PubMed

Related Articles Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population. Clin Cancer Res. 2017 Mar 15;23(6):1422-1431 Authors: Hart CD, Vignoli A, Tenori L, Uy GL, Van To T, Adebamowo C, Hossain SM, Biganzoli L, Risi E, Love RR, Luchinat C, Di Leo A Abstract Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)-negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial.Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic.Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score.Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422-31. ©2017 AACR. PMID: 28082280 [PubMed - indexed for MEDLINE]

Related Articles Mining Microbial Signals for Enhanced Biodiscovery of Secondary Metabolites. Methods Mol Biol. 2017;1539:287-300 Authors: Reen FJ, Gutiérrez-Barranquero JA, O'Gara F Abstract The advent of metagenomics based biodiscovery has provided researchers with previously unforeseen access to the rich tapestry of natural bioactivity that exists in the biosphere. Unhindered by the "culturable bottleneck" that has severely limited the translation of the genetic potential that undoubtedly exists in nature, metagenomics nonetheless requires ongoing technological developments to maximize its efficacy and applicability to the discovery of new chemical entities.Here we describe methodologies for the detection and isolation of quorum sensing (QS) signal molecules from metagenomics libraries. QS signals have already shown considerable potential for the activation and "awakening" of biosynthetic gene clusters, bridging the existing divide between the natural product repertoire and the natural biosynthetic biodiversity hinted at by nature's blueprint. The QS pipeline from high-throughput robotics to functional screening and hit isolation is detailed, highlighting the multidisciplinary nature of progressive biodiscovery programs. PMID: 27900698 [PubMed - indexed for MEDLINE]

Related Articles Retrospective analysis of pesticide metabolites in urine using liquid chromatography coupled to high-resolution mass spectrometry. Talanta. 2016 Nov 01;160:547-555 Authors: López A, Dualde P, Yusà V, Coscollà C Abstract A comprehensive retrospective analysis of pesticide metabolites in urine was developed, using liquid chromatography coupled to Orbitrap high-resolution mass spectrometry (UHPLC-HRMS) that includes both post-run target (suspect screening) and non-target screening. An accurate-mass database comprising 263 pesticide metabolites was built and used for the post-run screening analysis. For non-target analysis, a "fragmentation-degradation" relationship strategy was selected. The proposed methodology was applied to 49 real urine samples from pregnant women. In the post-target analysis 26 pesticide metabolites were tentatively identified, 8 of which (2-diethylamino-6-methyl-pyrimidinol; 3-ketocarbofuran; 4,6-dimethoxy-2-pyrimidinamine; 4-hydroxy-2-isporopyl-6-methylpyrimidine; diethyl malate; diethyl maleate; N-(2-Ethyl-6-methylphenyl)-2-hydroxyacetamide and propachlor oxanilic acid ) were confirmed using analytical standards. Likewise, one unknown degradation product, methyl-N-phenylcarbamate was elucidated in the non-target screening. Finally, the real urine samples were grouped according to their origin applying a metabolomic approach. PMID: 27591649 [PubMed - indexed for MEDLINE]

31 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 2018/02/08PubMed 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.

31 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 2018/02/08PubMed 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.

21 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 2018/02/07PubMed 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.

21 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 2018/02/07PubMed 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.

20 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 2018/02/06PubMed 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.

20 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 2018/02/06PubMed 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.

Jasmonate-Responsive MYB Factors Spatially Repress Rutin Biosynthesis in Fagopyrum Tataricum. J Exp Bot. 2018 Jan 31;: Authors: Zhang K, Logacheva MD, Meng Y, Hu J, Wan D, Li L, Dagmar J, Wang Z, Georgiev MI, Yu Z, Yang F, Yan M, Zhou M Abstract Jasmonates (JAs) are plant hormones that induce many secondary metabolites accumulation, such as rutin in buckwheat, via regulation of JAs-responsive transcription factors (TFs). Here, we report on the identification of a clade of JAs-responsive subgroup 4 MYB TFs, FtMYB13, FtMYB14, FtMYB15 and FtMYB16, directly repressing rutin biosynthesis in Fagopyrum tataricum. Immunoblot analysis showed that FtMYB13, FtMYB14 and FtMYB15 could be degraded via 26S proteasome in COI1-dependent JA signaling pathway, and this degradation is due to the SID motif in their C-terminus. Yeast two hybrid (Y2H) and Bimolecular Fluorescence Complementation (BiFC) assays revealed that FtMYB13, FtMYB14 and FtMYB15 interact with the importin protein 'Sensitive to ABA and Drought 2' (FtSAD2) in stem and inflorescence. Furthermore, the key repressor of JAs signaling FtJAZ1 specifically interacts with FtMYB13. Point mutation analysis showed that the conserved Asp residue of SID domain contributes to mediate the protein-protein interaction. Protoplasts transient activation assays demonstrated that FtMYB13, FtMYB14 and FtMYB15 directly repress phenylalanine ammonia lyase (FtPAL) gene expression and FtSAD2 and FtJAZ1 significantly promote the repressing activity of FtMYBs. These findings may ultimately be promising for further engineering of plant secondary metabolisms. PMID: 29394372 [PubMed - as supplied by publisher]

