PubMed

Related Articles Filtering procedures for untargeted LC-MS metabolomics data. BMC Bioinformatics. 2019 Jun 14;20(1):334 Authors: Schiffman C, Petrick L, Perttula K, Yano Y, Carlsson H, Whitehead T, Metayer C, Hayes J, Rappaport S, Dudoit S Abstract BACKGROUND: Untargeted metabolomics datasets contain large proportions of uninformative features that can impede subsequent statistical analysis such as biomarker discovery and metabolic pathway analysis. Thus, there is a need for versatile and data-adaptive methods for filtering data prior to investigating the underlying biological phenomena. Here, we propose a data-adaptive pipeline for filtering metabolomics data that are generated by liquid chromatography-mass spectrometry (LC-MS) platforms. Our data-adaptive pipeline includes novel methods for filtering features based on blank samples, proportions of missing values, and estimated intra-class correlation coefficients. RESULTS: Using metabolomics datasets that were generated in our laboratory from samples of human blood, as well as two public LC-MS datasets, we compared our data-adaptive filtering method with traditional methods that rely on non-method specific thresholds. The data-adaptive approach outperformed traditional approaches in terms of removing noisy features and retaining high quality, biologically informative ones. The R code for running the data-adaptive filtering method is provided at https://github.com/courtneyschiffman/Metabolomics-Filtering . CONCLUSIONS: Our proposed data-adaptive filtering pipeline is intuitive and effectively removes uninformative features from untargeted metabolomics datasets. It is particularly relevant for interrogation of biological phenomena in data derived from complex matrices associated with biospecimens. PMID: 31200644 [PubMed - in process]

Related Articles Metabolomic insights into polyhydroxyalkanoates production by halophilic bacteria with acetic acid as carbon source. Biosci Biotechnol Biochem. 2019 Jun 14;:1-9 Authors: Wang P, Qiu YQ, Chen XT, Liang XF, Ren LH Abstract A metabolomics method was established to analyze changes of intracellular metabolites and study the mechanism for enhancing polyhydroxyalkanoates production by halotolerant bacteria, Bacillus cereus strain HY-3, using acetic acid as carbon source. Maximum poly(3-hydroxybutyrate) (PHB) contents for the medium with 0.5 g/L and 5.0 g/L of acetic acid were 41.0 ± 0.415% and 49.2 ± 1.21%. Principal components analysis revealed clear metabolic differences in different growth stages and different concentrations of carbon source. According to statistical analysis, 3-hydroxybutyrate (3-HB), serine, threonine, malate, and pyruvate were determined as potential biomarkers for PHB production. Moreover, metabolic pathways analysis indicated that high level of 3-HB in death phase was due to the limitation of carbon source. Metabolism of glycine, serine, and threonine was influential pathway for PHB production among amino acid metabolisms. High levels of organic acids from the TCA cycle could stimulate the carbon source flux into PHB biosynthetic pathway. PMID: 31200628 [PubMed - as supplied by publisher]

Related Articles Comparative Metabolomics of Early Development of the Parasitic Plants Phelipanche aegyptiaca and Triphysaria versicolor. Metabolites. 2019 Jun 13;9(6): Authors: Clermont K, Wang Y, Liu S, Yang Z, dePamphilis CW, Yoder JI, Collakova E, Westwood JH Abstract Parasitic weeds of the family Orobanchaceae attach to the roots of host plants via haustoria capable of drawing nutrients from host vascular tissue. The connection of the haustorium to the host marks a shift in parasite metabolism from autotrophy to at least partial heterotrophy, depending on the level of parasite dependence. Species within the family Orobanchaceae span the spectrum of host nutrient dependency, yet the diversity of parasitic plant metabolism remains poorly understood, particularly during the key metabolic shift surrounding haustorial attachment. Comparative profiling of major metabolites in the obligate holoparasite Phelipanche aegyptiaca and the facultative hemiparasite Triphysaria versicolor before and after attachment to the hosts revealed several metabolic shifts implicating remodeling of energy and amino acid metabolism. After attachment, both parasites showed metabolite profiles that were different from their respective hosts. In P. aegyptiaca, prominent changes in metabolite profiles were also associated with transitioning between different tissue types before and after attachment, with aspartate levels increasing significantly after the attachment. Based on the results from 15N labeling experiments, asparagine and/or aspartate-rich proteins were enriched in host-derived nitrogen in T. versicolor. These results point to the importance of aspartate and/or asparagine in the early stages of attachment in these plant parasites and provide a rationale for targeting aspartate-family amino acid biosynthesis for disrupting the growth of parasitic weeds. PMID: 31200467 [PubMed]

