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: 1 hour 2 min ago

metabolomics; +22 new citations

Wed, 09/01/2019 - 16:12
22 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 2019/01/09PubMed 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; +22 new citations

Wed, 09/01/2019 - 13:09
22 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 2019/01/09PubMed 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; +19 new citations

Tue, 08/01/2019 - 15:43
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/01/08PubMed 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; +19 new citations

Tue, 08/01/2019 - 12:43
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/01/08PubMed 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.

BioTransformer: a comprehensive computational tool for small molecule metabolism prediction and metabolite identification.

Mon, 07/01/2019 - 12:28
BioTransformer: a comprehensive computational tool for small molecule metabolism prediction and metabolite identification. J Cheminform. 2019 Jan 05;11(1):2 Authors: Djoumbou-Feunang Y, Fiamoncini J, Gil-de-la-Fuente A, Greiner R, Manach C, Wishart DS Abstract BACKGROUND: A number of computational tools for metabolism prediction have been developed over the last 20 years to predict the structures of small molecules undergoing biological transformation or environmental degradation. These tools were largely developed to facilitate absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, although there is now a growing interest in using such tools to facilitate metabolomics and exposomics studies. However, their use and widespread adoption is still hampered by several factors, including their limited scope, breath of coverage, availability, and performance. RESULTS: To address these limitations, we have developed BioTransformer, a freely available software package for accurate, rapid, and comprehensive in silico metabolism prediction and compound identification. BioTransformer combines a machine learning approach with a knowledge-based approach to predict small molecule metabolism in human tissues (e.g. liver tissue), the human gut as well as the environment (soil and water microbiota), via its metabolism prediction tool. A comprehensive evaluation of BioTransformer showed that it was able to outperform two state-of-the-art commercially available tools (Meteor Nexus and ADMET Predictor), with precision and recall values up to 7 times better than those obtained for Meteor Nexus or ADMET Predictor on the same sets of pharmaceuticals, pesticides, phytochemicals or endobiotics under similar or identical constraints. Furthermore BioTransformer was able to reproduce 100% of the transformations and metabolites predicted by the EAWAG pathway prediction system. Using mass spectrometry data obtained from a rat experimental study with epicatechin supplementation, BioTransformer was also able to correctly identify 39 previously reported epicatechin metabolites via its metabolism identification tool, and suggest 28 potential metabolites, 17 of which matched nine monoisotopic masses for which no evidence of a previous report could be found. CONCLUSION: BioTransformer can be used as an open access command-line tool, or a software library. It is freely available at https://bitbucket.org/djoumbou/biotransformerjar/ . Moreover, it is also freely available as an open access RESTful application at www.biotransformer.ca , which allows users to manually or programmatically submit queries, and retrieve metabolism predictions or compound identification data. PMID: 30612223 [PubMed]

Vitamin C for the critically ill: Is the evidence strong enough?

Mon, 07/01/2019 - 12:28
Vitamin C for the critically ill: Is the evidence strong enough? Nutrition. 2018 Oct 22;60:185-190 Authors: L Langlois P, Lamontagne F Abstract Vitamin C exhibits interesting properties in the context of critical illness, with benefits described in neurologic, cardiovascular, renal, and hematologic systems, both in in vitro and in animal models. Through direct effects on bacterial replication, immunomodulation, and antioxidant reserve of the organism, vitamin C directly affects the pathophysiological process of sepsis, trauma, burn, and systemic inflammation. Even if several observational trials have linked vitamin C deficiency to worse outcomes, the evidence is not such as to provide us with a distinction between causality effects or simple epiphenomenon, and the current focus is on interventional trials. Pharmacokinetic data suggest that a minimal supplementation of 3 g/d intravenously is required to restore normal serum values in critically ill patients with known deficiency. According to these data, only five trials, including a retrospective analysis, studied pharmacologic dose: three as an antioxidant cocktail and two as monotherapy. The largest trial, conducted in 2002, reported reduced incidence of multiorgan failure and duration of mechanical ventilation. Recently a retrospective analysis reported impressive results after administration of vitamin C, thiamine, and hydrocortisone. The two most recent trials reported improved clinical outcomes, including improved mortality, but contained significant methodological limitations. A recent systematic review did not find clinical benefits with the most-studied low-dose oral supplementation, potentially because of suboptimal or insufficient repletion. Current guidelines do not support the administration of high-dose vitamin C in critically ill patients. Future larger trials are required to support any therapy, but the low cost and safety profile can justify supplementation in the meantime. Metabolomics study will further help understand biological effect. PMID: 30612038 [PubMed - as supplied by publisher]

Metabolomics as a complement to phylogenetics for assessing intraspecific boundaries in the desiccation-tolerant medicinal shrub Myrothamnus flabellifolia (Myrothamnaceae).

