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18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/11/24PubMed 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.

Lung inflammation and disease: A perspective on microbial homeostasis and metabolism. IUBMB Life. 2018 Nov 22;: Authors: Mendez R, Banerjee S, Bhattacharya SK, Banerjee S Abstract It is now well appreciated that the human microbiome plays a significant role in a number of processes in the body, significantly affecting its metabolic, inflammatory, and immune homeostasis. Recent research has revealed that almost every mucosal surface in the human body is associated with a resident commensal microbiome of its own. While the gut microbiome and its role in regulation of host metabolism along with its alteration in a disease state has been well studied, there is a lacuna in understanding the resident microbiota of other mucosal surfaces. Among these, the scientific information on the role of lung microbiota in pulmonary diseases is currently severely limited. Historically, lungs have been considered to be sterile and lung diseases have only been studied in the context of bacterial pathogenesis. Recently however, studies have revealed a resilient microbiome in the upper and lower respiratory tracts and there is increased evidence on its central role in respiratory diseases. Knowledge of lung microbiome and its metabolic fallout (local and systemic) is still in its nascent stages and attracting immense interest in recent times. In this review, we will provide a perspective on lung-associated metabolic disorders defined for lung diseases (e.g., chronic obstructive pulmonary disease, asthma, and respiratory depression due to infection) and correlate it with lung microbial perturbation. Such perturbations may be due to altered biochemical or metabolic stress as well. Finally, we will draw evidence from microbiome and classical microbiology literature to demonstrate how specific lung morbidities associate with specific metabolic characteristics of the disease, and with the role of microbiome in this context. © 2018 IUBMB Life, 1-14, 2018. PMID: 30466159 [PubMed - as supplied by publisher]

Improving liquid chromatography-tandem mass spectrometry determination of polycarboxylic acids in human urine by chemical derivatization. Comparison of o-benzyl hydroxylamine and 2-picolyl amine. J Pharm Biomed Anal. 2018 Nov 03;164:382-394 Authors: Gomez-Gomez A, Soldevila A, Pizarro N, Andreu-Fernandez V, Pozo OJ Abstract Due to its high sensitivity and specificity, liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) could be considered as the gold-standard in targeted metabolomics. Although LC-MS/MS allows for the direct detection of a large number of molecules, the proper quantification of highly polar compounds such as poly-carboxylic acids in complex matrices like urine is still a challenge. Chemical derivatization offers a suitable way to improve chromatographic behavior and sensitivity for these compounds. Several derivatizing agents have been proposed for the LC-MS/MS determination of carboxylic acids but studies dealing with their comparison in challenging scenarios are scarce. Here we present the evaluation of two different derivatization agents; o-benzylhydroxyl amine (oBHA) and 2-picolyl amine (2-PA); for the quantification of the (poly)-carboxylic acids belonging to the tricarboxylic acid cycle in urine. The suitability of both derivatizating agents was compared by validation of the two approaches. Derivatization with oBHA showed important advantages against 2-PA derivatization such as (i) providing better sensitivity, (ii) more stable derivatives and (iii) allowing for the proper validation of a larger number of analytes. Moreover, while 2-PA derivatization failed in the determination of the target analytes in some stored urine samples, oBHA derivatization successfully allowed for their appropriate determination in the same samples. A comparison between the concentrations obtained using oBHA derivatization and those provided by an external laboratory using UV and GC-MS detection revealed a satisfactory agreement between both results. Additionally, the concentrations obtained by the oBHA method for a set of 38 urines are in agreement with those previously reported in the literature. As a conclusion, our results show that the use of oBHA is preferred against 2-PA for the detection and quantification of (poly)-carboxylic acids in urine. PMID: 30466023 [PubMed - as supplied by publisher]

