PubMed

Related Articles Exhaled breath analysis: a review of 'breath-taking' methods for off-line analysis. Metabolomics. 2017;13(10):110 Authors: Lawal O, Ahmed WM, Nijsen TME, Goodacre R, Fowler SJ Abstract BACKGROUND: The potential of exhaled breath sampling and analysis has long attracted interest in the areas of medical diagnosis and disease monitoring. This interest is attributed to its non-invasive nature, access to an unlimited sample supply (i.e., breath), and the potential to facilitate a rapid at patient diagnosis. However, progress from laboratory setting to routine clinical practice has been slow. Different methodologies of breath sampling, and the consequent difficulty in comparing and combining data, are considered to be a major contributor to this. To fulfil the potential of breath analysis within clinical and pre-clinical medicine, standardisation of some approaches to breath sampling and analysis will be beneficial. OBJECTIVES: The aim of this review is to investigate the heterogeneity of breath sampling methods by performing an in depth bibliometric search to identify the current state of art in the area. In addition, the review will discuss and critique various breath sampling methods for off-line breath analysis. METHODS: Literature search was carried out in databases MEDLINE, BIOSIS, EMBASE, INSPEC, COMPENDEX, PQSCITECH, and SCISEARCH using the STN platform which delivers peer-reviewed articles. Keywords searched for include breath, sampling, collection, pre-concentration, volatile. Forward and reverse search was then performed on initially included articles. The breath collection methodologies of all included articles was subsequently reviewed. RESULTS: Sampling methods differs between research groups, for example regarding the portion of breath being targeted. Definition of late expiratory breath varies between studies. CONCLUSIONS: Breath analysis is an interdisciplinary field of study using clinical, analytical chemistry, data processing, and metabolomics expertise. A move towards standardisation in breath sampling is currently being promoted within the breath research community with a view to harmonising analysis and thereby increasing robustness and inter-laboratory comparisons. PMID: 28867989 [PubMed]

Related Articles Identification of weak and gender specific effects in a short 3 weeks intervention study using barley and oat mixed linkage β-glucan dietary supplements: a human fecal metabolome study by GC-MS. Metabolomics. 2017;13(10):108 Authors: Trimigno A, Khakimov B, Mejia JLC, Mikkelsen MS, Kristensen M, Jespersen BM, Engelsen SB Abstract INTRODUCTION: Mixed-linkage (1→3),(1→4)-β-d-glucans (BG) reduce cholesterol level and insulin response in humans. Despite this, their role in human metabolism and a mode of action remains largely unknown. OBJECTIVES: To investigate the effects of three structurally different BG on human fecal metabolome in a full cross-over intervention using GC-MS metabolomics. METHODS: Over three weeks of intervention, young healthy adults received food supplemented with BG from oat, two different BG from barley or a non-fiber control in a full cross-over design. Untargeted metabolomics and short chain fatty acid analysis was performed on day three fecal samples. ANOVA-simultaneous component analysis was applied to partition the data variation according to the study design, and PLS-DA was used to select most discriminative metabolite markers. RESULTS: Univariate and multivariate data analysis revealed a dominating effect of inter-individual variances followed by a gender effect. Weak effects of BG intake were identified including an increased level of gamma-amino-butyrate and palmitoleic acid in males and a decreased level of enterolactone in females. Barley and oat derived BG were found to influence the human fecal metabolome differently. Barley BG increased the relative level of formate in males and isobutyrate, isovalerate, 2-methylbutyrate in females. In total 15, 3 and 11 human fecal metabolites were significantly different between control vs. BG, control vs. oat BG, and barley BG vs. oat BG, respectively. CONCLUSIONS: The study show that human fecal metabolome largely reflects individual (∼28% variation) and gender (∼15% variation) differences, whereas the treatment effect of the BG (∼8% variation) only manifests in a few key metabolites (primarily by the metabolites: d-2-aminobutyric acid, palmitoleic acid, linoleic acid and 11-eicosenoic acid). PMID: 28867988 [PubMed]

Related Articles A Metabolic Study on the Biochemical Effects of Chiral Illegal Drugs in Rats Using (1)H-NMR Spectroscopy. Yakugaku Zasshi. 2017;137(9):1147-1154 Authors: Fukuhara K, Ohno A, Kikura-Hanajiri R Abstract  Considering the pharmacological effects of chiral drugs, enantiopure drugs may differ from their racemic mixture formulation in efficacy, potency, or adverse effects. Levomethorphan (LVM) and Dextromethorphan (DXM) act on the central nervous system and exhibit different pharmacological features. LVM, the l-stereoisomer of methorphan, shows many similarities to opiates such as heroin, morphine and codeine, including the potential for addiction, while the d-stereoisomer, DXM, does not have the same opioid effect. In the present study, NMR-based metabolomics were performed on the urine of rats treated with these stereoisomers, and showed significant differences in metabolic profiles. In urine within 24 h after treatment of these samples, levels of citrate, 2-oxoglutarate, creatine, and dimethylglycine were higher in LVM-treated rats than in DXM-treated rats. While urinary levels of hippurate and creatinine gradually increased over 72 h in DXM-treated rats, these metabolites were decreased in the urine by 48-72 h after treatment with LVM. The levels of these changed metabolites may provide the first evidence for different cellular responses to the metabolism of stereoisomers. PMID: 28867701 [PubMed - in process]

