PubMed

Related Articles Metabolomic profiling and anti-infective potential of Zinnia elegans and Gazania rigens (Family Asteraceae). Nat Prod Res. 2018 Dec 22;:1-4 Authors: Gomaa AA, Samy MN, Abdelmohsen UR, Krischke M, Mueller MJ, Wanas AS, Desoukey SY, Kamel MS Abstract The present study evaluates the chemical composition of Zinnia elegans and Gazania rigens based on their metabolomic profiles using liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS), alongside with the anti-infective activities of their ethanol extracts, as well as, different fractions. A significant difference was observed between the LC-MS profiles of the two plants such as, coumarins, sesquiterpene lactones and phenylethanoids which were characteristic for Z. elegans, while amides and phenolic acid derivatives were characteristic for G. rigens. These results highlight the chemical potential of Z. elegans and G. rigens. Furthermore, the ethyl acetate fraction of Z. elegans showed a significant antimalarial activity with IC50 values of 21.03 and 13.72 µg/mL against Plasmodium falciparum D6 and P. falciparum W2, respectively. PMID: 30580583 [PubMed - as supplied by publisher]

Related Articles Development of A Correlative Strategy to Discover Colorectal Tumor Tissue Derived Metabolite Biomarkers in Plasma Using Untargeted Metabolomics. Anal Chem. 2018 Dec 23;: Authors: Wang Z, Cui B, Zhang F, Yang Y, Shen X, Li Z, Zhao W, Zhang Y, Deng K, Rong Z, Yang K, Yu X, Li K, Han P, Zhu ZJ Abstract The metabolic profiling of biofluids using untargeted metabolomics provides a promising choice to discover metabolite biomarkers for clinical cancer diagnosis. However, metabolite biomarkers discovered in biofluids may not necessarily reflect the pathological status of tumor tissue, which makes these biomarkers difficult to reproduce. In this study, we developed a new analysis strategy by integrating the univariate and multivariate correlation analysis approach to discover tumor tissue derived (TTD) metabolites in plasma samples. Specifically, untargeted metabolomics was first used to profile a set of paired tissue and plasma samples from 34 colorectal cancer (CRC) patients. Then, univariate correlation analysis was used to select correlative metabolite pairs between tissue and plasma, and a random forest regression model was utilized to define 243 TTD metabolites in plasma samples. The TTD metabolites in CRC plasma were demonstrated to accurately reflect the pathological status of tumor tissue, and have great potentials for metabolite biomarker discovery. Accordingly, we conducted a clinical study using a set of 146 plasma samples from CRC patients and gender-matched polyp controls to discover metabolite biomarkers from TTD metabolites. As a result, eight metabolites were selected as potential biomarkers for CRC diagnosis with high sensitivity and specificity. For CRC patients after surgery, the survival risk score defined by metabolite biomarkers also performed well in predicting overall survival time (p = 0.022) and progression free survival time (p = 0.002). In conclusion, we developed a new analysis strategy which effectively discovers tumor tissue related metabolite biomarkers in plasma for cancer diagnosis and prognosis. PMID: 30580524 [PubMed - as supplied by publisher]

Related Articles Incompatibility assessment of Genkwa Flos and Glycyrrhizae Radix et Rhizoma with biochemical, histopathological and metabonomic approach. J Ethnopharmacol. 2019 Jan 30;229:222-232 Authors: Chen YY, Tang YP, Shang EX, Zhu ZH, Tao WW, Yu JG, Feng LM, Yang J, Wang J, Su SL, Zhou H, Duan JA Abstract ETHNOPHARMACOLOGICAL RELEVANCE: As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence. AIMS OF STUDY: In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach. MATERIALS AND METHODS: Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis. RESULTS: Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism. CONCLUSION: The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats. PMID: 30339979 [PubMed - indexed for MEDLINE]

