PubMed

Related Articles Multivariate strategy for the sample selection and integration of multi-batch data in metabolomics. Metabolomics. 2017;13(10):114 Authors: Surowiec I, Johansson E, Torell F, Idborg H, Gunnarsson I, Svenungsson E, Jakobsson PJ, Trygg J Abstract INTRODUCTION: Availability of large cohorts of samples with related metadata provides scientists with extensive material for studies. At the same time, recent development of modern high-throughput 'omics' technologies, including metabolomics, has resulted in the potential for analysis of large sample sizes. Representative subset selection becomes critical for selection of samples from bigger cohorts and their division into analytical batches. This especially holds true when relative quantification of compound levels is used. OBJECTIVES: We present a multivariate strategy for representative sample selection and integration of results from multi-batch experiments in metabolomics. METHODS: Multivariate characterization was applied for design of experiment based sample selection and subsequent subdivision into four analytical batches which were analyzed on different days by metabolomics profiling using gas-chromatography time-of-flight mass spectrometry (GC-TOF-MS). For each batch OPLS-DA(®) was used and its p(corr) vectors were averaged to obtain combined metabolic profile. Jackknifed standard errors were used to calculate confidence intervals for each metabolite in the average p(corr) profile. RESULTS: A combined, representative metabolic profile describing differences between systemic lupus erythematosus (SLE) patients and controls was obtained and used for elucidation of metabolic pathways that could be disturbed in SLE. CONCLUSION: Design of experiment based representative sample selection ensured diversity and minimized bias that could be introduced at this step. Combined metabolic profile enabled unified analysis and interpretation. PMID: 28890672 [PubMed]

Related Articles Metabolic profiles revealed anti-ischemia-reperfusion injury of Yangxinshi tablet in Rats. J Ethnopharmacol. 2017 Sep 07;: Authors: Zhang H, Zhao Y, Xia Z, Du H, Gao Y, Xue D, Zhu Z, Chai Y Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial ischemia-reperfusion (I/R) injury is a serious injury that is resulted from the recovery of blood supply after myocardial ischemia. Yangxinshi tablet is a compound Chinese herbal preparation and often used to alleviate the myocardial ischemia in clinical, but its protective mechanism of anti-myocardial ischemia reperfusion injury remains unclear. The objective of this study was to evaluate the anti-I/R injury effect of Yangxinshi tablet on a myocardial I/R rat model and to identify serum biomarker metabolites associated with I/R based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomic method, and explore the metabolic mechanism of anti-I/R injury of Yangxinshi tablet. MATERIALS AND METHODS: Unsupervised principle component analysis highlighted significant differences in the metabolome of the myocardial I/R, healthy control and drug-treated rats. Partial least squares-discriminant analysis revealed 25 metabolites as the most potential biomarker metabolites discriminating the myocardial I/R rats and control rats. Most of the metabolites were primarily involved in oxidative stress, energy metabolism, fatty acid metabolism, amino acid metabolism. These metabolites were validated by assessing the efficacy after intragastric administration of Yangxinshit ablet to the myocardial I/R rat model. RESULTS: Based on metabolomic results, the action mechanism of anti-I/R injury of Yangxinshi tablet was concluded as follows: (1) enhance the ability of scavenging free radicals and reactive oxygen species in vivo; (2) provide energy for myocardium via accelerating the intracellular carnitine transportion to accelerate the oxidation of fatty acid and (3) attenuate ceramide to reduce cardiomyocyte apoptosis. CONCLUSIONS: Yangxinshi tablet has cardio-protection effects on I/R rats via regulation of multiple metabolic pathways involving in oxidative stress, energy metabolism, fatty acid, and amino acid metabolisms. This study will be meaningful for its clinical application and valuable for further exploring the action mechanism of Yangxinshi tablet. PMID: 28889959 [PubMed - as supplied by publisher]

Related Articles α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017 Sep;18(9):985-994 Authors: Liu PS, Wang H, Li X, Chao T, Teav T, Christen S, Di Conza G, Cheng WC, Chou CH, Vavakova M, Muret C, Debackere K, Mazzone M, Huang HD, Fendt SM, Ivanisevic J, Ho PC Abstract Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, αKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming. PMID: 28714978 [PubMed - indexed for MEDLINE]