Contrasting Metabolic Profiles of Tasty Tomato Fruit of the Andean Varieties in Comparison with Commercial Ones. J Sci Food Agric. 2018 Feb 02;: Authors: D's Angelo M, Zanor MI, Sance M, Cortina PR, Boggio SB, Asprelli P, Carrari F, Santiago AN, Asís R, Peralta IE, Valle EM Abstract BACKGROUND: Fruits of most commercial tomato (Solanum lycopersicum L.) cultivars are deficient in flavour. In contrast, traditional "criollo" tomato varieties are appreciated for fruit of excellent organoleptic quality. Small farmers from Argentine Andean Valleys have maintained their own tomato varieties, which were selected mainly for flavour. This work aims to correlate the chemical composition of the fruit with the sensory attributes of eight heirloom tomato varieties. The long-term goal is to identify potential candidate genes capable of altering chemicals involved in flavour. RESULTS: Sensory analysis and metabolomics of fruit were determined. The data revealed that defined tomato aroma and sourness correlated with citrate, and several volatile organic compounds (VOC), such as α-terpineol, p-menth-1-en-9-al, linalool and 3,6-dimethyl-2,3,3a,4,5,7a-hexahydrobenzofuran (DMHEX), a novel volatile recently identified in tomato. Instead, the sensory attributes sweetness and not acidic taste correlated with characteristic tomato taste, and, besides fructose and glucose, with two VOCs, benzaldehyde, and 2-methyl-2-octen-4-one. CONCLUSIONS: These data provide new evidences of the complex chemical combination that induced the flavour and aroma of the good-tasting "criollo" tomato fruit. That is, the compounds that correlated with defined tomato aroma and acidic taste did not correlate with sweetness, or with characteristic tomato taste. PMID: 29393974 [PubMed - as supplied by publisher]

Comprehensive metabolite profiling in distinct chemotypes of Commiphora wightii. Nat Prod Res. 2018 Feb 02;:1-7 Authors: Bhatia A, Tripathi T, Singh S, Bisht H, Behl HM, Roy R, Sidhu OP Abstract Commiphora wightii (Arn.) Bhandari, known as guggul, produces a medicinally important gum resin which is used extensively by Ayurvedic physicians to treat various ailments. However, most of the studies on C. wightii have been limited to its gum resin. Comprehensive metabolic profiling of leaves, stem and gum resin samples was undertaken to analyse aqueous and non-aqueous metabolites from three distinct chemotypes (NBRI-101, NBRI-102 and NBRI-103) shortlisted from different agro-climatic zones. GC-MS, HPLC and NMR spectroscopy were used for comprehensive metabolomics. Multivariate analysis showed characteristic variation in quinic and citric acids, myo-inositol and glycine (aqueous metabolites) and 2,6-di-tert-butyl-phenol, trans-farnesol and guggulsterones (non-aqueous metabolites) amongst the three chemotypes. Quinic acid, citric acid and myo-ionositol were detected in substantial quantities from leaves and stem samples which provide opportunities for novel nutraceutical and pharmaceutical formulations. Quinic acid, from the leaves, was identified as a marker metabolite for early selection of high guggulsterones-yielding cultivars. PMID: 29393680 [PubMed - as supplied by publisher]

Impact of CHO Metabolism on Cell Growth and Protein Production: An Overview of Toxic and Inhibiting Metabolites and Nutrients. Biotechnol J. 2018 Feb 02;: Authors: Pereira S, Kildegaard HF, Andersen MR Abstract For over three decades, Chinese hamster ovary (CHO) cells have been the chosen expression platform for the production of therapeutic proteins with complex post-translational modifications. However, the metabolism of these cells is far from perfect and optimized, and requires substantial knowhow and process optimization and monitoring to perform efficiently. One of the main reasons for this is the production and accumulation of toxic and growth-inhibiting metabolites during culture. Lactate and ammonium are the most known, but many more have been identified. In this review, we present an overview of metabolites that deplete and accumulate throughout the course of cultivations with toxic and growth inhibitory effects to the cells. We further provide an overview of the CHO metabolism with emphasis to metabolic pathways of amino acids, glutathione (GSH), and related compounds which have growth-inhibiting and/or toxic effect on the cells. Additionally, we survey relevant publications which describe the applications of metabolomics as a powerful tool for revealing which reactions occur in the cell under certain conditions and identify growth-inhibiting and toxic metabolite. We also present a number of resources that describe the cellular mechanisms of CHO and are available on-line. Finally, we discuss the application of this knowledge for bioprocess and medium development and cell line engineering.. PMID: 29393587 [PubMed - as supplied by publisher]