Related Articles Transcriptomics and metabonomics of the anti-aging properties of total flavones of Epimedium in relation to lipid metabolism. J Ethnopharmacol. 2019 Jan 30;229:73-80 Authors: Wu B, Xiao X, Li S, Zuo G Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Total flavones of Epimedium (TFE) is the main active ingredient in Herba Epimedii, which is a well-known Chinese herbal medicine that is widely used to treat certain age-related diseases in oriental countries. AIM OF THE STUDY: The aim of this work was to investigate the anti-aging properties of TFE related to lipid metabolism. MATERIALS AND METHODS: Both transcriptomics and metabonomics were applied in this work to investigate the anti-aging properties of TFE. Microarray and LC-MS analysis were conducted on liver samples of three groups of rats, including young (4 months), old (24 months), and old rats administrated TFE. RESULTS: Transcriptomics analysis highlighted 287 transcripts related to the anti-aging effect of TFE, in which the expression ratio of 18 genes regulating lipid metabolism, including HMGCS1 and NR1H3, returned to normal levels after TFE treatment. In addition, 24 aging-related metabolites were discovered in a metabonomics study, and 15 of these were structurally identified, including palmitic amide, linoleamide, and oleamide. Bioinformatics and integral data analysis on the results of the transcriptomics and metabonomics suggest the involvement of 12 key metabolic pathways, half of which are highly related to lipid metabolism. CONCLUSIONS: This study demonstrates that the role played by TFE in the lipid metabolism of aging rats is multifaceted and multi-layered. PMID: 30278205 [PubMed - indexed for MEDLINE]

Related Articles A novel 3D breast-cancer-on-chip platform for therapeutic evaluation of drug delivery systems. Anal Chim Acta. 2018 Dec 07;1036:97-106 Authors: Chen Y, Gao D, Wang Y, Lin S, Jiang Y Abstract The ability to rapidly screen drugs and drug delivery systems with a more accurate tumor model to better predict their in vivo performance is of great importance in drug development, because there have been some limitations in currently used tumor models. To address this problem, we developed an in vitro breast tumor model on a chip, composed of a microvessel wall, the extracellular matrix (ECM) and uniformly sized multicellular tumor spheroids (MCTS), for the evaluation of nanoparticle-based drug delivery systems. A carbon dots (CDs)-based drug delivery system was synthesized as a model to evaluate the real-time monitoring ability of the system transport through the endothelium and the penetrability into MCTS with a high spatio-temporal resolution on the established platform. Moreover, a modified 96-well plate was used to hold the microfluidic devices for in situ cytotoxicity assays of the MCTS by a microplate reader. Our findings revealed that the synthesized drug delivery system could be transported across an endothelial monolayer within 3 h and was nontoxic to the cells throughout the experiment. In addition, we demonstrated the capabilities of this model by assessing the delivery and efficacy of the drug delivery system in BT549 and T47D spheroids, two cell lines representative of triple negative breast cancer (TNBC) and non-TNBC, respectively. This microfluidic platform enables evaluation of dynamic transport behavior and in situ cytotoxicity evaluation in one system. The established platform provides a more accurate and low-cost in vitro model for rapid drug screening in pre-clinical studies. PMID: 30253842 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic changes induced by nicotine in adult zebrafish skeletal muscle. Ecotoxicol Environ Saf. 2018 Nov 30;164:388-397 Authors: Gómez-Canela C, Prats E, Lacorte S, Raldúa D, Piña B, Tauler R Abstract Acute exposure to nicotinic agonists induces myotoxicity in zebrafish embryos. The main goal of this work was to evaluate the potential myotoxicity of nicotine acetylcholine receptor agonists on adult zebrafish muscle tissue by using nicotine as a model compound. Liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) datasets were processed with different chemometric tools based on the selection of Regions of Interest (ROI) and Multivariate Curve-Resolution (ROI-MCR procedure) Alternating Least Squares (ALS) for the analysis of different exposure experiments. Analysis of Variance Simultaneous Component Analysis (ASCA) of changes on metabolite peak profile areas showed significant nicotine concentration and exposure time-dependent changes, clearly differentiating between exposed and non-exposed samples and between short (2 h) and long exposure times (6 h or 24 h). Most of the changes observed in the concentrations of different metabolites are probably secondary to the observed hyperlocomotion, as they have been also observed in humans after strenuous muscular exercise. The absence of myotoxicity might be related with the reduced calcium permeability of adult muscle-type nicotinic acetylcholine receptors (nAChRs). PMID: 30142605 [PubMed - indexed for MEDLINE]

28 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 2018/12/24PubMed 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.