Related Articles Bioavailability of Microencapsulated Iron from Fortified Bread Assessed Using Piglet Model. Nutrients. 2017 Mar 13;9(3): Authors: Bryszewska MA, Laghi L, Zannoni A, Gianotti A, Barone F, Taneyo Saa DL, Bacci ML, Ventrella D, Forni M Abstract The aim of this study was to investigate the influence of oral iron supplementation, in the form of fortified breads, on the growth performance, health, iron status parameters, and fecal metabolome of anemic piglets. A study was conducted on 24 hybrid (Large White × Landrace × Duroc) piglets. From day 44, the post-natal 12 piglets were supplemented with 100 g of one of two experimental breads, each fortified with 21 mg of ferrous sulphate, either encapsulated or not. After one week of oral supplementation, hematological parameters (hematocrit value, hemoglobin, and red blood cells) showed statistically significant differences (p ≤ 0.05). Piglets fed with the fortified breads had higher iron concentrations in the heart, liver, and intestinal mucosa compared to anemic piglets fed with control bread. Gene expression of hepcidin, iron exporter ferroportin (IREG1), and divalent metal transporter 1 (DMT1), together with concentrations of plasma ferritin, showed no significant statistical differences between groups. Both fortified breads could be used as sources of bioavailable iron. The seven-day intervention trial showed microencapsulation to have only a mild effect on the effectiveness of iron supplementation in the form of fortified bread. PMID: 28335378 [PubMed - indexed for MEDLINE]

Related Articles Muscle Sympathetic Nerve Activity Is Associated With Elements of the Plasma Lipidomic Profile in Young Asian Adults. J Clin Endocrinol Metab. 2017 Jun 01;102(6):2059-2068 Authors: Eikelis N, Lambert EA, Phillips S, Sari CI, Mundra PA, Weir JM, Huynh K, Grima MT, Straznicky NE, Dixon JB, Schlaich MP, Meikle PJ, Lambert GW Abstract Background: Asian subjects are at increased cardio-metabolic risk at comparatively lower body mass index (BMI) compared with white subjects. Sympathetic nervous system activation and dyslipidemia, both characteristics of increased adiposity, appear to be related. We therefore analyzed the association of muscle sympathetic nerve activity (MSNA) with the plasma lipidomic profile in young adult Asian and white subjects. Methods: Blood samples were collected from 101 participants of either Asian or white background (age, 18 to 30 years; BMI, 28.1 ± 5.9 kg/m2). Lipids were extracted from plasma and analyzed using electrospray ionization-tandem mass spectrometry. MSNA was quantified using microneurography. The association of MSNA and obesity with lipid species was examined using linear regression analysis. Results: The plasma concentrations of total dihydroceramide, ceramide, GM3 ganglioside, lysoalkylphosphatidylcholine, alkenylphosphatidylethanolamine, and lysophosphatidylinositol were elevated in the Asian subjects relative to the white subjects. After adjustment for confounders, diacylglycerols and triacylglycerols, cholesterol esters, phosphatidylinositols, phosphatidylethanolamines, and phosphatidylglycerols bore significant associations with MSNA but only in the Asian subjects. These associations remained significant after further adjustment for the participants' degree of insulin resistance and appeared not to be related to differences in diet macronutrient content between groups. Conclusions: The lipidomic profile differs between Asian and white subjects. There exists a strong relationship between certain lipid species and MSNA. The association is stronger in Asian subjects, despite their lower BMI. This study demonstrates an association between circulating lipids and central sympathetic outflow. Whether the stronger association between the lipid profile and sympathetic activation underpins the apparent greater risk posed by increased adiposity in Asian individuals merits further attention. PMID: 28323975 [PubMed - indexed for MEDLINE]