Mon, 07/01/2019 - 12:28
Metabolomics as a complement to phylogenetics for assessing intraspecific boundaries in the desiccation-tolerant medicinal shrub Myrothamnus flabellifolia (Myrothamnaceae). Phytochemistry. 2019 Jan 03;159:127-136 Authors: Bentley J, Moore JP, Farrant JM Abstract The desiccation-tolerant shrub Myrothamnus flabellifolia has colonised a unique and harsh niche that provides little protection from the elements. It has a wide distribution range in southern Africa, occurring across an environmental gradient that is exceptionally arid in the southwest and highly mesic in the northeast. It is also harvested for use in medicinal preparations, both traditionally and commercially. However, the phytochemical variability of plants from different rainfall regions has not been assessed, nor have the intraspecific relationships been evaluated by means of a rigorously tested phylogeny. The aims of the present study were thus (1) to test a phylogenetic hypothesis for intraspecific relationships in M. flabellifolia; (2) to assess, based on the global metabolomic profiles, whether accessions collected from the three different geographic locations in southern Africa across a rainfall gradient can be differentiated, and if this corroborates the phylogenetic signature; and (3) with the aid of multivariate statistical analysis, identify and evaluate the most significant discriminatory metabolites between the three sampled regions that could act as potential barcodes. The results show that the phylogenetic and metabolomic signatures were congruent, and the metabolomic data were better able to discriminate the different populations collected from the three regions. Several potential barcodes for discriminating the material from the three regions are proposed. Quercetin-rhamnoside and 3-O-methylquercetin, both significant antioxidants, were present at significantly higher quantities in the material from the driest region in the west than from the more mesic regions in the south and east, whereas quercetin-3-O-glucuronide was significantly higher in the latter. A naringenin-like compound or arbutin derivative could discriminate the southern samples from the eastern samples, whereas digalloylglucose differentiated the eastern samples from the southern samples. In summary, the findings of this study imply that the origin of the material should be considered when used in medicinal and cosmetic preparations. PMID: 30611872 [PubMed - as supplied by publisher]

Exploratory metabolomics of nascent metabolic syndrome.

Mon, 07/01/2019 - 12:28
Exploratory metabolomics of nascent metabolic syndrome. J Diabetes Complications. 2018 Dec 10;: Authors: Shim K, Gulhar R, Jialal I Abstract INTRODUCTION: Metabolic syndrome (MetS) is a disorder defined by having three of five features: increased waist circumference (WC), hypertriglyceridemia, decreased high-density lipoprotein-cholesterol, hypertension and an elevated blood glucose (BG). Metabolic Syndrome ( MetS) affects 35% of American adults and significantly increases risk for Atherosclerotic cardiovascular disease (ASCVD) and type-2 diabetes (T2DM). An understanding of the metabolome will help elucidate the pathogenesis of MetS and lead to better management. We hypothesize that the metabolites, gamma-aminobutyric acid (GABA), d-pyroglutamic acid (PGA) and N-acetyl-d-tryptophan (NAT) will be altered in nascent MetS patients without the confounding of ASCVD or T2DM. We also correlated these metabolites with biomarkers of inflammation. PATIENTS AND METHODS: This was an exploratory study of 30 patients with nascent MetS and 20 matched controls undertaken in 2018. Metabolites were evaluated from patient's frozen early morning urine samples and were correlated with biomarkers of inflammation and adipokines. They were assayed by the NIH Western Metabolomics Center using liquid chromatography/mass spectrometry and standardized to urinary creatinine. All patients had normal hepatic and renal function. RESULTS: GABA and PGA levels were significantly increased in MetS patients compared to controls: 2.8-fold and 2.9-fold median increases respectively with p < 0.0001 and p = 0.004, possibly deriving from glutamate. NAT was significantly decreased by 90% in MetS patients compared to controls, p < 0.001. GABA correlates significantly with cardio-metabolic (CM) features including WC, blood pressure systolic (BP-S) while NAT correlated inversely with WC, BP-S, blood glucose (BG) and triglycerides (TG). GABA correlated positively with chemerin, leptin, Fetuin A and endotoxin. NAT correlated inversely with WC, BP-S, BG, TG, high sensitivity C - reactive protein (hsCRP), toll-like receptor-4 (TLR-4), lipopolysaccharide binding protein (LBP), chemerin and retinol binding protein-4 (RBP-4). CONCLUSIONS: We make the novel observation of increased GABA and PGA with decreased NAT in patients with MetS. While GABA and PGA correlates positively with CM features and biomediators of inflammation, the metabolite NAT correlated inversely. Thus, GABA and PGA could contribute to the pro-inflammatory state of MetS while NAT could mitigate this pro-inflammatory response. PMID: 30611573 [PubMed - as supplied by publisher]