Related Articles GC/MS-based metabolomics analysis reveals active fatty acids biosynthesis in the Filippi's gland of the silkworm, Bombyx mori, during silk spinning. Insect Biochem Mol Biol. 2018 Dec 18;: Authors: Wang X, Li Y, Liu Q, Tan X, Xie X, Xia Q, Zhao P Abstract The Filippi's gland, also called the Lyonet's gland, is in truth a pair of tiny glands that are unique to lepidopteran insects. Although the ultrastructure of the Filippi's gland has been well-understood, the specific biological function of this gland in silk spinning is still unclear. Previous studies proposed a hypothesis that this gland might synthesize and secrete some substances into the anterior silk gland (ASG) to help silk spinning. In order to identify these metabolites, a GC/MS-based metabolomics technique was introduced. A total of 59 metabolites, including fatty acids, amino acids, and sugars, were identified in glands from silkworm larvae in the feeding and silk spinning stages. Abundance and pathway analyses revealed that these metabolites had different abundances during gland development and silk spinning, which may facilitate the transport of small molecules and ions. The most interesting result is that the Filippi's gland has a very active fatty acid biosynthesis process during spinning, suggesting that it may synthesize lipids or waxes and secrete them into the ASG to promote silk spinning. This data provides instructive insight into the biological functions of Filippi's gland from both silkworms and other lepidoptera. PMID: 30576753 [PubMed - as supplied by publisher]

Related Articles Metabolic niches in the rhizosphere microbiome: New tools and approaches to analyse metabolic mechanisms of plant-microbe nutrient exchange. J Exp Bot. 2018 Dec 20;: Authors: Jacoby RP, Kopriva S Abstract Plants nourish rhizospheric microbes via provision of carbon substrates, and microbiome composition is strongly influenced by metabolic phenomena such as niche differentiation, competitive exclusion, and cross-feeding. Despite intensive investigations of taxonomic breakdown in the root microbiome, there is relatively little biochemical knowledge of the metabolic niches occupied by microbial strains in the rhizosphere. Here, we summarise the new tools and approaches boosting our knowledge of the metabolic mechanisms that shape root microbiome composition. New studies have elucidated biochemical pathways that mediate root colonisation and pathogen suppression, and synthetic communities are emerging as a powerful tool to understand microbe-microbe interactions. Knowledge of root exudate composition is being advanced by new metabolomics methodologies, highlighting that specific exudate components can inhibit pathogen growth, and that certain metabolites can recruit mutualistic strains according to substrate uptake preferences. Microbial genomics is rapidly advancing, with large collections of isolated rhizosphere strains and mutant libraries giving new insights into the metabolic mechanisms of root colonisation. Exometabolomics is emerging as a powerful methodology to directly observe microbial uptake of root metabolites, and also for profiling microbial cross-feeding. Integrative studies using these resources should enable rapid advances, particularly when applied to standardised experimental setups and model synthetic communities. PMID: 30576534 [PubMed - as supplied by publisher]