Related Articles Randomized Controlled Trial of a MUFA or Fiber-Rich Diet on Hepatic Fat in Prediabetes. J Clin Endocrinol Metab. 2017 May 01;102(5):1765-1774 Authors: Errazuriz I, Dube S, Slama M, Visentin R, Nayar S, O'Connor H, Cobelli C, Das SK, Basu A, Kremers WK, Port J, Basu R Abstract Context: Increased prevalence of type 2 diabetes mellitus and prediabetes worldwide is attributed in part to an unhealthy diet. Objective: To evaluate whether 12 weeks of high monounsaturated fatty acid (MUFA) or fiber-rich weight-maintenance diet lowers hepatic fat and improves glucose tolerance in people with prediabetes. Design: Subjects underwent a [6, 6-2H2]-labeled 75-g oral glucose tolerance test to estimate hepatic insulin sensitivity and liver fat fraction (LFF) using magnetic resonance spectroscopy before and after intervention. Setting: Mayo Clinic Clinical Research Trials Unit. Participants: 43 subjects with prediabetes. Intervention: Subjects were randomized into three isocaloric weight-maintaining diets containing MUFA (olive oil), extra fiber, and standard US food (control-habitual diet). Outcome Measures: LFF, glucose tolerance, and indices of insulin action and secretion. Results: Body weight was maintained constant in all groups during the intervention. Glucose and hormonal concentrations were similar in all groups before, and unchanged after, 12 weeks of intervention. LFF was significantly lower after intervention in the MUFA group (P < 0.0003) but remained unchanged in the fiber (P = 0.25) and control groups (P = 0.45). After 12 weeks, LFF was significantly lower in the MUFA than in the control group (P = 0.01), but fiber and control groups did not differ (P = 0.41). Indices of insulin action and secretion were not significantly different between the MUFA and control groups after intervention (P ≥ 0.11), but within-group comparison showed higher hepatic (P = 0.01) and total insulin sensitivity (P < 0.04) with MUFA. Conclusions: Twelve weeks of a MUFA diet decreases hepatic fat and improves both hepatic and total insulin sensitivity. PMID: 28323952 [PubMed - indexed for MEDLINE]

Related Articles The Bactericidal Lectin RegIIIβ Prolongs Gut Colonization and Enteropathy in the Streptomycin Mouse Model for Salmonella Diarrhea. Cell Host Microbe. 2017 Feb 08;21(2):195-207 Authors: Miki T, Goto R, Fujimoto M, Okada N, Hardt WD Abstract The bactericidal lectin RegIIIβ is inducibly produced by intestinal epithelial cells as a defense against infection by enteropathogens. In the gut lumen, RegIIIβ kills not only certain enteropathogens, but also some commensal bacteria; thus, RegIIIβ is also thought to be an innate immune effector shaping microbiota composition and establishing intestinal homeostasis. Using the streptomycin mouse model for Salmonella colitis, we show that RegIIIβ can promote sustained gut colonization of Salmonella Typhimurium and prolong enteropathy. RegIIIβ expression was associated with suppression of Bacteroides spp. in the gut lumen, prolonged disease-associated alterations in colonic metabolism, and reduced luminal vitamin B6 levels. Supplementation with Bacteroides spp. or vitamin B6 accelerated pathogen clearance from the gut and remission of enteropathy. Our findings indicate that interventions at the level of RegIIIβ and supplementation with Bacteroides spp. or vitamin B6 might open new avenues for therapeutic intervention in the context of Salmonella colitis. PMID: 28111202 [PubMed - indexed for MEDLINE]

Related Articles A rabbit model for assessment of volatile metabolite changes observed from skin: a pressure ulcer case study. J Breath Res. 2017 Jan 09;11(1):016007 Authors: Schivo M, Aksenov AA, Pasamontes A, Cumeras R, Weisker S, Oberbauer AM, Davis CE Abstract Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes-some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath. PMID: 28068292 [PubMed - indexed for MEDLINE]

A Time for Metabolism and Hormones Book. 2016 Authors: Sassone-Corsi P, Christen Y Abstract A biological “circadian” clock governs nearly all aspects of mammalian behavior and physiology. This control extends from activities of entire organ systems down to individual cells, all of which contain autonomous molecular clocks. Under this control, a significant fraction of the cellular metabolome—the collection of all small-molecule metabolites—varies in abundance according to time of day. Comparing the rhythmic expression of transcripts, proteins, and metabolites has yielded valuable insights into clock-controlled physiological mechanisms. In the future, their analysis could provide a glimpse of instantaneous clock phase, even providing notions of clock time based upon molecules within a single breath. Such knowledge could be important for disease diagnosis and for chronopharmacology. PMID: 28892341