Related Articles Ascaroside Profiling of Caenorhabditis elegans using GC-EIMS. Anal Chem. 2017 Sep 03;: Authors: von Reuss SH, Dolke F, Dong C Abstract Nematodes such as the model organism Caenorhabditis elegans produce homologous series of L-ascarylose-derived glyco-lipids called ascarosides, which include several highly potent signals in intra and interspecies communication as well as cross-kingdom interactions. Given their low concentrations and large number of structurally similar components, mass spectrometric screens based on HPLC-ESI-MS/MS are commonly employed for ascaroside detection and quantification. Here, we describe a complementary GC-EIMS screen that utilizes an ascarylose-derived K1-fragment ion signal at m/z 130.1 [C6H14OSi](+●) to highlight known as well as yet unidentified ascaroside components in TMS-derivatized crude nematode exo-metabolome extracts. GC-EIMS-based ascaroside profiling of wild-type and mutant C. elegans facilitates the analysis of all basic ascarosides using the same ionization technique while providing excellent resolution for the complete homologous series with sidechains ranging from 3 to 33 carbons. Combined screening for m/z 130.1 along with sidechain-specific J1 [M-173] and J2 [M-291] fragment ions, as well as additional characteristic marker ions from α-cleavage, enables convenient structure assignment of ca. 200 components from wild-type and peroxisomal β-oxidation mutants including (ω-1)-linked acyl, enoyl, β-hydroxyacyl and 2-ketoalkyl ascarosides along with their (ω)-linked or α-methyl isomers and ethanolamide derivatives, as well as 2-hydroxyalkyl ascarosides. Given the widespread availability of GC-MS and its increasing popularity in metabolomics this method will promote the identification of ascarosides in C. elegans and other nematodes. PMID: 28866881 [PubMed - as supplied by publisher]

Related Articles Oxidative environment causes molecular remodeling in embryonic heart-a metabolomic and lipidomic fingerprinting analysis. Environ Sci Pollut Res Int. 2017 Sep 02;: Authors: Manickaraj S, Thirumalai D, Manjunath P, Sekarbabu V, Jeganathan S, Sundaresan L, Subramaniyam R, Jeganathan M Abstract Environmental factors including pollution affect human health, and the unifying factor in determining toxicity and pathogenesis for a wide array of environmental factors is oxidative stress. Here, we created the oxidative environment with 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH) and consequent cardiac remodeling in chick embryos. The metabolite fingerprint of heart tissue was obtained from Fourier transform infrared (FTIR) spectroscopic analysis. The global lipidomic analysis was done using electrospray ionization coupled with tandem mass spectrometry (ESI-MS/MS) by precursor ion scanning and neutral loss scanning methods. Further, the fatty acid levels were quantified in AAPH-treated H9c2 cardiomyoblasts with gas chromatography-mass spectrometry (GC-MS). Lipidomic fingerprinting study indicated that majority of differentially expressed phospholipids species in heart tissue belonged to ether phosphatidylcholine (ePC) species, and we conclude that excess oxidative environment may alter the phospholipid metabolism at earlier stages of cardiac remodeling. PMID: 28866837 [PubMed - as supplied by publisher]

Related Articles Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer. Redox Biol. 2017 Aug 10;14:47-58 Authors: Andrisic L, Dudzik D, Barbas C, Milkovic L, Grune T, Zarkovic N Abstract Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine. PMID: 28866248 [PubMed - as supplied by publisher]