Integration of transcriptomics, proteomics, metabolomics and systems pharmacology data to reveal the therapeutic mechanism underlying Chinese herbal Bufei Yishen formula for the treatment of chronic obstructive pulmonary disease. Mol Med Rep. 2018 Jan 25;: Authors: Zhao P, Li J, Yang L, Li Y, Tian Y, Li S Abstract Bufei Yishen formula (BYF) is a traditional Chinese medicine formula, which has long been used as a therapeutic agent for the treatment of chronic obstructive pulmonary disease (COPD). Systems pharmacology has previously been used to identify the potential targets of BYF, and an experimental study has demonstrated that BYF is able to prevent COPD. In addition, the transcriptomic and metabolomic profiles of lung tissues from rats with COPD and BYF‑treated rats have been characterized. The present study aimed to determine the therapeutic mechanisms underlying the effects of BYF on COPD treatment by integrating transcriptomics, proteomics and metabolomics, together with systems pharmacology datasets. Initially, the proteomic profiles of rats with COPD and BYF‑treated rats were analyzed. Subsequently, pathway and network analyses were conducted to integrate three‑omics data; the results demonstrated that the genes, proteins and metabolites were predominantly associated with oxidoreductase activity, antioxidant activity, focal adhesion and lipid metabolism. Finally, a comprehensive analysis of systems pharmacology, transcriptomic, proteomic and metabolomic datasets was performed, and numerous genes, proteins and metabolites were found to be regulated in BYF‑treated rats; the potential target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhesion. In conclusion, BYF exerted beneficial effects against COPD, potentially by modulating lipid metabolism, the inflammatory response, oxidative stress and cell junction pathways at the system level. PMID: 29393428 [PubMed - as supplied by publisher]

Metabolomics reveals the depletion of intracellular metabolites in HepG2 cells after treatment with gold nanoparticles. Nanotoxicology. 2018 Feb 02;:1-12 Authors: Lindeque JZ, Matthyser A, Mason S, Louw R, Taute CJF Abstract Studies on the safety of gold nanoparticles (GNPs) are plentiful due to their successful application in drug delivery and treatment of diseases in trials. Cytotoxicity caused by GNPs has been studied on the physiological and biochemical level; yet, the effect of GNPs (particularly gold nano-spheres) on the metabolome of living organisms remains understudied. In this investigation, metabolomics was used to comprehensively study the metabolic alterations in HepG2 cells caused by GNPs; and to investigate the role of representative GNP coatings. GNPs were synthesized, coated and characterized before use on HepG2 cell cultures. Cells were treated for 3 h with citrate-, poly-(sodiumsterene sulfunate)-, and poly-vinylpyrrolidone (PVP)-capped GNPs, respectively. The internalization of the different GNPs and their effect on mitochondrial respiration and the metabolome were studied. Results indicated that the PVP-capped GNPs internalized more and also caused a more observable effect on the metabolome. Conversely, it was the citrate- and poly-(sodiumsterene sulfunate) coated particles that influenced ATP production in addition to the metabolomic changes. A holistic depletion of intracellular metabolites was observed regardless of GNP coating, which hints to the binding of certain metabolites to the particles. PMID: 29392969 [PubMed - as supplied by publisher]

One after the other: A novel Bluetongue virus strain related to Toggenburg virus detected in the Piedmont region (North-western Italy), extends the panel of novel atypical BTV strains. Transbound Emerg Dis. 2018 Feb 02;: Authors: Marcacci M, Sant S, Mangone I, Goria M, Dondo A, Zoppi S, van Gennip RGP, Radaelli MC, Cammà C, van Rijn PA, Savini G, Lorusso A Abstract In this rapid communication, a novel atypical bluetongue virus (BTV) strain detected in goats in the Piedmont region (north-western Italy) is described. This strain, BTV-Z ITA2017, is most related in Seg-2/VP-2 (83.8% nt/82.7% aa) to strain TOV of BTV-25. Reactive antisera of goats positive by cELISA for BTV antibodies failed to neutralize a chimeric virus expressing the outermost protein of TOV. Infected animals displayed low levels of RNAemia and absence of clinical signs consistent with bluetongue infection, a scenario described in animals infected with atypical BTV strains. PMID: 29392882 [PubMed - as supplied by publisher]