Related Articles Comparison of the Phytochemical Composition of Serenoa repens Extracts by a Multiplexed Metabolomic Approach. Molecules. 2019 Jun 13;24(12): Authors: Marti G, Joulia P, Amiel A, Fabre B, David B, Fabre N, Fiorini-Puybaret C Abstract Phytochemical extracts are highly complex chemical mixtures. In the context of an increasing demand for phytopharmaceuticals, assessment of the phytochemical equivalence of extraction procedures is of utmost importance. Compared to routine analytical methods, comprehensive metabolite profiling has pushed forward the concept of phytochemical equivalence. In this study, an untargeted metabolomic approach was used to cross-compare four marketed extracts from Serenoa repens obtained with three different extraction processes: ethanolic, hexanic and sCO2 (supercritical carbon dioxide). Our approach involved a biphasic extraction of native compounds followed by liquid chromatography coupled to a high-resolution mass spectrometry based metabolomic workflow. Our results showed significant differences in the contents of major and minor compounds according to the extraction solvent used. The analyses showed that ethanolic extracts were supplemented in phosphoglycerides and polyphenols, hexanic extracts had higher amounts of free fatty acids and minor compounds, and sCO2 samples contained more glycerides. The discriminant model in this study could predict the extraction solvent used in commercial samples and highlighted the specific biomarkers of each process. This metabolomic survey allowed the authors to assess the phytochemical content of extracts and finished products of S. repens and unequivocally established that sCO2, hexanic and ethanolic extracts are not chemically equivalent and are therefore unlikely to be pharmacologically equivalent. PMID: 31200456 [PubMed - in process]

16 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 2019/06/15PubMed 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.

44 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 2019/06/14PubMed 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.

16 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 2019/06/13PubMed 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.

16 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 2019/06/13PubMed 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.

Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor α (PPARα). Ecotoxicol Environ Saf. 2019 Jun 08;181:164-171 Authors: Gong Y, Zhang H, Geng N, Ren X, Giesy JP, Luo Y, Xing L, Wu P, Yu Z, Chen J Abstract Short-chain chlorinated paraffins (SCCPs) are frequently detected in environmental matrices and human tissues. It was hypothesized that SCCPs might interact with the peroxisome proliferator-activated receptor α (PPARα). In the present study, an in vitro, dual-luciferase reporter gene assay and in silico molecular docking analysis were employed together to study the interactions between SCCPs congeners and PPARα. Expressions of genes downstream in pathways activated by PPARα in liver of rats exposed to 1, 10, or 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) for 28 days were examined to confirm activation potencies of SCCPs toward PPARα signaling. Effects of exposure to C10-13-CPs (56.5% Cl) on fatty acid metabolism in rat liver were also explored via a pseudo-targeted metabolomics strategy. Our results showed that C10-13-CPs (56.5% Cl) caused a dose-dependent greater expression of luciferase activity of rat PPARα. Molecular docking modeling revealed that SCCPs had a strong capacity to bind with PPARα only through hydrophobic interactions and the binding affinity was dependent on the degree of chlorination in SCCPs congeners. In livers of male rats, exposure to 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) resulted in up-regulated expressions of 11 genes that are downstream in the PPARα-activated pathway and regulate catabolism of fatty acid. Consistently, accelerated fatty acid oxidation was observed mainly characterized by lesser concentrations of ∑fatty acids in livers of rats. Overall, these results demonstrated, for the first time, that SCCPs could activate rat PPARα signaling and thereby disrupt metabolism of fatty acid in livers of male rats. PMID: 31185430 [PubMed - as supplied by publisher]