Herb-drug interaction: A case study of effects and involved mechanisms of cisplatin on the pharmacokinetics of ginsenoside Rb1 in tumor-bearing mice. Biomed Pharmacother. 2018 Nov 19;110:95-104 Authors: Zhou J, Wu J, Wu CY, Long F, Shen H, Zhang W, Li SL Abstract Ginseng is often prescribed together with cisplatin for treatment of cancer, but the interaction between ginseng and cisplatin is still unknown. This study employed ginsenoside Rb1 (Rb1), one of the major components in ginseng, to explore the effects and involved mechanisms of cisplatin on the pharmacokinetics of ginseng. The effects of cisplatin on the pharmacokinetics of Rb1 and its bioactive metabolites Rd, Rg3, and F2 were investigated by using A549-bearing mice with and without cisplatin intervention. Our data showed that cisplatin could significantly decrease the AUC(0-t) and Cmax of Rd, Rg3, and F2, except Rb1. To evaluate the involved mechanisms, feces and intestinal mucosa were collected to explore the effects of cisplatin on the gut metabolism of Rb1 in vitro; meanwhile, Caco-2 cell model and small intestine histological characters were examined to evaluate the effects of cisplatin on the gut absorptive areas and permeability. The mechanisms involved may be mainly related to the comprehensive contributions of inhibited intestinal bacteria and mucosa metabolisms, narrowed intestinal absorptive area, increased efflux ratio of intestinal absorption and enhanced intestinal permeability. All these findings suggested that the dosage of ginseng traditionally used for health protection should be adjusted when it was prescribed together with cisplatin in the treatment of cancer. PMID: 30466007 [PubMed - as supplied by publisher]

NMR based metabolomics: An exquisite and facile method for evaluating therapeutic efficacy and screening drug toxicity. Curr Top Med Chem. 2018 Nov 20;: Authors: Guleria A, Kumar A, Kumar U, Raj R, Kumar D Abstract Metabolomics is an analytical approach to metabolism and involves quantitative and comparative analysis of low-molecular-weight metabolites in body fluids or cellular/tissues extracts. Owing to its ability to reveal disease-specific metabolic patterns or metabolic changes produced in response to a therapeutic intervention; it is gaining widespread applications virtually in all aspects of biomedical and pharmaceutical research pertaining to human healthcare management. It has also started playing a strategic role in pharmacological and toxicological research for evaluating therapeutic efficacy/safety of promising drug candidates either alone or in conjunction with other omics tools such as genomics, transcriptomics and proteomics. The metabolic profiling capabilities of nuclear magnetic resonance (NMR) spectroscopy along with pattern recognition methods have successfully been applied for identifying diagnostic panel of biomarkers, evaluating drug efficacy/safety, screening toxicity and disease mechanism. Particularly, the interest in applying NMR-based metabolomics for the assessment of therapeutic efficacy and safety is increasing among drug researchers and drug regulators owing to its non-destructive, non-selective and minimal sample preparation requirement. On top of this, it offers the potential for high-throughput (i.e. >100 samples a day is attainable) and provides highly reproducible results. In this review, we will discuss some of the recent developments related to NMR based metabolomics followed by some recent literature examples to highlight its potential in (a) the evaluation of therapeutic efficacy and safety of lead discovery compounds, (b) monitoring disease status and recovery after treatment and (c) identification and evaluation of biomarkers of systemic/organ-specific toxicity. Additionally, the review will also highlight its role to facilitate clinical trial testing and improve post-approval drug monitoring. PMID: 30465509 [PubMed - as supplied by publisher]

Related Articles Gold Standard Assessment of Immunogenic Cell Death in Oncological Mouse Models. Methods Mol Biol. 2019;1884:297-315 Authors: Humeau J, Lévesque S, Kroemer G, Pol JG Abstract The efficacy of cancer therapies strongly relies on their ability to reinstate cancer immunosurveillance. Numerous biomedical approaches with immunotherapeutic activity have been developed to reeducate the host immune system to detect and clear tumor cells. Cytotoxicants have been primarily designed to slow down malignant cell proliferation and to induce programmed cell death. Some cytotoxic stimuli are able to activate a particular type of apoptosis, which is referred to as immunogenic cell death (ICD), that de facto convert cancer cells into their own vaccine. This effect ultimately facilitates the establishment of an antitumor immune response that potentially annihilates spared malignant cells, as well as an immune memory that prevents cancer recurrence. Based on the characteristic hallmarks of ICD, protocols have been developed to validate ICD induction in vitro, ex vivo, and in vivo. These methods may contribute to identify novel ICD inducers and to design multimodal regimens with superior therapeutic efficacy. Moreover, their translation into clinical research could have prognostic or predictive value. This chapter will introduce the "gold standard" protocol for the in vivo assessment of ICD in mice. The procedure relies on vaccination with treated cancer cells, followed by rechallenge with living entities of the same type, in syngeneic immunocompetent animals. PMID: 30465212 [PubMed - in process]