Identification and Quantification of Cyclic Di-Guanosine Monophosphate and Its Linear Metabolites by Reversed-Phase LC-MS/MS. Methods Mol Biol. 2017;1657:45-58 Authors: Bähre H, Kaever V Abstract Cyclic dinucleotides such as bis-(3',5')-cyclic dimeric guanosine monophosphate (3',3'-c-di-GMP) represent an important class of second messengers in bacteria and are involved in numerous (patho)physiological settings. Here, we describe a sensitive and specific quantification method for 3',3'-c-di-GMP by HPLC-coupled tandem mass spectrometry (LC-MS/MS). Additionally, linear 3',3'-c-di-GMP metabolites, i.e., 5'-phosphoguanylyl-3',5'-guanosine (pGpG) and 5'-guanosine monophosphate (5'-GMP), as well as cyclic guanosine monophosphate (3',5'-cGMP) and 3',3' c-di-GMP analogues (2',3'-c-di-GMP and 2',2'-c-di-GMP) can be simultaneously determined by this method. PMID: 28889285 [PubMed - in process]

geneSurv: An interactive web-based tool for survival analysis in genomics research. Comput Biol Med. 2017 Sep 05;89:487-496 Authors: Korkmaz S, Goksuluk D, Zararsiz G, Karahan S Abstract Survival analysis methods are often used in cancer studies. It has been shown that the combination of clinical data with genomics increases the predictive performance of survival analysis methods. But, this leads to a high-dimensional data problem. Fortunately, new methods have been developed in the last decade to overcome this problem. However, there is a strong need for easily accessible, user-friendly and interactive tool to perform survival analysis in the presence of genomics data. We developed an open-source and freely available web-based tool for survival analysis methods that can deal with high-dimensional data. This tool includes classical methods, such as Kaplan-Meier, Cox proportional hazards regression, and advanced methods, such as penalized Cox regression and Random Survival Forests. It also offers an optimal cutoff determination method based on maximizing several test statistics. The tool has a simple and interactive interface, and it can handle high dimensional data through feature selection and ensemble methods. To dichotomize gene expressions, geneSurv can identify optimal cutoff points. Users can upload their microarray, RNA-Seq, chip-Seq, proteomics, metabolomics or clinical data as a nxp dimensional data matrix, where n refers to samples and p refers to genes. This tool is available free at www.biosoft.hacettepe.edu.tr/geneSurv. All source code is available at https://github.com/selcukorkmaz/geneSurv under the GPL-3 license. PMID: 28889076 [PubMed - as supplied by publisher]

Imazalil exposure induces gut microbiota dysbiosis and hepatic metabolism disorder in zebrafish. Comp Biochem Physiol C Toxicol Pharmacol. 2017 Sep 06;: Authors: Jin C, Luo T, Zhu Z, Pan Z, Yang J, Wang W, Fu Z, Jin Y Abstract The fungicide imazalil (IMZ) is used extensively to preserve freshness, prevent decay and control fungal infections in fruits, vegetables or other plants. Recently, some studies have reported that the real in aquatic systems have reached very high levels. Here, male adult zebrafish were exposed to 100 and 1000μg/L IMZ for 1, 7, 21days, and the gut microbiota and hepatic metabolism were evaluated. Exposure to a high concentration of IMZ for 21days decreased mucin secretion in the gut. Sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant increase in the diversity of gut microbiota in male zebrafish. At the phylum level, the composition of Proteobacteria and Bacteroidetes was decreased, while those Fusobacteria and Firmicutes increased in the gut after exposure to 1000μg/L IMZ for 21days. At the genus level, 29 species of microorganisms were significantly changed after IMZ exposure. Based on GC/MS metabolomics analysis, 101 metabolites were observably significantly altered in the 1000μg/L IMZ-treatment group. These changed metabolites were mainly associated with the pathway of glycolysis, amino acid metabolism, and lipid metabolism. In addition, the transcription of some genes related to glycolysis and lipid metabolism, including Aco, Cpt1, Acc1, Srebp1a and Fas, was decreased significantly in the liver of zebrafish when exposed to 100 and 1000μg/L IMZ for 7 or 21days. These results indicated that exposure to IMZ could cause gut microbiota dysbiosis and metabolic disorders in adult zebrafish. PMID: 28888875 [PubMed - as supplied by publisher]