Metabolomic profiling of CHO fed-batch growth phases at 10, 100 and 1000 L. Biotechnol Bioeng. 2019 Jun 11;: Authors: Vodopivec M, Lah L, Narat M, Curk T Abstract Established bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement and the measurement of physicochemical qualities of the cultivation medium. These methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. However, understanding of the latter is essential for optimization of bioprocess development. Our study employed LC-MS metabolomics as a tool for additional resolution of bioprocess monitoring and was designed at three bioreactors scales (10 L, 100 L, 1000 L) to gain insight into the basal metabolic states of the Chinese hamster ovary (CHO) cell culture during fed-batch. Metabolites characteristic of the four growth stages (early and late exponential phase, stationary phase, and the phase of decline) were identified by multivariate analysis. Enriched metabolic pathways were then established for each growth phase using the CHO metabolic network model. Biomass generation and nucleotide synthesis were enriched in early exponential phase, followed by increased protein production and imbalanced glutathione metabolism in late exponential phase. Glycolysis became downregulated in stationary phase and amino-acid metabolism increased. Phase of culture decline resulted in rise of oxidized glutathione and fatty acid concentrations. Intracellular metabolic profiles of the CHO fed-batch culture were also shown to be consistent with scale and thus demonstrate metabolomic profiling as an informative method to gain physiological insight into the cell culture states during bioprocess regardless of scale. This article is protected by copyright. All rights reserved. PMID: 31184374 [PubMed - as supplied by publisher]

A low ω-6/ω-3 ratio high-fat diet improves rat metabolism via purine and tryptophan metabolism in intestine tract while reversed by inulin. J Agric Food Chem. 2019 Jun 11;: Authors: Xiao Y, Li X, Zeng X, Wang H, Mai Q, Cheng Y, Li J, Tang L, Ding H Abstract BACKGROUND: High-fat diet (HFD) is the main cause of metabolic diseases. However, HFD in previous studies consists of much lard, which contains a large amount of omega-6 (ω-6) polyunsaturated fatty acid (PUFA) and low omega-3 (ω-3) PUFA. The role of ω-6/ω-3 ratio of HFD in the development of metabolic diseases remains incompletely discussed. METHODS: Rats were fed with either a low or a high ω-6/ω-3 ratio HFD singly or combined with inulin. Metabolism state was valued and metabolomics of cecal content were detected. RESULTS: HFD with low ω-6/ω-3 ratio promotes the glucose utilization in rats. However, inulin had different effects on metabolism with different diet. Xanthosine and kynurenic acid in cecum were positively related to epididymal white adipose tissues (eWAT) mass. CONCLUSIONS: The present study indicated the beneficial effects of LRD on rat metabolic state. Moreover, xanthosine and kynurenic acid were closely related to the development of metabolic diseases. PMID: 31184122 [PubMed - as supplied by publisher]

Related Articles A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study. Metabolomics. 2019 Jun 10;15(6):90 Authors: Troisi J, Landolfi A, Vitale C, Longo K, Cozzolino A, Squillante M, Savanelli MC, Barone P, Amboni M Abstract INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment. OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment. METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression. RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment. CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions. PMID: 31183578 [PubMed - in process]