Variation patterns in the content of glycosides during green tea manufacturing by a modification-specific metabolomics approach: Enzymatic reaction promoting an increase in the glycosidically bound volatiles at the pan firing stage.

Mon, 07/01/2019 - 12:28
Variation patterns in the content of glycosides during green tea manufacturing by a modification-specific metabolomics approach: Enzymatic reaction promoting an increase in the glycosidically bound volatiles at the pan firing stage. Food Chem. 2019 May 01;279:80-87 Authors: Li P, Zhu Y, Lu M, Yang C, Xie D, Tan J, Peng Q, Zhang Y, Ni D, Dai W, Lin Z Abstract The glycosides are presumed to influence the quality of green tea but the molecular mechanism behind remains unclear. To elucidate the contribution of glycosides to the flavor formation of green tea, changes of both glycosidically bound non-volatiles (GBNVs) and glycosidically bound volatiles (GBVs) during the manufacturing of green tea were investigated using a modification-specific metabolomics method. A total of 64 glycosides (47 GBNVs and 17 GBVs) were identified and their contents mainly changed during the pan firing and drying stages of green tea manufacturing. Notably, the contents of GBVs significantly increased by 1.12-4.46-fold during pan firing. Correlation analysis showed that the GBVs contents were negatively related to the contents of volatiles and glucose. Model experiments revealed that enzymatic synthesis contributed to the increase in the content of GBVs during the pan firing. This comprehensive study on the glycosides changes revealed the molecular bases for GBVs increments during the pan firing. PMID: 30611515 [PubMed - in process]

Untargeted LC-MS based 13C labelling provides a full mass balance of deoxynivalenol and its degradation products formed during baking of crackers, biscuits and bread.

Mon, 07/01/2019 - 12:28
Untargeted LC-MS based 13C labelling provides a full mass balance of deoxynivalenol and its degradation products formed during baking of crackers, biscuits and bread. Food Chem. 2019 May 01;279:303-311 Authors: Stadler D, Lambertini F, Bueschl C, Wiesenberger G, Hametner C, Schwartz-Zimmermann H, Hellinger R, Sulyok M, Lemmens M, Schuhmacher R, Suman M, Berthiller F, Krska R Abstract Deoxynivalenol (DON) is considered to be one of the most important contaminants in cereals and food commodities produced thereof. So far it is not clear i) to which extent DON is degraded during baking and ii) if a degradation results in reduced toxicity. We have elucidated the fate of DON during baking of crackers, biscuits and bread, which were produced from fortified dough and processed under pilot plant conditions. Untargeted stable isotope assisted liquid chromatography (LC) high resolution mass spectrometry was used to determine all extractable degradation products. Targeted LC - tandem mass spectrometry based quantification revealed that DON was partially degraded to isoDON (1.3-3.9%), norDON B (0.2-0.9%) and norDON C (0.3-1.2%). A DON degradation of 6% (crackers), 5% (biscuits) and 2% (bread), respectively, was observed. In vitro translation experiments indicate that isoDON is less toxic than DON. PMID: 30611495 [PubMed - in process]

Comparison of phenolic compounds profile and antioxidant properties of different sweet cherry (Prunus avium L.) varieties.