Impact of boiling on free and bound phenolic profile and antioxidant activity of commercial gluten-free pasta. Food Res Int. 2017 Oct;100(Pt 2):69-77 Authors: Rocchetti G, Lucini L, Chiodelli G, Giuberti G, Montesano D, Masoero F, Trevisan M Abstract Cooking by boiling dry pasta could have varying degrees of influence on nutritional and functional components. In the present study, its effect on total phenolic content and antioxidant capacity, as well as on the comprehensive profile of free and bound phenolics, was investigated in six commercial gluten-free (GF) pasta products. Overall, the heat treatment caused a significant reduction (P<0.01) of the total phenolic content as well as FRAP reducing power and ORAC radical scavenging, with significant differences among the pasta samples considered. The highest values were recorded in free phenolic fraction remaining in black rice (41mggallic acid equivalents100g(-1) and 25mmolTrolox Equivalents100g(-1)) and quinoa (24mggallic acid equivalents100g(-1) and 14mmolTrolox Equivalents100g(-1)) cooked GF pasta. Significant correlations (P<0.01) could be found between total phenolics and both the antioxidant capacity assays performed. UHPLC-ESI/QTOF-MS mass profiling allowed confirming the spectrophotometric results, while identifying the amount of free and bound fractions. Among phenolic classes, lignans exhibited the highest decrease during the cooking process, followed by stilbenes and flavonoids. However, phenolic acids and other phenolics showed the highest stability. Furthermore, cooking by boiling strongly lowered the bound-to-free ratio of phenolic compounds, by an averaged factor ranging from 14-folds for flavonoids to 5-folds for other classes of phenolics. PMID: 28888460 [PubMed - in process]

ANALYSIS OF EARTHWORM SUB-LETHAL TOXIC RESPONSES TO ATRAZINE EXPOSURE USING (1) H NUCLEAR MAGNETIC RESONANCE (NMR)-BASED METABOLOMICS. Environ Toxicol Chem. 2017 Sep 09;: Authors: Dani VD, Simpson AJ, Simpson MJ Abstract Atrazine toxicity to earthworms is still not fully understood, particularly at sub-lethal concentrations. Because of the ubiquity of atrazine in the environment, it is imperative to understand the impacts of atrazine presence on soil-dwelling organisms. To examine this in detail, we used (1) H nuclear magnetic resonance (NMR)-based metabolomics to elucidate earthworm (Eisenia fetida) responses after a 48 h of atrazine exposure in contact tests. Earthworms were exposed to four sub-lethal concentrations of 362.4 ng/cm(2) , 181.2 ng/cm(2) , 90.6 ng/cm(2) and 45.3 ng/cm(2) , which correspond to 1/8(th) , 1/16(th) , 1/32(nd) and 1/64(th) of the LC50 value respectively. After exposure, polar metabolites were isolated from earthworm tissues and analyzed using (1) H NMR spectroscopy. Sub-lethal atrazine exposure induced a non-monotonic response with respect to exposure concentration and caused an overall suppression in earthworm metabolism. Maltose, fumarate, malate, threonine/lactate, adenosine-5'-triphosphate (ATP), betaine, scyllo-inositol, glutamate, arginine and glutamine were the metabolites identified as most sensitive to atrazine exposure. These observed fluctuations in the metabolic profile suggest that atrazine reduced ATP synthesis and negatively impacted the health of earthworms with acute sub-lethal exposure. Our study also demonstrates the utility of NMR-based metabolomics for the basic assessment of sub-lethal toxicity which can then be used for more targeted approaches with other molecular techniques. This article is protected by copyright. All rights reserved. PMID: 28888035 [PubMed - as supplied by publisher]