Related Articles A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults. J Immunol Res. 2019;2019:6105059 Authors: Gómez-Arauz AY, Bueno-Hernández N, Palomera LF, Alcántara-Suárez R, De León KL, Méndez-García LA, Carrero-Aguirre M, Manjarrez-Reyna AN, Martínez-Reyes CP, Esquivel-Velázquez M, Ruiz-Barranco A, Baltazar-López N, Islas-Andrade S, Escobedo G, Meléndez G Abstract Sucralose is a noncaloric artificial sweetener that is widely consumed worldwide and has been associated with alteration in glucose and insulin homeostasis. Unbalance in monocyte subpopulations expressing CD11c and CD206 hallmarks metabolic dysfunction but has not yet been studied in response to sucralose. Our goal was to examine the effect of a single sucralose sip on serum insulin and blood glucose and the percentages of classical, intermediate, and nonclassical monocytes in healthy young adults subjected to an oral glucose tolerance test (OGTT). This study was a randomized, placebo-controlled clinical trial. Volunteers randomly received 60 mL water as placebo (n = 20) or 48 mg sucralose dissolved in 60 mL water (n = 25), fifteen minutes prior to an OGTT. Blood samples were individually drawn every 15 minutes for 180 minutes for quantifying glucose and insulin concentrations. Monocyte subsets expressing CD11c and CD206 were measured at -15 and 180 minutes by flow cytometry. As compared to controls, volunteers receiving sucralose exhibited significant increases in serum insulin at 30, 45, and 180 minutes, whereas blood glucose values showed no significant differences. Sucralose consumption caused a significant 7% increase in classical monocytes and 63% decrease in nonclassical monocytes with respect to placebo controls. Pearson's correlation models revealed a strong association of insulin with sucralose-induced monocyte subpopulation unbalance whereas glucose values did not show significant correlations. Sucralose ingestion decreased CD11c expression in all monocyte subsets and reduced CD206 expression in nonclassical monocytes suggesting that sucralose does not only unbalance monocyte subpopulations but also alter their expression pattern of cell surface molecules. This work demonstrates for the first time that a 48 mg sucralose sip increases serum insulin and unbalances monocyte subpopulations expressing CD11c and CD206 in noninsulin-resistant healthy young adults subjected to an OGTT. The apparently innocuous consumption of sucralose should be reexamined in light of these results. PMID: 31183389 [PubMed - in process]

Related Articles Metabolomic Characterization of Human Model of Liver Rejection Identifies Aberrancies Linked to Cyclooxygenase (COX) and Nitric Oxide Synthase (NOS). Ann Transplant. 2019 Jun 11;24:341-349 Authors: Skill NJ, Elliott CM, Ceballos B, Saxena R, Pepin R, Bettcher L, Ellensberg M, Raftery D, Malucio MA, Ekser B, Mangus RS, Kubal CA Abstract BACKGROUND Acute liver rejection (ALR), a significant complication of liver transplantation, burdens patients, healthcare payers, and the healthcare providers due to an increase in morbidity, cost, and resources. Despite clinical resolution, ALR is associated with an increased risk of graft loss. A unique protocol of delayed immunosuppression used in our institute provided a model to characterize metabolomic profiles in human ALR. MATERIAL AND METHODS Twenty liver allograft biopsies obtained 48 hours after liver transplantation in the absence of immunosuppression were studied. Hepatic metabolites were quantitated in these biopsies by liquid chromatography and mass spectroscopy (LC/MS). Metabolite profiles were compared among: 1) biopsies with reperfusion injury but no histological evidence of rejection (n=7), 2) biopsies with histological evidence of moderate or severe rejection (n=5), and 3) biopsies with histological evidence of mild rejection (n=8). RESULTS There were 133 metabolites consistently detected by LC/MS and these were prioritized using variable importance to projection (VIP) analysis, comparing moderate or severe rejection vs. no rejection or mild rejection using partial least squares discriminant statistical analysis (PLS-DA). Twenty metabolites were identified as progressively different. Further PLS-DA using these metabolites identified 3 metabolites (linoleic acid, γ-linolenic acid, and citrulline) which are associated with either cyclooxygenase or nitric oxide synthase functionality. CONCLUSIONS Hepatic metabolic aberrancies associated with cyclooxygenase and nitric oxide synthase function occur contemporaneous with ALR. Additional studies are required to better characterize the role of these metabolic pathways to enhance utility of the metabolomics approach in diagnosis and outcomes of ALR. PMID: 31182705 [PubMed - in process]