Related Articles Red blood cell phenotype fidelity following glycerol cryopreservation optimized for research purposes. PLoS One. 2018;13(12):e0209201 Authors: Rogers SC, Dosier LB, McMahon TJ, Zhu H, Timm D, Zhang H, Herbert J, Atallah J, Palmer GM, Cook A, Ernst M, Prakash J, Terng M, Towfighi P, Doctor R, Said A, Joens MS, Fitzpatrick JAJ, Hanna G, Lin X, Reisz JA, Nemkov T, D'Alessandro A, Doctor A Abstract Intact red blood cells (RBCs) are required for phenotypic analyses. In order to allow separation (time and location) between subject encounter and sample analysis, we developed a research-specific RBC cryopreservation protocol and assessed its impact on data fidelity for key biochemical and physiological assays. RBCs drawn from healthy volunteers were aliquotted for immediate analysis or following glycerol-based cryopreservation, thawing, and deglycerolization. RBC phenotype was assessed by (1) scanning electron microscopy (SEM) imaging and standard morphometric RBC indices, (2) osmotic fragility, (3) deformability, (4) endothelial adhesion, (5) oxygen (O2) affinity, (6) ability to regulate hypoxic vasodilation, (7) nitric oxide (NO) content, (8) metabolomic phenotyping (at steady state, tracing with [1,2,3-13C3]glucose ± oxidative challenge with superoxide thermal source; SOTS-1), as well as in vivo quantification (following human to mouse RBC xenotransfusion) of (9) blood oxygenation content mapping and flow dynamics (velocity and adhesion). Our revised glycerolization protocol (40% v/v final) resulted in >98.5% RBC recovery following freezing (-80°C) and thawing (37°C), with no difference compared to the standard reported method (40% w/v final). Full deglycerolization (>99.9% glycerol removal) of 40% v/v final samples resulted in total cumulative lysis of ~8%, compared to ~12-15% with the standard method. The post cryopreservation/deglycerolization RBC phenotype was indistinguishable from that for fresh RBCs with regard to physical RBC parameters (morphology, volume, and density), osmotic fragility, deformability, endothelial adhesivity, O2 affinity, vasoregulation, metabolomics, and flow dynamics. These results indicate that RBC cryopreservation/deglycerolization in 40% v/v glycerol final does not significantly impact RBC phenotype (compared to fresh cells). PMID: 30576340 [PubMed - in process]

Related Articles Metabolomics and 16S rRNA sequencing of human colorectal cancers and adjacent mucosa. PLoS One. 2018;13(12):e0208584 Authors: Loke MF, Chua EG, Gan HM, Thulasi K, Wanyiri JW, Thevambiga I, Goh KL, Wong WF, Vadivelu J Abstract Colorectal cancer (CRC) is ranked the third most common cancer in human worldwide. However, the exact mechanisms of CRC are not well established. Furthermore, there may be differences between mechanisms of CRC in the Asian and in the Western populations. In the present study, we utilized a liquid chromatography-mass spectrometry (LC-MS) metabolomic approach supported by the 16S rRNA next-generation sequencing to investigate the functional and taxonomical differences between paired tumor and unaffected (normal) surgical biopsy tissues from 17 Malaysian patients. Metabolomic differences associated with steroid biosynthesis, terpenoid biosynthesis and bile metabolism could be attributed to microbiome differences between normal and tumor sites. The relative abundances of Anaerotruncus, Intestinimonas and Oscillibacter displayed significant relationships with both steroid biosynthesis and terpenoid and triterpenoid biosynthesis pathways. Metabolites involved in serotonergic synapse/ tryptophan metabolism (Serotonin and 5-Hydroxy-3-indoleacetic acid [5-HIAA]) were only detected in normal tissue samples. On the other hand, S-Adenosyl-L-homocysteine (SAH), a metabolite involves in methionine metabolism and methylation, was frequently increased in tumor relative to normal tissues. In conclusion, this study suggests that local microbiome dysbiosis may contribute to functional changes at the cancer sites. Results from the current study also contributed to the list of metabolites that are found to differ between normal and tumor sites in CRC and supported our quest for understanding the mechanisms of carcinogenesis. PMID: 30576312 [PubMed - in process]