Related Articles Metabolomics of Breast Milk: The Importance of Phenotypes. Metabolites. 2018 Nov 20;8(4): Authors: Dessì A, Briana D, Corbu S, Gavrili S, Cesare Marincola F, Georgantzi S, Pintus R, Fanos V, Malamitsi-Puchner A Abstract Breast milk is the gold standard of nutrition for newborns. Its composition is tailored to the nutritional needs of the infant and varies between mothers. In recent years, several bioactive molecules have been discovered in addition to the main nutrients, such as multipotent stem cells, hormones, immunoglobulins, and bacteria. Furthermore, the human milk oligosaccharides (HMOs) seem to exert several important protective biological functions. According to the HMOs' composition, breast milk can be classified as a secretory or non-secretory phenotype. In our study, we investigated the metabolome of milk collected from 58 mothers that delivered neonates at term, that were appropriate, small or large for gestational age, by performing nuclear magnetic resonance spectroscopy (¹H-NMR). From the data analysis, two groups were distinguished based on their different types of oligosaccharides, and classified according the mother phenotype: secretory and non-secretory. This information is of major importance given the different biological function of the different HMOs, such as immune-modulation and protection against disease. This would allow us to predict whether the neonate would be, for instance, more prone to developing certain diseases, and to tailor her or his nutrition to fit their needs perfectly and pave the way to a personalized nutrition. PMID: 30463323 [PubMed]

Related Articles Molecular Fingerprints of Iron Parameters among a Population-Based Sample. Nutrients. 2018 Nov 19;10(11): Authors: Kaul A, Masuch A, Budde K, Kastenmüller G, Artati A, Adamski J, Völzke H, Nauck M, Friedrich N, Pietzner M Abstract Iron deficiency is the most frequent deficiency disease and parameters of iron metabolism appear to be linked to major metabolic and cardiovascular diseases. We screened a large set of small molecules in plasma for associations with iron status among apparently healthy subjects to elucidate subclinical profiles which may provide a link between iron status and onset of diseases. Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined 613 plasma metabolites and lipoprotein subfractions among 820 apparently healthy individuals. Associations between ferritin, transferrin, haemoglobin and myoglobin and metabolite levels were tested by sex-specific linear regression analyses controlling for common confounders. Far more significant associations in women (82 out of 102) compared to men became obvious. The majority of the metabolites associated with serum ferritin and haemoglobin in women comprising fatty acid species, branched-chain amino acid catabolites and catabolites of heme. The latter was also obvious among men. Positive associations between serum transferrin and VLDL and IDL particle measures seen in women were observed in men with respect to serum ferritin. We observed a sexual-dimorphic fingerprint of surrogates of iron metabolism which may provide a link for the associations between those parameters and major metabolic and cardiovascular disease. PMID: 30463274 [PubMed - in process]

Related Articles Mass spectrometry-based metabolomics reveals the mechanism of ambient fine particulate matter and its components on energy metabolic reprogramming in BEAS-2B cells. Sci Total Environ. 2019 Feb 15;651(Pt 2):3139-3150 Authors: Song Y, Li R, Zhang Y, Wei J, Chen W, Chung CKA, Cai Z Abstract Exposure to airborne fine particulate matter (PM2.5) is associated with various adverse effects. However, the molecular mechanism involved in PM2.5-elicited energy metabolic reprogramming and the toxic chemical determinants within PM2.5 are not well elucidated. In this study, nontargeted and targeted metabolomics research were conducted to investigate the overall metabolic changes and relevant toxicological pathways caused by Taiyuan winter total PM2.5 and its water soluble and organic soluble fractions in human lung bronchial epithelial cells (BEAS-2B). The results showed that significant metabolome alterations in BEAS-2B cells were observed after the exposure of total PM2.5 and its organic soluble fraction. Purine metabolism, arginine and proline metabolism, glutathione (GSH) metabolism, tricarboxylic acid (TCA) cycle and glycolysis were mainly affected. Along with a significant increase of reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), obvious metabolic phenotype remodeling from oxidative phosphorylation to glycolysis was found in BEAS-2B cells treated with total PM2.5 and its organic soluble fraction. Compared with water soluble fraction, organic soluble fraction was found to play the dominant role in PM2.5 toxicity. Our study provided novel insights into the mechanism of PM2.5-elicited toxicity. PMID: 30463164 [PubMed - in process]