Mon, 07/01/2019 - 12:28
Comparison of phenolic compounds profile and antioxidant properties of different sweet cherry (Prunus avium L.) varieties. Food Chem. 2019 May 01;279:260-271 Authors: Acero N, Gradillas A, Beltran M, García A, Muñoz Mingarro D Abstract In the present work, three Spanish local varieties of Prunus avium (L.), as well as two foreign varieties were studied. The content of total phenols, flavonoids, anthocyanins, glucose and fructose of methanolic extracts from ripe fruits of each variety were analysed. A phytochemical profile of these cultivars was performed by UHPLC-qTOF-MS. The employed chromatographic method allowed a clear and rapid separation of the three main phenolic compound groups present in the extracts: hydroxycinnamic acids, anthocyanins and flavonoids. In addition, the extracts DPPH radical scavenging ability, as well as their capacity to affect xanthine/xanthine oxidase system, were determined. Finally, variations in ROS intracellular concentrations in HepG2 cell line cultures treated with cherry extracts were measured through DCFH-DA assay. All extracts showed a significant inhibitory effect on the xanthine/xanthine oxidase system. Differences between in vitro and in cell culture results evidence the interaction among the phenolic compounds of the extract. PMID: 30611489 [PubMed - in process]

Untargeted Metabolomics Reveal Defensome-Related Metabolic Reprogramming in Sorghum bicolor against Infection by Burkholderia andropogonis.

Sun, 06/01/2019 - 12:11
Related Articles Untargeted Metabolomics Reveal Defensome-Related Metabolic Reprogramming in Sorghum bicolor against Infection by Burkholderia andropogonis. Metabolites. 2019 Jan 02;9(1): Authors: Mareya CR, Tugizimana F, Piater LA, Madala NE, Steenkamp PA, Dubery IA Abstract Burkholderia andropogonis is the causal agent of bacterial leaf stripe, one of the three major bacterial diseases affecting Sorghum bicolor. However, the biochemical aspects of the pathophysiological host responses are not well understood. An untargeted metabolomics approach was designed to understand molecular mechanisms underlying S. bicolor⁻B. andropogonis interactions. At the 4-leaf stage, two sorghum cultivars (NS 5511 and NS 5655) differing in disease tolerance, were infected with B. andropogonis and the metabolic changes monitored over time. The NS 5511 cultivar displayed delayed signs of wilting and lesion progression compared to the NS 5655 cultivar, indicative of enhanced resistance. The metabolomics results identified statistically significant metabolites as biomarkers associated with the sorghum defence. These include the phytohormones salicylic acid, jasmonic acid, and zeatin. Moreover, metabolic reprogramming in an array of chemically diverse metabolites that span a wide range of metabolic pathways was associated with the defence response. Signatory biomarkers included aromatic amino acids, shikimic acid, metabolites from the phenylpropanoid and flavonoid pathways, as well as fatty acids. Enhanced synthesis and accumulation of apigenin and derivatives thereof was a prominent feature of the altered metabolomes. The analyses revealed an intricate and dynamic network of the sorghum defence arsenal towards B. andropogonis in establishing an enhanced defensive capacity in support of resistance and disease suppression. The results pave the way for future analysis of the biosynthesis of signatory biomarkers and regulation of relevant metabolic pathways in sorghum. PMID: 30609758 [PubMed]

Rac-Mediated Macropinocytosis of Extracellular Protein Promotes Glucose Independence in Non-Small Cell Lung Cancer.