Related Articles Vaporized E-Cigarette Liquids Induce Ion Transport Dysfunction in Airway Epithelia. Am J Respir Cell Mol Biol. 2018 Dec 21;: Authors: Lin VY, Fain MD, Jackson PL, Berryhill TF, Wilson LS, Mazur M, Barnes SJ, Blalock JE, Raju SV, Rowe SM Abstract Cigarette smoking is associated with chronic obstructive pulmonary disease and chronic bronchitis. Acquired ion transport abnormalities, including CFTR dysfunction, caused by cigarette smoking have been proposed as potential mechanisms for mucus obstruction in chronic bronchitis. Although popular and perceived to be safe, it remains unclear if e-cigarette use harms the airways via mechanisms altering ion transport. Here, we sought to determine if e-cigarette vapor, like cigarette smoke, had the potential to induce acquired CFTR dysfunction, and to what degree. Electrophysiologic methods demonstrated reduced chloride transport caused by vaporized e-cigarette liquid or vegetable glycerin at various exposures (30 min: 57.2% and 14.4% respectively, vs. control, p<0.0001), but not by unvaporized liquid (60 min: 17.6% vs. untreated), indicating that thermal degradation of these products is required to induce the observed defects. We also observed reduced ATP-dependent responses (-10.8±3.0 vs. -18.8±5.1 µA/cm2 control) and ENaC activity (95.8% reduction) in primary HBE cells after 5 min, suggesting exposures dramatically inhibit epithelial ion transport beyond CFTR, even without diminished transepithelial resistance or cytotoxicity. Vaporizing e-cigarette liquid produced reactive aldehydes including acrolein (shown to induce acquired CFTR dysfunction), as quantified by mass spectrometry, demonstrating that respiratory toxicants in cigarette smoke can also be found in e-cigarette vapor (30 min: air 224.5±15.99, unvaporized liquid 284.8±35.03, vapor 54,468±3908 ng/mL, p<0.0001). E-cigarettes can induce ion channel dysfunction in airway epithelial cells, partly through acrolein production. These findings indicate a heretofore unknown toxicity of e-cigarette use known to be associated with chronic bronchitis onset and progression, and COPD severity. PMID: 30576219 [PubMed - as supplied by publisher]

Related Articles Metabolic signature of a functional high-catechin tea after acute and sustained consumption in healthy volunteers through 1H NMR-based metabolomics analysis of urine. J Agric Food Chem. 2018 Dec 21;: Authors: Madrid-Gambin F, Garcia-Aloy M, Vázquez-Fresno R, Vegas-Lozano E, Sánchez-Pla A, Misawa K, Hase T, Shimotoyodome A, Andres-Lacueva C Abstract Functional tea beverages have emerged as a novel approach to achieving health benefits associated with tea. The use of metabolomics may improve the evaluation of their consumption and their effects. The current study aimed to explore the urinary signature of the exposure to a functional high-catechin tea (HCT) using untargeted NMR-based metabolomics. Ten volunteers participated in a crossover intervention study. Individuals consumed an HCT or a control beverage over a period of 28 days. Multilevel partial least squares discriminant analysis (ML-PLS-DA) was used for paired comparisons. A further crossover model was performed to assess the significant changes. The consumption of the HCT resulted in the excretion of theanine, epicatechin, pyrogallol sulfate, higher levels of 3-methyl-2-oxovalerate and succinate, as well as unknown compounds. In conclusion, the present work established novel urinary signatures of a functional drink. Such signatures may be potential biomarkers and/or reflect certain benefits of functional tea beverages. PMID: 30574780 [PubMed - as supplied by publisher]