Related Articles Novel insight into the role of withering process in characteristic flavor formation of teas using transcriptome analysis and metabolite profiling. Food Chem. 2019 Jan 30;272:313-322 Authors: Wang Y, Zheng PC, Liu PP, Song XW, Guo F, Li YY, Ni DJ, Jiang CJ Abstract Withering is an indispensable process for improving flavors in green, black and white teas during their manufacturing. The effects of the withering process on the formation of tea flavors were investigated using transcriptome and metabolite profiling in withered tea leaves. A total of 3268, 23,282 and 25,185 differentially expressed genes (DEGs) were identified at 3 h (68%, water content), 12 h (61%) and 24 h (48%) of the withering process, respectively. The DEGs, involved in flavonoid biosynthesis were significantly downregulated, which could be correlated with the reduction of catechins. Enhancement of terpenoids and alpha-linolenic acid metabolism could trigger an increase in the total content and number of volatiles. The increase in free amino acid-content could be related to 261 DEGs. Our study suggests that dehydration stress during withering induced significant changes in the gene transcription and content of the tea flavor compounds, which promoted the special flavors in various teas. PMID: 30309549 [PubMed - indexed for MEDLINE]

Related Articles Metabolomics of thyroid nodules and the future. Arch Endocrinol Metab. 2018 Oct;62(5):493-494 Authors: Gomes RLE, Gebrim EMMS PMID: 30462800 [PubMed - in process]

Related Articles NMR-based metabolomics to select a surgical method for treating papillary thyroid carcinoma. Clinics (Sao Paulo). 2018 Nov 14;73:e333 Authors: Wang B, Zhang LY, Wang SS, Yang YH, Zhao WX Abstract OBJECTIVE: This study aims to investigate differences in the metabolomic profiles of patients who received different surgeries for papillary thyroid carcinoma (PTC). METHODS: Two surgical methods, i.e., unilateral and total thyroidectomy, were employed according to different disease conditions. Sera from patients who were treated with levothyroxine sodium tablets before and after surgery was analyzed with a Bruker 500 Hz nuclear magnetic resonance (NMR) spectrometer. Data were analyzed via principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA) with SIMCA-P+ 11.0 software, and metabolites were obtained and compared. The first and second principal components were selected from PCA, PLS-DA, and orthogonal partial least squares discriminate analysis (OPLS-DA). A p-value less than 0.05 was considered statistically significant. RESULTS: There were significant differences in serum metabolomics before and after surgery. Compared with unilateral thyroidectomy, total thyroidectomy reversed some highly increased metabolite levels (e.g., taurine and betaine). More significant variations in abnormal metabolites were noted after total thyroidectomy than after unilateral thyroidectomy (e.g., alanine, choline, hippurate, and formic acid). CONCLUSIONS: The choice of surgical method for PTC patients should be based not only on the tumor condition but also on the potential consequences of metabolic variations. Total thyroidectomy reversed some increased metabolite levels but led to accumulation of some other metabolites due to the loss of thyroid function; thus, metabolic disturbances caused by thyroid hormone deficiency should be prevented in advance. PMID: 30462753 [PubMed - in process]