Metabolomic Analysis of Glioma Cells Using Nanoflow Liquid Chromatography-Tandem Mass Spectrometry. Methods Mol Biol. 2018;1741:125-134 Authors: Deng J, Zhang G, Neubert TA Abstract Mass spectrometry (MS)-based techniques have been finding utility as sensitive, high throughput metabolite analysis tools for complex biological samples. We describe here a nanoflow liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system we developed and applied to metabolic profiling of human cells. Metabolites are extracted from cells using methanol, and filtered through a C18 StageTip to remove large particles. Metabolite samples are separated by HPLC at a flow rate of 400-500 nl/min, then analyzed in both positive and negative ion modes in an LTQ-Orbitrap MS. Metabolite identification and differential analysis are performed using commercial or open source software. Protocols outlined in this chapter describe how nano-LC-MS can be applied to investigate metabolic profiling with limited biomass amount. PMID: 29392696 [PubMed - in process]

Comprehensive Metabolomics Studies of Plant Developmental Senescence. Methods Mol Biol. 2018;1744:339-358 Authors: Watanabe M, Tohge T, Balazadeh S, Erban A, Giavalisco P, Kopka J, Mueller-Roeber B, Fernie AR, Hoefgen R Abstract Leaf senescence is an essential developmental process that involves diverse metabolic changes associated with degradation of macromolecules allowing nutrient recycling and remobilization. In contrast to the significant progress in transcriptomic analysis of leaf senescence, metabolomics analyses have been relatively limited. A broad overview of metabolic changes during leaf senescence including the interactions between various metabolic pathways is required to gain a better understanding of the leaf senescence allowing to link transcriptomics with metabolomics and physiology. In this chapter, we describe how to obtain comprehensive metabolite profiles and how to dissect metabolic shifts during leaf senescence in the model plant Arabidopsis thaliana. Unlike nucleic acid analysis for transcriptomics, a comprehensive metabolite profile can only be achieved by combining a suite of analytic tools. Here, information is provided for measurements of the contents of chlorophyll, soluble proteins, and starch by spectrophotometric methods, ions by ion chromatography, thiols and amino acids by HPLC, primary metabolites by GC/TOF-MS, and secondary metabolites and lipophilic metabolites by LC/ESI-MS. These metabolite profiles provide a rich catalogue of metabolic changes during leaf senescence, which is a helpful database and blueprint to be correlated to future studies such as transcriptome and proteome analyses, forward and reverse genetic studies, or stress-induced senescence studies. PMID: 29392679 [PubMed - in process]

Arbuscular Mycorrhizal Fungi and Plant Chemical Defence: Effects of Colonisation on Aboveground and Belowground Metabolomes. J Chem Ecol. 2018 Feb 02;: Authors: Hill EM, Robinson LA, Abdul-Sada A, Vanbergen AJ, Hodge A, Hartley SE Abstract Arbuscular mycorrhizal fungal (AMF) colonisation of plant roots is one of the most ancient and widespread interactions in ecology, yet the systemic consequences for plant secondary chemistry remain unclear. We performed the first metabolomic investigation into the impact of AMF colonisation by Rhizophagus irregularis on the chemical defences, spanning above- and below-ground tissues, in its host-plant ragwort (Senecio jacobaea). We used a non-targeted metabolomics approach to profile, and where possible identify, compounds induced by AMF colonisation in both roots and shoots. Metabolomics analyses revealed that 33 compounds were significantly increased in the root tissue of AMF colonised plants, including seven blumenols, plant-derived compounds known to be associated with AMF colonisation. One of these was a novel structure conjugated with a malonyl-sugar and uronic acid moiety, hitherto an unreported combination. Such structural modifications of blumenols could be significant for their previously reported functional roles associated with the establishment and maintenance of AM colonisation. Pyrrolizidine alkaloids (PAs), key anti-herbivore defence compounds in ragwort, dominated the metabolomic profiles of root and shoot extracts. Analyses of the metabolomic profiles revealed an increase in four PAs in roots (but not shoots) of AMF colonised plants, with the potential to protect colonised plants from below-ground organisms. PMID: 29392532 [PubMed - as supplied by publisher]

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism. Metabolomics. 2017;13(11):127 Authors: Sattler K, Behnes M, Barth C, Wenke A, Sartorius B, El-Battrawy I, Mashayekhi K, Kuschyk J, Hoffmann U, Papavasiliu T, Fastner C, Baumann S, Lang S, Zhou X, Yücel G, Borggrefe M, Akin I Abstract Background: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet. Objectives: We aimed to study the effects of interventional LAAC on systemic metabolism. Methods: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1). Results: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta -0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01). Conclusions: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future. PMID: 29391863 [PubMed]