Related Articles Comparative transcriptome and metabolome analysis suggests bottlenecks that limit seed and oil yields in transgenic Camelina sativa expressing diacylglycerol acyltransferase 1 and glycerol-3-phosphate dehydrogenase. Biotechnol Biofuels. 2018;11:335 Authors: Abdullah HM, Chhikara S, Akbari P, Schnell DJ, Pareek A, Dhankher OP Abstract Background: Camelina sativa has attracted much interest as alternative renewable resources for biodiesel, other oil-based industrial products and a source for edible oils. Its unique oil attributes attract research to engineering new varieties of improved oil quantity and quality. The overexpression of enzymes catalyzing the synthesis of the glycerol backbone and the sequential conjugation of fatty acids into this backbone is a promising approach for increasing the levels of triacylglycerol (TAG). In a previous study, we co-expressed the diacylglycerol acyltransferase (DGAT1) and glycerol-3-phosphate dehydrogenase (GPD1), involved in TAG metabolism, in Camelina seeds. Transgenic plants exhibited a higher-percentage seed oil content, a greater seed mass, and overall improved seed and oil yields relative to wild-type plants. To further increase seed oil content in Camelina, we utilized metabolite profiling, in conjunction with transcriptome profiling during seed development to examine potential rate-limiting step(s) in the production of building blocks for TAG biosynthesis. Results: Transcriptomic analysis revealed approximately 2518 and 3136 transcripts differentially regulated at significant levels in DGAT1 and GPD1 transgenics, respectively. These transcripts were found to be involved in various functional categories, including alternative metabolic routes in fatty acid synthesis, TAG assembly, and TAG degradation. We quantified the relative contents of over 240 metabolites. Our results indicate major metabolic switches in transgenic seeds associated with significant changes in the levels of glycerolipids, amino acids, sugars, and organic acids, especially the TCA cycle and glycolysis intermediates. Conclusions: From the transcriptomic and metabolomic analysis of DGAT1, GPD1 and DGAT1 + GPD1 expressing lines of C. sativa, we conclude that TAG production is limited by (1) utilization of fixed carbon from the source tissues supported by the increase in glycolysis pathway metabolites and decreased transcripts levels of transcription factors controlling fatty acids synthesis; (2) TAG accumulation is limited by the activity of lipases/hydrolases that hydrolyze TAG pool supported by the increase in free fatty acids and monoacylglycerols. This comparative transcriptomics and metabolomics approach is useful in understanding the regulation of TAG biosynthesis, identifying bottlenecks, and the corresponding genes controlling these pathways identified as limitations, for generating Camelina varieties with improved seed and oil yields. PMID: 30574188 [PubMed]

Related Articles Variability of Two Metabolomic Platforms in CKD. Clin J Am Soc Nephrol. 2018 Dec 20;: Authors: Rhee EP, Waikar SS, Rebholz CM, Zheng Z, Perichon R, Clish CB, Evans AM, Avila J, Denburg MR, Anderson AH, Vasan RS, Feldman HI, Kimmel PL, Coresh J, CKD Biomarkers Consortium Abstract BACKGROUND AND OBJECTIVES: Nontargeted metabolomics can measure thousands of low-molecular-weight biochemicals, but important gaps limit its utility for biomarker discovery in CKD. These include the need to characterize technical and intraperson analyte variation, to pool data across platforms, and to outline analyte relationships with eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma samples from 49 individuals with CKD (eGFR<60 ml/min per 1.73 m2 and/or ≥1 g proteinuria) were examined from two study visits; 20 samples were repeated as blind replicates. To enable comparison across two nontargeted platforms, samples were profiled at Metabolon and the Broad Institute. RESULTS: The Metabolon platform reported 837 known metabolites and 483 unnamed compounds (selected from 44,953 unknown ion features). The Broad Institute platform reported 594 known metabolites and 26,106 unknown ion features. Median coefficients of variation (CVs) across blind replicates were 14.6% (Metabolon) and 6.3% (Broad Institute) for known metabolites, and 18.9% for (Metabolon) unnamed compounds and 24.5% for (Broad Institute) unknown ion features. Median CVs for day-to-day variability were 29.0% (Metabolon) and 24.9% (Broad Institute) for known metabolites, and 41.8% for (Metabolon) unnamed compounds and 40.9% for (Broad Institute) unknown ion features. A total of 381 known metabolites were shared across platforms (median correlation 0.89). Many metabolites were negatively correlated with eGFR at P<0.05, including 35.7% (Metabolon) and 18.9% (Broad Institute) of known metabolites. CONCLUSIONS: Nontargeted metabolomics quantifies >1000 analytes with low technical CVs, and agreement for overlapping metabolites across two leading platforms is excellent. Many metabolites demonstrate substantial intraperson variation and correlation with eGFR. PMID: 30573658 [PubMed - as supplied by publisher]