Related Articles Metabolic remodeling of glucose, fatty acid and redox pathways in the heart of type 2 diabetic mice. J Physiol. 2018 Nov 21;: Authors: Cortassa S, Caceres V, Tocchetti CG, Bernier M, de Cabo R, Paolocci N, Sollott SJ, Aon MA Abstract KEY POINTS: Hearts from type 2 diabetic animals display perturbations in excitation-contraction coupling, impairing myocyte contractility and delaying relaxation, along with altered substrate consumption patterns. Under high glucose and β-adrenergic stimulation conditions, palmitate can, at least in part, offset left ventricle (LV) dysfunction in hearts from diabetic mice improving contractility and relaxation while restoring coronary perfusion pressure. Fluxome calculations of central catabolism in diabetic hearts show that, in presence of palmitate, there is a metabolic remodeling involving tricarboxylic acid cycle, polyol and pentose phosphate pathways, leading to improved redox balance in cytoplasmic and mitochondrial compartments. Under high glucose and increased energy demand, the metabolic/fluxomic re-direction leading to restored redox balance imparted by palmitate helps explain maintained LV function and may contribute to design novel therapeutic approaches to prevent cardiac dysfunction in diabetic patients. ABSTRACT: Type-2 diabetes (T2DM) leads to reduced myocardial performance, and eventually heart failure. Excessive accumulation of lipids and glucose are central to T2DM cardiomyopathy. Previous data showed that palmitate (Palm) or glutathione preserved heart mitochondrial energy/redox balance under excess glucose rescuing β-adrenergic-stimulated cardiac excitation-contraction coupling. However, the mechanisms underlying the accompanying improved contractile performance have been largely ignored. Herein we explore in intact heart under substrate excess the metabolic remodeling associated with cardiac function in diabetic db/db mice subjected to stress given by β-adrenergic stimulation with isoproterenol and high-glucose compared to their nondiabetic controls (+/+, WT) under euglycemic conditions. When perfused with Palm, T2DM hearts exhibit improved contractility/relaxation compared to WT, accompanied by extensive metabolic remodeling as demonstrated by metabolomics-fluxomics combined with bioinformatics and computational modeling. The T2DM heart metabolome showed significant differences in the abundance of metabolites in pathways related to glucose, lipids, and redox metabolism. Using a validated computational model of heart's central catabolism, comprising glucose and fatty acid (FA) oxidation in cytoplasmic and mitochondrial compartments, we estimated that fluxes through glucose degradation pathways are ∼2-fold lower in heart from T2DM vs. WT under all conditions studied. Palm addition elicits improvement of the redox status via enhanced β-oxidation and decreased glucose uptake, leading to flux-redirection away from redox-consuming pathways (e.g., polyol) while maintaining the flux through redox-generating pathways together with glucose-FA "shared fueling" of oxidative phosphorylation. Thus, available FAs such as Palm may help improve function via enhanced redox balance in T2DM hearts during peaks of hyperglycemia and increased workload. Sonia Cortassa has a PhD in Chemical Sciences from the Universidad Nacional de Córdoba, Argentina, country where she held research and teaching positions at Universidad Nacional de Tucumán and Consejo Nacional Investigaciones Científicas y Técnicas (CONICET). In the United States of America, she continued her research at the Johns Hopkins University and, at present, at the Laboratory of Cardiovascular Sciences/National Institute on Aging/NIH. Her field of research is Physiology, Bioenergetics, with expertise in Computational modeling of metabolic networks. She believes that quantitative Systems Biology approaches represent a real opportunity to contribute to the understanding of human body function in health and disease. This article is protected by copyright. All rights reserved. PMID: 30462352 [PubMed - as supplied by publisher]

Related Articles Heterocyclic electrophiles as new MurA inhibitors. Arch Pharm (Weinheim). 2018 Nov 21;: Authors: Keeley A, Ábrányi-Balogh P, Hrast M, Imre T, Ilaš J, Gobec S, Keserű GM Abstract An electrophilic fragment library of small heterocycles was developed and characterized in the surrogate GSH-reactivity assay and aqueous stability test that revealed their potential as covalent warheads. Screening the library against MurA from Staphylococcus aureus (MurASA ) and Escherichia coli (MurAEC ) identified heterocyclic fragments with significant inhibitory potency. The validated heterocyclic warhead library might be useful for developing targeted covalent inhibitors for other targets of interest with a new design strategy incorporating heterocyclic electrophiles as warheads. PMID: 30461051 [PubMed - as supplied by publisher]

