR injury produced changes of the metabolome in kidney, serum, and urine specimens. Furthermore, distinctive mRNA and associated protein expression changes supported potential mechanisms. Our findings revealed that RIPC effectively reduces renal damage after IR and that the potential mechanisms differed between the two time windows of protection. These results may potentially be extended to humans to allow non- or minimally invasive diagnosis of renal IR injury and RIPC efficacy. PMID: 28627174 [PubMed - indexed for MEDLINE]

Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

Thu, 17/05/2018 - 14:25
Related Articles Metabolome analysis of effect of aspirin on Drosophila lifespan extension. Exp Gerontol. 2017 Sep;95:54-62 Authors: Song C, Zhu C, Wu Q, Qi J, Gao Y, Zhang Z, Gaur U, Yang D, Fan X, Yang M Abstract Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. PMID: 28457986 [PubMed - indexed for MEDLINE]

Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis.

Thu, 17/05/2018 - 14:25
Related Articles Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis. Clin Transl Sci. 2017 Jul;10(4):292-301 Authors: Roda A, Aldini R, Camborata C, Spinozzi S, Franco P, Cont M, D'Errico A, Vasuri F, Degiovanni A, Maroni L, Adorini L Abstract Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride-induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal clearance were lower than in controls. BAs' qualitative and quantitative compositions were not modified by a single administration of OCA. In all the matrices studied, OCA concentrations were significantly lower than those of endogenous BAs, potentially much more cytotoxic. PMID: 28411380 [PubMed - indexed for MEDLINE]

metabolomics; +46 new citations

Wed, 16/05/2018 - 14:05
46 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 2018/05/16PubMed comprises more than millions of 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.

metabolomics; +18 new citations

Tue, 15/05/2018 - 16:47
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 2018/05/15PubMed comprises more than millions of 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.

metabolomics; +18 new citations

Tue, 15/05/2018 - 13:43
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 2018/05/15PubMed comprises more than millions of 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.

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