Related Articles Activation of peroxisome proliferator-activated receptors α and δ synergizes with inflammatory signals to enhance adoptive cell therapy. Cancer Res. 2018 Dec 20;: Authors: Saibil SD, St Paul M, Laister RC, Garcia-Batres CR, Israni-Winger K, Elford AR, Grimshaw N, Robert-Tissot C, Roy DG, Jones RG, Nguyen LT, Ohashi PS Abstract Memory CD8+ T cells (Tmem) are superior mediators of adoptive cell therapy (ACT) compared to effector CD8+ T cells (Teff) due to increased persistence in vivo. Underpinning Tmem survival is a shift in cellular metabolism away from aerobic glycolysis towards fatty acid oxidation (FAO). Here we investigated the impact of the peroxisome proliferator-activated receptor (PPAR) agonist GW501516 (GW), an agent known to boost FAO in other tissues, on CD8+ T cell metabolism, function, and efficacy in a murine ACT model. Via activation of both PPARα and PPARδ/β, GW treatment increased expression of carnitine palmitoyl transferase 1a (CPT1a), the rate-limiting enzyme of FAO, in activated CD8+ T cells. Using a metabolomics approach, we demonstrated that GW increased the abundance of multiple different acylcarnitines, consistent with enhanced FAO. T cells activated in the presence of GW and inflammatory signals, either mature dendritic cells (DC) or IL-12, also demonstrated enhanced production of interferon-γ and expression of T-bet. Despite high expression of T-bet, a characteristic of short-lived effector cells, GW-treated cells demonstrated enhanced persistence in vivo and superior efficacy in a model of ACT. Collectively, these data identify combined PPARα and PPARδ/β agonists as attractive candidates for further studies and rapid translation into clinical trials of ACT. PMID: 30573521 [PubMed - as supplied by publisher]

Related Articles Saccharomyces cerevisiae morphological changes and cytokinesis arrest elicited by hypoxia during scale-up for production of therapeutic recombinant proteins. Microb Cell Fact. 2018 Dec 20;17(1):195 Authors: Aon JC, Tecson RC, Loladze V Abstract BACKGROUND: Scaling up of bioprocesses represents a crucial step in the industrial production of biologicals. However, our knowledge about the impact of scale-up on the organism's physiology and function is still incomplete. Our previous studies have suggested the existence of morphological changes during the scale-up of a yeast (Saccharomyces cerevisiae) fermentation process as inferred from the volume fraction occupied by yeast cells and exometabolomics analyses. In the current study, we noticed cell morphology changes during scale-up of a yeast fermentation process from bench (10 L) to industrial scale (10,000 L). We hypothesized that hypoxia observed during scale-up partially impaired the availability of N-acetyl-glucosamine, a precursor of chitin synthesis, a key polysaccharide component of yeast mother-daughter neck formation. RESULTS: Using a combination of flow cytometry with two high throughput cell imaging technologies, Vi-CELL and Flow Imaging, we found changes in the distribution of cell size and morphology as a function of process duration at the industrial scale of the production process. At the end of run, concomitantly with lowest levels of dissolved oxygen (DO), we detected an increase in cell subpopulations exhibiting low aspect ratio corresponding to morphologies exhibited by large-single-budded and multi-budded cells, reflecting incomplete cytokinesis at the M phase of the yeast mitotic cycle. Metabolomics from the intracellular milieu pointed to an impaired supply of precursors for chitin biosynthesis likely affecting the septum formation between mother and daughter and cytokinesis. Inducing hypoxia at the 10 L bench scale by varying DO levels, confirmed the existence and impact of hypoxic conditions on yeast cell size and morphology observed at the industrial scale. CONCLUSIONS: We conclude that the observed increments in wet cell weight at the industrial scale correspond to morphological changes characterized by the large diameter and low aspect ratio exhibited by cell subpopulations comprising large single-budded and multi-budded cells. These changes are consistent with impairment of cytokinesis triggered by hypoxia as indicated by experiments mimicking this condition at DO 5% and 10 L scale. Mechanistically, hypoxia impairs N-acetyl-glucosamine availability, a key precursor of chitin synthesis. PMID: 30572885 [PubMed - in process]