Sun, 06/01/2019 - 12:11
Related Articles Rac-Mediated Macropinocytosis of Extracellular Protein Promotes Glucose Independence in Non-Small Cell Lung Cancer. Cancers (Basel). 2019 Jan 02;11(1): Authors: Hodakoski C, Hopkins BD, Zhang G, Su T, Cheng Z, Morris R, Rhee KY, Goncalves MD, Cantley LC Abstract Cancer cells can adapt to nutrient poor conditions by rewiring their metabolism and using alternate fuel sources. Identifying these adaptive metabolic pathways may provide novel targets for cancer therapy. Here, we identify a subset of non-small cell lung cancer (NSCLC) cell lines that survive in the absence of glucose by internalizing and metabolizing extracellular protein via macropinocytosis. Macropinocytosis is increased in these glucose independent cells, and is regulated by phosphoinositide 3-kinase (PI3K) activation of Rac-Pak signaling. Furthermore, inhibition of Rac-dependent macropinocytosis blocks glucose-independent proliferation. We find that degradation of internalized protein produces amino acids, including alanine, which generates TCA cycle and glycolytic intermediates in the absence of glucose. In this process, the conversion of alanine to pyruvate by alanine transaminase 2 (ALT2) is critical for survival during glucose starvation. Collectively, Rac driven macropinocytosis of extracellular protein is an adaptive metabolic pathway used by a subset of lung cancers to survive states of glucose deprivation, and may serve as a potential drug target for cancer therapy. PMID: 30609754 [PubMed]

Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells.

Sun, 06/01/2019 - 12:11
Related Articles Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells. Metabolites. 2019 Jan 02;9(1): Authors: Warth B, Palermo A, Rattray NJW, Lee NV, Zhu Z, Hoang LT, Cai Y, Mazurek A, Dann S, VanArsdale T, Fantin VR, Shields D, Siuzdak G, Johnson CH Abstract The aims of this study were to determine whether combination chemotherapeutics exhibit a synergistic effect on breast cancer cell metabolism. Palbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6, and when patients are treated in combination with fulvestrant, an estrogen receptor antagonist, they have improved progression-free survival. The mechanisms for this survival advantage are not known. Therefore, we analyzed metabolic and transcriptomic changes in MCF-7 cells following single and combination chemotherapy to determine whether selective metabolic pathways are targeted during these different modes of treatment. Individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy's synergism in the cell model. This study also highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy. PMID: 30609717 [PubMed]

Elemental Metabolomics and Pregnancy Outcomes.

Sun, 06/01/2019 - 12:11
Related Articles Elemental Metabolomics and Pregnancy Outcomes. Nutrients. 2019 Jan 02;11(1): Authors: McKeating DR, Fisher JJ, Perkins AV Abstract Trace elements are important for human health and development. The body requires specific micronutrients to function, with aberrant changes associated with a variety of negative health outcomes. Despite this evidence, the status and function of micronutrients during pregnancy are relatively unknown and more information is required to ensure that women receive optimal intakes for foetal development. Changes in trace element status have been associated with pregnancy complications such as gestational diabetes mellitus (GDM), pre-eclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth. Measuring micronutrients with methodologies such as elemental metabolomics, which involves the simultaneous quantification and characterisation of multiple elements, could provide insight into gestational disorders. Identifying unique and subtle micronutrient changes may highlight associated proteins that are affected underpinning the pathophysiology of these complications, leading to new means of disease diagnosis. This review will provide a comprehensive summary of micronutrient status during pregnancy, and their associations with gestational disorders. Furthermore, it will also comment on the potential use of elemental metabolomics as a technique for disease characterisation and prediction. PMID: 30609706 [PubMed - in process]

Brain Metabolomics Reveal the Antipyretic Effects of Jinxin Oral Liquid in Young Rats by Using Gas Chromatography⁻Mass Spectrometry.

Sun, 06/01/2019 - 12:11
Related Articles Brain Metabolomics Reveal the Antipyretic Effects of Jinxin Oral Liquid in Young Rats by Using Gas Chromatography⁻Mass Spectrometry. Metabolites. 2019 Jan 01;9(1): Authors: Qian W, Shan J, Shen C, Yang R, Xie T, Di L Abstract Pyrexia is considered as a part of host's defense response to the invasion of microorganisms or inanimate matter recognized as pathogenic or alien, which frequently occurs in children. Jinxin oral liquid (JXOL) is a traditional Chinese medicine formula that has been widely used to treat febrile children in China. Experimental fever was induced by injecting yeast into young male Sprague-Dawley rats (80 ± 20 g) and the rectal temperature subsequently changed. Four hours later, the excessive production of interleukin (IL)-1β and prostaglandin (PG) E2 induced by yeast was regulated to normal by JXOL administration. A rat brain metabolomics investigation of pyrexia of yeast and antipyretic effect of JXOL was performed using gas chromatography-mass spectrometry (GC-MS). Clear separation was achieved between the model and normal group. Twenty-two significantly altered metabolites were found in pyretic rats as potential biomarkers of fever. Twelve metabolites, significantly adjusted by JXOL to help relieve pyrexia, were selected out as biomarkers of antipyretic mechanism of JXOL, which were involved in glycolysis, purine metabolism, tryptophan mechanism, etc. In conclusion, the brain metabolomics revealed potential biomarkers in the JXOL antipyretic process and the associated pathways, which may aid in advanced understanding of fever and therapeutic mechanism of JXOL. PMID: 30609645 [PubMed]

A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry.