Related Articles Eco-Metabolomics and Metabolic Modeling: Making the Leap From Model Systems in the Lab to Native Populations in the Field. Front Plant Sci. 2018;9:1556 Authors: Nagler M, Nägele T, Gilli C, Fragner L, Korte A, Platzer A, Farlow A, Nordborg M, Weckwerth W Abstract Experimental high-throughput analysis of molecular networks is a central approach to characterize the adaptation of plant metabolism to the environment. However, recent studies have demonstrated that it is hardly possible to predict in situ metabolic phenotypes from experiments under controlled conditions, such as growth chambers or greenhouses. This is particularly due to the high molecular variance of in situ samples induced by environmental fluctuations. An approach of functional metabolome interpretation of field samples would be desirable in order to be able to identify and trace back the impact of environmental changes on plant metabolism. To test the applicability of metabolomics studies for a characterization of plant populations in the field, we have identified and analyzed in situ samples of nearby grown natural populations of Arabidopsis thaliana in Austria. A. thaliana is the primary molecular biological model system in plant biology with one of the best functionally annotated genomes representing a reference system for all other plant genome projects. The genomes of these novel natural populations were sequenced and phylogenetically compared to a comprehensive genome database of A. thaliana ecotypes. Experimental results on primary and secondary metabolite profiling and genotypic variation were functionally integrated by a data mining strategy, which combines statistical output of metabolomics data with genome-derived biochemical pathway reconstruction and metabolic modeling. Correlations of biochemical model predictions and population-specific genetic variation indicated varying strategies of metabolic regulation on a population level which enabled the direct comparison, differentiation, and prediction of metabolic adaptation of the same species to different habitats. These differences were most pronounced at organic and amino acid metabolism as well as at the interface of primary and secondary metabolism and allowed for the direct classification of population-specific metabolic phenotypes within geographically contiguous sampling sites. PMID: 30459786 [PubMed]

Related Articles A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking. Front Endocrinol (Lausanne). 2018;9:606 Authors: Cox NJ, Luo PM, Smith TJ, Bisnett BJ, Soderblom EJ, Boyce M Abstract O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants. In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration. Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it. However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress. Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field. To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins. In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways. Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking. Moreover, we detected 11 O-GlcNAc moieties on COPγ1 and found that this modification is reduced by a model secretory stress that halts COPI trafficking. Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways. More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts. PMID: 30459710 [PubMed]

Related Articles Zebrafish Larvae Are a Suitable Model to Investigate the Metabolic Phenotype of Drug-Induced Renal Tubular Injury. Front Pharmacol. 2018;9:1193 Authors: Morello J, Derks RJE, Lopes SS, Steenvoorden E, Monteiro EC, Mayboroda OA, Pereira SA Abstract Prevention and treatment of drug-induced renal injury (DIRI) rely on the availability of sensitive and specific biomarkers of early kidney injury and predictive animal models of human pathophysiology. This study aimed to evaluate the potential of zebrafish larvae as translational model in metabolic profiling of DIRI. Zebrafish larvae were exposed to the lethal concentration for 10% of the larvae (LC10) or ½ LC10 of gentamicin, paracetamol and tenofovir as tenofovir disoproxil fumarate (TDF) and tenofovir (TFV). Metabolites were extracted from whole larvae and analyzed by liquid chromatography-mass spectrometry. Principal component analysis showed that drug exposition to the LC10 of paracetamol, TFV, and TDF was the main source of the variance of the data. To identify the metabolites responsible for the toxic effects of the drugs, partial least squares discriminant analyses were built between the LC10 and ½ LC10 for each drug. Features with variable importance in projection> 1.0 were selected and Venn diagrams were built to differentiate between the common and drug specific metabolites of DIRI. Creatine, tyrosine, glutamine, guanosine, hypoxanthine were identified as common metabolites, adenosine and tryptophan as paracetamol-specific and xanthine and oxidized glutathione as tenofovir-specific. Those metabolic changes can be associated with alterations in energy metabolism, xenobiotic detoxification and protein catabolism, all described in the human pathophysiology of DIRI. Thus, zebrafish proved to be a suitable model to characterize the metabolic changes associated with DIRI. This information can be useful to early diagnose DIRI and to improve our knowledge on the mechanisms of DIRI. PMID: 30459607 [PubMed]