Related Articles From intracellular bacteria to differentiated bacteroids: transcriptome and metabolome analysis in Aeschynomene nodules using the Bradyrhizobium sp. ORS285 bclA mutant. J Bacteriol. 2019 Jun 10;: Authors: Lamouche F, Chaumeret A, Guefrachi I, Barrière Q, Pierre O, Guérard F, Gilard F, Giraud E, Dessaux Y, Gakière B, Timchenko T, Kereszt A, Mergaert P, Alunni B Abstract Soil bacteria called rhizobia trigger the formation of root nodules on legume plants. The rhizobia infect these symbiotic organs and adopt an intracellular lifestyle within the nodule cells where they differentiate into nitrogen-fixing bacteroids. Several legume lineages enforce their symbionts into an extreme cellular differentiation, comprising cell enlargement and genome endoreduplication. The antimicrobial peptide transporter BclA is a major determinant of this process in Bradyrhizobium sp. ORS285, a symbiont of Aeschynomene spp.. In the absence of BclA, the bacteria proceed until the intracellular infection of nodule cells but they cannot differentiate into enlarged polyploid and functional bacteroids. The bclA nodule bacteria constitute thus an intermediate stage between the free-living soil bacteria and the nitrogen-fixing bacteroids. Metabolomics on whole nodules of Aeschynomene afraspera and Aeschynomene indica infected with the wild type or the bclA mutant revealed 47 metabolites that differentially accumulated concomitantly with bacteroid differentiation. Bacterial transcriptome analysis of these nodules demonstrated that the intracellular settling of the rhizobia in the symbiotic nodule cells is accompanied with a first transcriptome switch involving several hundreds of upregulated and downregulated genes and a second switch accompanying the bacteroid differentiation, involving less genes but ones that are expressed to extremely elevated levels. The transcriptomes further suggested a dynamic role for oxygen and redox regulation of gene expression during nodule formation and a non-symbiotic function of BclA. Together, our data uncover the metabolic and gene expression changes that accompany the transition from intracellular bacteria into differentiated nitrogen-fixing bacteroids.ImportanceThe legume-rhizobium symbiosis is a major ecological process fueling the biogeochemical nitrogen cycle with reduced nitrogen. It represents also a promising strategy to cut down the use of chemical nitrogen fertilizers in agriculture, thereby improving its sustainability. This interaction leads to the intracellular accommodation of rhizobia within plant cells of symbiotic organs where they differentiate into nitrogen-fixing bacteroids. In specific legume clades, this differentiation process requires the bacterial transporter BclA to counteract antimicrobial peptides produced by the host. Transcriptome analysis of Bradyrhizobium wild-type and bclA mutant bacteria in culture and in symbiosis with Aeschynomene host plants dissected the bacterial transcriptional response in distinct phases and highlighted functions of the transporter in the free-living stage of the bacterial life cycle. PMID: 31182497 [PubMed - as supplied by publisher]

Related Articles Associations between usual food intake and fecal sterols and bile acids: results from the KORA FF4 study. Br J Nutr. 2019 Jun 11;:1-26 Authors: Mitry P, Wawro N, Sharma S, Kriebel J, Artati A, Adamski J, Heier M, Meisinger C, Thorand B, Grallert H, Peters A, Linseisen J Abstract Animal sterols, plant sterols and bile acids in stool samples have been suggested as biomarkers of dietary intake. It is still unknown whether they also reflect long-term habitual dietary intake and can be used in aetiological research. In a subgroup of the KORA FF4 study, habitual dietary intake was estimated based on repeated 24HFL and a FFQ. Stool samples were collected according to a SOP and those meeting the quality criteria were extracted and analysed by means of a metabolomics technique. The present study is based on data from 513 men and 495 women with a mean age of 60 and 58 years, respectively, for which fecal animal and plant sterols and bile acids concentrations and dietary intake data were available. In adjusted regression models, the associations between food intake and log-normalised metabolite concentrations were analysed. Bonferroni correction was used to account for multiple testing. In this population-based sample, associations between habitual dietary intake and fecal concentrations of animal sterols were identified, while the impact of usual diet on bile acids was limited. A habitual diet high in 'fruits' and 'nuts and seeds' is associated with lower animal fecal sterols concentrations, whereas a diet high in 'meat and meat products' is positively related to fecal concentrations of animal sterols. A positive association between glycocholate and fruit consumption was found. Further studies are necessary for evaluation of fecal animal sterols as biomarkers of diet. The findings need to be confirmed in other populations with diverse dietary habits. PMID: 31182174 [PubMed - as supplied by publisher]