Sun, 06/01/2019 - 12:11
Related Articles A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry. Talanta. 2019 Mar 01;194:63-72 Authors: Qin Q, Wang B, Wang J, Chang M, Xia T, Shi X, Xu G Abstract Protein-metabolite interactions play important roles in many cellular and physiological processes in biological systems. However, the lack of effective research approaches impedes the understanding of the protein-metabolite interactions. In this study, a novel comprehensive strategy by combining metabolomics platform with native mass spectrometry was developed for investigating the protein-metabolite interactions. Peroxisome proliferator-activated receptors gamma (PPARγ) is a lipid-binding nuclear receptors that plays a key role in regulating fatty-acid oxidation and lipid metabolism, which was selected as the model protein. Seven metabolites including lyso-phosphatidylcholine (LPC) 16:0, LPC18:0, LPC18:1, arachidonic acid, oleic acid, linoleic acid and palmitoleic acid (p < 0.05) were found to have the possible interactions with the PPARγ, these LPCs were discovered as candidate ligands for the first time by using untargeted metabolomics method. Native mass spectrometry based on 15 T Fourier transform ion cyclotron resonance mass spectrometer was employed to directly detect the PPARγ-LPCs complexes to obtain their stoichiometry and kinetic constants. Isothermal titration calorimetry, circular dichroism spectrum and molecular modeling were further utilized to investigate the thermodynamics, conformation and binding mechanism of the interaction between PPARγ and LPCs. It was found that the PPARγ-LPC interaction was an endothermic process, and these LPCs have similar binding constants with stoichiometric number of 1:1. The novel strategy can provide a very useful approach for mapping and identifying unknown protein-metabolite interactions in biological systems. PMID: 30609583 [PubMed - in process]

Metabolomic prostate cancer fields in HRMAS MRS-profiled histologically benign tissue vary with cancer status and distance from cancer.

Sat, 05/01/2019 - 14:54
Related Articles Metabolomic prostate cancer fields in HRMAS MRS-profiled histologically benign tissue vary with cancer status and distance from cancer. NMR Biomed. 2019 Jan 04;:e4038 Authors: Dinges SS, Vandergrift LA, Wu S, Berker Y, Habbel P, Taupitz M, Wu CL, Cheng LL Abstract In this article, we review the state of the field of high resolution magic angle spinning MRS (HRMAS MRS)-based cancer metabolomics since its beginning in 2004; discuss the concept of cancer metabolomic fields, where metabolomic profiles measured from histologically benign tissues reflect patient cancer status; and report our HRMAS MRS metabolomic results, which characterize metabolomic fields in prostatectomy-removed cancerous prostates. Three-dimensional mapping of cancer lesions throughout each prostate enabled multiple benign tissue samples per organ to be classified based on distance from and extent of the closest cancer lesion as well as the Gleason score (GS) of the entire prostate. Cross-validated partial least squares-discriminant analysis separations were achieved between cancer and benign tissue, and between cancer tissue from prostates with high (≥4 + 3) and low (≤3 + 4) GS. Metabolomic field effects enabled histologically benign tissue adjacent to cancer to distinguish the GS and extent of the cancer lesion itself. Benign samples close to either low GS cancer or extensive cancer lesions could be distinguished from those far from cancer. Furthermore, a successfully cross-validated multivariate model for three benign tissue groups with varying distances from cancer lesions within one prostate indicates the scale of prostate cancer metabolomic fields. While these findings could, at present, be potentially useful in the prostate cancer clinic for analysis of biopsy or surgical specimens to complement current diagnostics, the confirmation of metabolomic fields should encourage further examination of cancer fields and can also enhance understanding of the metabolomic characteristics of cancer in myriad organ systems. Our results together with the success of HRMAS MRS-based cancer metabolomics presented in our literature review demonstrate the potential of cancer metabolomics to provide supplementary information for cancer diagnosis, staging, and patient prognostication. PMID: 30609175 [PubMed - as supplied by publisher]

TLC-bioautography identification and GC-MS analysis of antimicrobial and antioxidant active compounds in Musa × paradisiaca L. fruit pulp essential oil.