Related Articles Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD. Sci Rep. 2018 Nov 20;8(1):17132 Authors: Cruickshank-Quinn CI, Jacobson S, Hughes G, Powell RL, Petrache I, Kechris K, Bowler R, Reisdorph N Abstract Chronic obstructive pulmonary disease (COPD) comprises multiple phenotypes such as airflow obstruction, emphysema, and frequent episodes of acute worsening of respiratory symptoms, known as exacerbations. The goal of this pilot study was to test the usefulness of unbiased metabolomics and transcriptomics approaches to delineate biological pathways associated with COPD phenotypes and outcomes. Blood was collected from 149 current or former smokers with or without COPD and separated into peripheral blood mononuclear cells (PBMC) and plasma. PBMCs and plasma were analyzed using microarray and liquid chromatography mass spectrometry, respectively. Statistically significant transcripts and compounds were mapped to pathways using IMPaLA. Results showed that glycerophospholipid metabolism was associated with worse airflow obstruction and more COPD exacerbations. Sphingolipid metabolism was associated with worse lung function outcomes and exacerbation severity requiring hospitalizations. The strongest associations between a pathway and a certain COPD outcome were: fat digestion and absorption and T cell receptor signaling with lung function outcomes; antigen processing with exacerbation frequency; arginine and proline metabolism with exacerbation severity; and oxidative phosphorylation with emphysema. Overlaying transcriptomic and metabolomics datasets across pathways enabled outcome and phenotypic differences to be determined. Findings are relevant for identifying molecular targets for animal intervention studies and early intervention markers in human cohorts. PMID: 30459441 [PubMed - in process]

Related Articles Comparison of Effects of Diet on Mammary Cancer: Efficacy of Various Preventive Agents and Metabolomic Changes of Different Diets and Agents. Cancer Prev Res (Phila). 2018 Nov 20;: Authors: Lubet RA, Beger RD, Miller MS, Luster J, Seifried HE, Grubbs CJ Abstract To determine the effects of diet, rats were placed on a standard diet (4% fat) or on a modified Western (high-fat diet, HFD) diet (21% fat) at 43 days of age (DOA) and administered methylnitrosourea (MNU) at 50 DOA. Rats were administered effective (tamoxifen, vorozole, and Targretin) or ineffective (metformin and Lipitor) chemopreventive agents either by daily gavage or in the diet beginning at 57 DOA and continuing until sacrifice (190 DOA). Latency period of the tumors was determined by palpation, and multiplicity and cancer weights per rat were determined at final sacrifice. Rats on the HFD versus standard diet had: (i) a 6% increase in final body weights; (ii) significant decreases in tumor latency; and (iii) significant increases in final tumor multiplicity and average tumor weight. Tamoxifen, vorozole, and Targretin were highly effective preventive agents, whereas Lipitor and metformin were ineffective in rats on either diet. Serum was collected at 78 DOA and at sacrifice (190 DOA), and metabolomics were determined to identify the metabolite changes due to diets and effective agents. Rats given the HFD had increased levels of saturated free fatty acids (including myristate) and decreased levels of 2-aminooctanoate. Furthermore, rats on the HFD diet had increased levels of 2-aminobutyrate and decreases in glycine markers previously identified as indicators of prediabetes. Targretin increased long-chain glycophospholipids (e.g., oleyl-linoleoyl-glycerophosphocholine) and decreased primary bile acids (e.g., taurocholate). Tamoxifen increased palmitoyl-linoleoyl-glycophosphocholine and decreased stearoyl-arachidonyl glycophosphocholine. Finally, increased levels of methylated nucleotides (5-methylcytidine) and decreased levels of urea cycle metabolites (N-acetylcitrulline) were associated with the presence of mammary cancers. Cancer Prev Res; 11(12); 1-10. ©2018 AACR. PMID: 30459210 [PubMed - as supplied by publisher]

Related Articles Ultraviolet (IUV) and mass spectrometry (IMS) imaging for the deconvolution of microbial interactions. BMC Syst Biol. 2018 Nov 20;12(Suppl 5):99 Authors: González-Menéndez V, Martínez G, Serrano R, Muñoz F, Martín J, Genilloud O, Tormo JR Abstract BACKGROUND: Spatial localization of natural products or proteins during microbial interactions can help to identify new antimicrobials both as offensive or defensive agents. Visible spatial interactions have been used for decades to enhance Drug Discovery processes both in industry and academia. RESULTS: Herein we describe an automated micro-extraction methodology, that coupled with the previously described HPLC-Studio 2.0 software and the new development, the MASS-Studio 1.0 software, can combine multiple chemical analyses to generate ultraviolet (UV) and mass spectrometry (MS) images from traditional affordable analytical equipment. As a proof of concept, we applied this methodology on two microbial antagonisms observed among co-habitant endophytes isolated from endemic plants of arid areas of the south of Europe. CONCLUSIONS: The use of UV and MS images highlighted interacting naturals products and allowed clear identification of induced molecules of interest not produced by the strains when cultured individually. PMID: 30458793 [PubMed - in process]