Related Articles Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells. Cancers (Basel). 2019 Jun 09;11(6): Authors: Melzer C, Rehn V, Yang Y, Bähre H, von der Ohe J, Hass R Abstract MSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-lethal concentrations of taxol for 24 h, exosomes were isolated and applied to different human cancer populations including A549 lung cancer, SK-OV-3 ovarian cancer, and MDA-hyb1 breast cancer cells. While MSC control exosomes revealed little if any growth inhibition on the tumor cells, exposure to taxol-loaded MSC-derived exosomes was associated with 80-90% cytotoxicity. A similar application of taxol-loaded exosomes from HuVEC displayed much fewer effects. Quantification by LC-MS/MS analysis demonstrated a 7.6-fold reduced taxol concentration in MSC exosomes when compared to equivalent cytotoxic in vitro effects achieved with taxol substances, indicating a specific and more efficient tumor-targeting property. Consequently, MSC-derived taxol exosomes were tested in vivo. Highly metastatic MDA-hyb1 breast tumors were induced in NODscid mice, and systemic intravenous application of MSC-derived taxol exosomes revealed a more than 60% reduction of subcutaneous primary tumors. Moreover, the amount of distant organ metastases observed at least in lung, liver, spleen, and kidney was reduced by 50% with MSC taxol exosomes, similar to the effects observed with taxol, although the concentration of taxol in exosomes was about 1000-fold reduced. Together, these findings in different cancer cell populations and in vivo provide promising future perspectives for drug-loaded MSC-derived exosomes in efficiently targeting primary tumors and metastases by reducing side effects. PMID: 31181850 [PubMed]

Related Articles Snail-Overexpression Induces Epithelial-mesenchymal Transition and Metabolic Reprogramming in Human Pancreatic Ductal Adenocarcinoma and Non-tumorigenic Ductal Cells. J Clin Med. 2019 Jun 08;8(6): Authors: Liu M, Hancock SE, Sultani G, Wilkins BP, Ding E, Osborne B, Quek LE, Turner N Abstract The zinc finger transcription factor Snail is a known effector of epithelial-to-mesenchymal transition (EMT), a process that underlies the enhanced invasiveness and chemoresistance of common to cancerous cells. Induction of Snail-driven EMT has also been shown to drive a range of pro-survival metabolic adaptations in different cancers. In the present study, we sought to determine the specific role that Snail has in driving EMT and adaptive metabolic programming in pancreatic ductal adenocarcinoma (PDAC) by overexpressing Snail in a PDAC cell line, Panc1, and in immortalized, non-tumorigenic human pancreatic ductal epithelial (HPDE) cells. Snail overexpression was able to induce EMT in both pancreatic cell lines through suppression of epithelial markers and upregulation of mesenchymal markers alongside changes in cell morphology and enhanced migratory capacity. Snail-overexpressed pancreatic cells additionally displayed increased glucose uptake and lactate production with concomitant reduction in oxidative metabolism measurements. Snail overexpression reduced maximal respiration in both Panc1 and HPDE cells, with further reductions seen in ATP production, spare respiratory capacity and non-mitochondrial respiration in Snail overexpressing Panc1 cells. Accordingly, lower expression of mitochondrial electron transport chain proteins was observed with Snail overexpression, particularly within Panc1 cells. Modelling of 13C metabolite flux within both cell lines revealed decreased carbon flux from glucose in the TCA cycle in snai1-overexpressing Panc1 cells only. This work further highlights the role that Snail plays in EMT and demonstrates its specific effects on metabolic reprogramming of glucose metabolism in PDAC. PMID: 31181802 [PubMed]

Related Articles Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics. Metabolites. 2019 Jun 08;9(6): Authors: Quell JD, Römisch-Margl W, Haid M, Krumsiek J, Skurk T, Halama A, Stephan N, Adamski J, Hauner H, Mook-Kanamori D, Mohney RP, Daniel H, Suhre K, Kastenmüller G Abstract Kit-based assays, such as AbsoluteIDQTM p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally-relevant information on the detailed fatty acid side-chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side-chain resolving LipidyzerTM platform, analyzing 223 samples in parallel to the AbsoluteIDQTM. Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological data sets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data. PMID: 31181753 [PubMed]

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 2019/06/11PubMed 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.