Related Articles Metabolomics differences between silkworms (Bombyx mori) reared on fresh mulberry (Morus) leaves or artificial diets. Sci Rep. 2017 Sep 08;7(1):10972 Authors: Dong HL, Zhang SX, Tao H, Chen ZH, Li X, Qiu JF, Cui WZ, Sima YH, Cui WZ, Xu SQ Abstract Silkworms (Bombyx mori) reared on artificial diets have great potential applications in sericulture. However, the mechanisms underlying the enhancement of metabolic utilization by altering silkworm nutrition are unclear. The aim of this study was to investigate the mechanisms responsible for the poor development and low silk protein synthesis efficiency of silkworms fed artificial diets. After multi-generational selection of the ingestive behavior of silkworms to artificial diets, we obtained two strains, one of which developed well and another in which almost all its larvae starved to death on the artificial diets. Subsequently, we analyzed the metabolomics of larval hemolymph by gas chromatography/liquid chromatography-mass spectrometry, and the results showed that vitamins were in critically short supply, whereas the nitrogen metabolic end product of urea and uric acid were enriched substantially, in the hemolymph of the silkworms reared on the artificial diets. Meanwhile, amino acid metabolic disorders, as well as downregulation of carbohydrate metabolism, energy metabolism, and lipid metabolism, co-occurred. Furthermore, 10 male-dominant metabolites and 27 diet-related metabolites that differed between male and female silkworms were identified. These findings provide important insights into the regulation of silkworm metabolism and silk protein synthesis when silkworms adapt to an artificial diet. PMID: 28887546 [PubMed - in process]

Related Articles Dormant 5-lipoxygenase in inflammatory macrophages is triggered by exogenous arachidonic acid. Sci Rep. 2017 Sep 08;7(1):10981 Authors: Sorgi CA, Zarini S, Martin SA, Sanchez RL, Scandiuzzi RF, Gijón MA, Guijas C, Flamand N, Murphy RC, Faccioli LH Abstract The differentiation of resident tissue macrophages from embryonic precursors and that of inflammatory macrophages from bone marrow cells leads to macrophage heterogeneity. Further plasticity is displayed through their ability to be polarized as subtypes M1 and M2 in a cell culture microenvironment. However, the detailed regulation of eicosanoid production and its involvement in macrophage biology remains unclear. Using a lipidomics approach, we demonstrated that eicosanoid production profiles between bone marrow-derived (BMDM) and peritoneal macrophages differed drastically. In polarized BMDMs, M1 and M2 phenotypes were distinguished by thromboxane B2, prostaglandin (PG) E2, and PGD2 production, in addition to lysophospholipid acyltransferase activity. Although Alox5 expression and the presence of 5-lipoxygenase (5-LO) protein in BMDMs was observed, the absence of leukotrienes production reflected an impairment in 5-LO activity, which could be triggered by addition of exogenous arachidonic acid (AA). The BMDM 5-LO regulatory mechanism was not responsive to PGE2/cAMP pathway modulation; however, treatment to reduce glutathione peroxidase activity increased 5-LO metabolite production after AA stimulation. Understanding the relationship between the eicosanoids pathway and macrophage biology may offer novel strategies for macrophage-associated disease therapy. PMID: 28887514 [PubMed - in process]

Related Articles Sulfonolipids as novel metabolite markers of Alistipes and Odoribacter affected by high-fat diets. Sci Rep. 2017 Sep 08;7(1):11047 Authors: Walker A, Pfitzner B, Harir M, Schaubeck M, Calasan J, Heinzmann SS, Turaev D, Rattei T, Endesfelder D, Castell WZ, Haller D, Schmid M, Hartmann A, Schmitt-Kopplin P Abstract The gut microbiota generates a huge pool of unknown metabolites, and their identification and characterization is a key challenge in metabolomics. However, there are still gaps on the studies of gut microbiota and their chemical structures. In this investigation, an unusual class of bacterial sulfonolipids (SLs) is detected in mouse cecum, which was originally found in environmental microbes. We have performed a detailed molecular level characterization of this class of lipids by combining high-resolution mass spectrometry and liquid chromatography analysis. Eighteen SLs that differ in their capnoid and fatty acid chain compositions were identified. The SL called "sulfobacin B" was isolated, characterized, and was significantly increased in mice fed with high-fat diets. To reveal bacterial producers of SLs, metagenome analysis was acquired and only two bacterial genera, i.e., Alistipes and Odoribacter, were revealed to be responsible for their production. This knowledge enables explaining a part of the molecular complexity introduced by microbes to the mammalian gastrointestinal tract and can be used as chemotaxonomic evidence in gut microbiota. PMID: 28887494 [PubMed - in process]