Sat, 05/01/2019 - 14:54
Related Articles TLC-bioautography identification and GC-MS analysis of antimicrobial and antioxidant active compounds in Musa × paradisiaca L. fruit pulp essential oil. Phytochem Anal. 2019 Jan 04;: Authors: Fahim M, Ibrahim M, Zahiruddin S, Parveen R, Khan W, Ahmad S, Shrivastava B, Shrivastava AK Abstract INTRODUCTION: The absence of microbial growth and resistance to oxidative deterioration in fruits of Musa × paradisiaca L. (bananas) is an indication of the presence of antimicrobial and antioxidant metabolites. OBJECTIVE: In order to investigate the secondary metabolomic spectrum as well as the active antimicrobial and antioxidants present in essential oils (EOs) from fruits of different geographical areas of M. × paradisiaca, gas chromatography-mass spectroscopy (GC-MS) principal component data correlation analysis is complemented with antimicrobial assays and phytochemical and bioautographic antioxidant fingerprints with thin layer chromatography (TLC). METHODOLOGY: An EO was obtained by steam distillation and subjected to GC-MS and TLC for metabolomic profiling from fruit pulp. The antimicrobial potential was tested in both Escherichia coli as a gram negative and Bacillus subtilis as a gram positive microbe. Potential antioxidant metabolites were identified through TLC-bioautography and GC-MS analysis of active zones. RESULTS: A maximum of 0.56% v/w EO was isolated from fruit pulps of M. × paradisiaca. Minimum inhibitory concentrations (MICs) against B. subtillis and E. coli were 0.25 and 0.35 μg/mL, respectively. Thus, 56 metabolites were identified through GC-MS. The major abundant antimicrobial metabolites found in EOs are α-thujene, γ-terpinene, α- and β-pinene, sabinene, β-myrcene, limonene, α-capaene, caryophyllene and (Z,E)-α farnesene. Aceteugenol, palmitic acid, stearic acid, palmitin, and stearin were identified as antioxidant metabolites. Principal component analysis of metabolite data reveals correlations and a clear separation based on metabolites obtained from various areas. CONCLUSION: The data generated using metabolic profiling and cluster analysis helped to identify antimicrobial and antioxidant compounds in M. × paradisiaca. PMID: 30609101 [PubMed - as supplied by publisher]

Real-Time Pure Shift HSQC NMR for Untargeted Metabolomics.

Sat, 05/01/2019 - 14:54
Related Articles Real-Time Pure Shift HSQC NMR for Untargeted Metabolomics. Anal Chem. 2019 Jan 04;: Authors: Timari I, Wang C, Hansen AL, Costa Dos Santos G, Yoon SO, Bruschweiler-Li L, Bruschweiler R Abstract Sensitivity and resolution are key considerations for NMR applications in general, and for metabolomics in particular, where complex mixtures containing hundreds of metabolites over a large range of concentrations are commonly encountered. There is a strong demand for advanced methods that can provide maximal information in the shortest possible time frame. Here we present the optimization and application of the recently introduced 2D real-time BIRD 1H-13C HSQC experiment for NMR-based metabolomics at 13C natural abundance of aqueous samples. For mouse urine samples, it is demonstrated how this real-time pure shift sensitivity improved Heteronuclear Single Quantum Correlation (HSQC-SI) method provides broadband homonuclear decoupling along the proton detection dimension and thereby significantly improves spectral resolution in regions that are affected by spectral overlap. Moreover, the collapse of the scalar multiplet structure of cross-peaks leads to a sensitivity gain of about 40% - 50% over a traditional 2D HSQC-SI experiment. The experiment works well over a range of magnetic field strengths and is particularly useful when resonance overlap in crowded regions of the HSQC spectra hampers accurate metabolite identification and quantitation. PMID: 30608652 [PubMed - as supplied by publisher]

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