Related Articles New frontiers in precision medicine for sepsis-induced immunoparalysis. Expert Rev Clin Immunol. 2018 Dec 20;: Authors: Bruse N, Leijte GP, Pickkers P, Kox M Abstract INTRODUCTION: In the last decade, the sepsis research field has shifted focus from targeting hyperinflammation to reversing sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis is very heterogeneous: the magnitude and the nature of the underlying immune defects differ considerably between patients, but also within individuals over time. Therefore, a "one-treatment-fits-all" strategy for sepsis-induced immunoparalysis is bound to fail, and an individualized "precision medicine" approach is required. Such a strategy is nevertheless hampered by the unsuitability of the currently available markers to identify the many immune defects that can manifest in individual patients. Areas covered: We describe the currently available markers for sepsis-induced immunoparalysis and limitations pertaining to their use. Furthermore, future prospects and caveats are discussed, focusing on "omics" approaches: genomics, transcriptomics, epigenomics, and metabolomics. Finally, we present a contemporary overview of adjuvant immunostimulatory therapies. Expert opinion: The integration of multiple omics techniques offers a systems biology approach which can yield biomarker profiles that accurately and comprehensively gauge the extent and nature of sepsis-induced immunoparalysis. We expect this development to be instrumental in facilitating precision medicine for sepsis-induced immunoparalysis, consisting of the application of targeted immunostimulatory therapies and follow-up measurements to monitor the response to treatment and to titrate or adjust medication. PMID: 30572728 [PubMed - as supplied by publisher]

Related Articles Carbon Consumption Patterns of Microbial Communities Associated with Peltigera Lichens from a Chilean Temperate Forest. Molecules. 2018 Oct 24;23(11): Authors: Almendras K, Leiva D, Carú M, Orlando J Abstract Lichens are a symbiotic association between a fungus and a green alga or a cyanobacterium, or both. They can grow in practically any terrestrial environment and play crucial roles in ecosystems, such as assisting in soil formation and degrading soil organic matter. In their thalli, they can host a wide diversity of non-photoautotrophic microorganisms, including bacteria, which play important functions and are considered key components of the lichens. In this work, using the BioLog® EcoPlate system, we studied the consumption kinetics of different carbon-sources by microbial communities associated with the thallus and the substrate of Peltigera lichens growing in a Chilean temperate rain forest dominated by Nothofagus pumilio. Based on the similarity of the consumption of 31 carbon-sources, three groups were formed. Among them, one group clustered the microbial metabolic profiles of almost all the substrates from one of the sampling sites, which exhibited the highest levels of consumption of the carbon-sources, and another group gathered the microbial metabolic profiles from the lichen thalli with the most abundant mycobiont haplotypes. These results suggest that the lichen thallus has a higher impact on the metabolism of its microbiome than on the microbial community of its substrate, with the latter being more diverse in terms of the metabolized sources and whose activity level is probably related to the availability of soil nutrients. However, although significant differences were detected in the microbial consumption of several carbon-sources when comparing the lichen thallus and the underlying substrate, d-mannitol, l-asparagine, and l-serine were intensively metabolized by both communities, suggesting that they share some microbial groups. Likewise, some communities showed high consumption of 2-hydroxybenzoic acid, d-galacturonic acid, and itaconic acid; these could serve as suitable sources of microorganisms as bioresources of novel bioactive compounds with biotechnological applications. PMID: 30355963 [PubMed - indexed for MEDLINE]

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 2018/12/21PubMed 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.