Related Articles Approaches and techniques to characterize cancer metabolism in vitro and in vivo. Biochim Biophys Acta. 2017 Sep 05;: Authors: Zaimenko I, Lisec J, Stein U, Brenner W Abstract Cancer metabolism is wired to sustain uncontrollable cell proliferation and ensure cell survival. Given the multitude of available approaches to study metabolic alterations it remains a challenging task to select the most appropriate method. In this mini-review we describe how cancer metabolism can be studied in vitro and in vivo providing an overview of available approaches and techniques, discussing their advantages and drawbacks and guiding through selection of an appropriate method to address particular research needs. This work is particularly intended to those cancer researchers who are new in the field but want to investigate metabolic alterations in their cancer model systems. PMID: 28887205 [PubMed - as supplied by publisher]

From direct to indirect lithium targets: a comprehensive review of omics data. Metallomics. 2017 Sep 08;: Authors: Roux M, Dosseto A Abstract Metal ions are critical to a wide range of biological processes. Among them, lithium (Li) has been recognised for its benefit as a treatment for bipolar disorder (BD). However, we are yet to grasp the extent of its role in biological processes, despite its molecular targets having been extensively studied. Here we review a wide range of transcriptomic, proteomic and metabolomic studies in order to obtain a full picture of Li effects at various levels. Multifarious patterns of Li-regulated genes, proteins and metabolites are identified. Some of these patterns are explained as the outcomes of individual Li targets. For instance, Li inhibition of GSK-3 has a wide range of effects: axis development in embryos; cell and tissue differentiation, in particular neurogenesis and osteogenesis; or control of apoptosis. This results in neuroprotection and an attenuation of cognitive deficits. Lithium plays an important role in mitochondrial function, which it improves via its role in phospholipid metabolism and inositol depletion. This is also seen in metabolomics, where its role in the mitochondrial respiratory chain influences energy production and oxidative stress. Lithium also affects the proteins involved in the processing of APP, thus highlighting a possible involvement in Alzheimer's disease. Finally, Li also impacts lipid homeostasis, with studies showing that environmental exposure can impact lipid transport and prostaglandin synthesis. It is seldom possible to establish a causal relationship between Li targets at the molecular level and the resulting effects at the system level. For example, Li effects on adenylate cyclase regulation are not easily linked to any omic pattern despite the importance of the adenylate pathway. Nevertheless, refining our knowledge on the cellular functions of individual Li targets would improve our understanding and interpretation of omics data. This review demonstrates that Li is key to a wide range of processes at all levels, from neuroprotection to oxidative stress and energy production. A corollary of this work is the need for an increased awareness of environmental issues related to Li industrial wastes, in particular considering the widespread use of this metal in our modern society. PMID: 28885630 [PubMed - as supplied by publisher]

Dual RNA-Sequencing to Elucidate the Plant-Pathogen Duel. Curr Issues Mol Biol. 2017 Sep 08;27:127-142 Authors: Naidoo S, Visser EA, Zwart L, Toit YD, Bhadauria V, Shuey LS Abstract RNA-sequencing technology has been widely adopted to investigate host responses during infection with pathogens. Dual RNA-sequencing (RNA-seq) allows the simultaneous capture of pathogen specific transcripts during infection, providing a more complete view of the interaction. In this review, we focus on the design of dual RNA-seq experiments and the application of downstream data analysis to gain biological insight into both sides of the interaction. Recent literature in this area demonstrates the power of the dual RNA-seq approach and shows that it is not limited to model systems where genomic resources are available. A reduction in sequencing cost and single cell transcriptomics coupled with protein and metabolite level dual approaches are set to enhance our understanding of plant-pathogen interactions. Sequencing costs continue to decrease and single cell transcriptomics is becoming more feasible. In combination with proteomics and metabolomics studies, these technological advances are likely to contribute to our understanding of the temporal and spatial aspects of dynamic plant-pathogen interactions. PMID: 28885179 [PubMed - as supplied by publisher]