Related Articles Mapping the Arabidopsis metabolic landscape by untargeted metabolomics at different environmental conditions. Mol Plant. 2017 Aug 30;: Authors: Wu S, Tohge T, Cuadros-Inostroza Á, Tong H, Tenenboim H, Kooke R, Méret M, Keurentjes JB, Nikoloski Z, Fernie AR, Willmitzer L, Brotman Y Abstract Metabolic genome-wide association studies (mGWAS), whereupon metabolite levels are regarded as traits, can help unravel the genetic basis of metabolic networks. 309 Arabidopsis accessions were grown under two independent environmental conditions (control and stress) and subjected to untargeted LC-MS-based metabolomics; levels of the obtained hydrophilic metabolites were used in GWAS. Our two-condition-based GWAS for more than 3,000 semi-polar metabolites resulted in the detection of 123 highly resolved metabolite quantitative trait loci (mQTL) (p ≤ 1.0E-08), 24.39% of which were environment-specific. Interestingly, differently from natural variation in Arabidopsis primary metabolites, which tends to be controlled by a large number of small-effect loci, here we found several major large-effect loci alongside a vast number of small-effect loci controlling variation of secondary metabolites. The two-condition-based GWAS was followed by integration with network-derived metabolite-transcript correlations using a time-course stress experiment. With this integrative approach, we selected 70 key candidate associations between structural genes and metabolites, and experimentally validated eight of the novel associations, two of them showing differential genetic regulation in the two environments studied. We demonstrate the power of combining large-scale untargeted metabolomics-based GWAS with time-course-derived networks both performed under different abiotic environments for identifying metabolite-gene associations, providing novel global insights into the metabolic landscape of Arabidopsis. PMID: 28866081 [PubMed - as supplied by publisher]

Related Articles Investigation of the preventive effect of sijunzi decoction on mitomycin C-induced immunotoxicity in rats by (1)H-NMR and MS-based untargeted metabolomic analysis. J Ethnopharmacol. 2017 Aug 30;: Authors: Guan Z, Wu J, Wang C, Zhang F, Wang Y, Wang M, Zhao M, Zhao C Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer. AIM OF THE STUDY: The aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action. MATERIALS AND METHODS: NMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways. RESULTS: 8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism. CONCLUSIONS: The variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism. PMID: 28866044 [PubMed - as supplied by publisher]

Related Articles Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study. Hum Genomics. 2017 Sep 02;11(1):21 Authors: Ohnishi J, Ayuzawa S, Nakamura S, Sakamoto S, Hori M, Sasaoka T, Takimoto-Ohnishi E, Tanatsugu M, Murakami K Abstract BACKGROUND: Growing evidence suggests that spiritual/religious involvement may have beneficial effects on both psychological and physical functions. However, the biological basis for this relationship remains unclear. This study explored the role of spiritual/religious involvement across a wide range of biological markers, including transcripts and metabolites, associated with the psychological aspects of empathy in Buddhist priests. METHODS: Ten professional Buddhist priests and 10 age-matched non-priest controls were recruited. The participants provided peripheral blood samples for the analysis of gene expression and metabolic profiles. The participants also completed validated questionnaires measuring empathy, the Health-Promoting Lifestyle Profile-II (HPLP-II), and a brief-type self-administered diet history questionnaire (BDHQ). RESULTS: The microarray analyses revealed that the distinct transcripts in the Buddhist priests included up-regulated genes related to type I interferon (IFN) innate anti-viral responses (i.e., MX1, RSAD2, IFIT1, IFIT3, IFI27, IFI44L, and HERC5), and the genes C17orf97 (ligand of arginyltranseferase 1; ATE1), hemoglobin γA (HBG1), keratin-associated protein (KRTAP10-12), and sialic acid Ig-like lectin 14 (SIGLEC14) were down-regulated at baseline. The metabolomics analysis revealed that the metabolites, including 3-aminoisobutylic acid (BAIBA), choline, several essential amino acids (e.g., methionine, phenylalanine), and amino acid derivatives (e.g., 2-aminoadipic acid, asymmetric dimethyl-arginine (ADMA), symmetric dimethyl-arginine (SMDA)), were elevated in the Buddhist priests. By contrast, there was no significant difference of healthy lifestyle behaviors and daily nutrient intakes between the priests and the controls in this study. With regard to the psychological aspects, the Buddhist priests showed significantly higher empathy compared with the control. Spearman's rank correlation analysis showed that empathy aspects in the priests were significantly correlated with the certain transcripts and metabolites. CONCLUSIONS: We performed in vivo phenotyping using transcriptomics, metabolomics, and psychological analyses and found an association between empathy and the phenotype of Buddhist priests in this pilot study. The up-regulation of the anti-viral type I IFN responsive genes and distinct metabolites in the plasma may represent systemic biological adaptations with a unique signature underlying spiritual/religious practices for Buddhists. PMID: 28865488 [PubMed - in process]

Impact of inoculum sources on biotransformation of pharmaceuticals and personal care products. Water Res. 2017 Aug 21;125:227-236 Authors: Kim S, Rossmassler K, Broeckling CD, Galloway S, Prenni J, De Long SK Abstract Limited knowledge of optimal microbial community composition for PPCP biotreatment, and of the microbial phylotypes that drive biotransformation within mixed microbial communities, has hindered the rational design and operation of effective and reliable biological PPCP treatment technologies. Herein, bacterial community composition was investigated as an isolated variable within batch biofilm reactors via comparison of PPCP removals for three distinct inocula. Inocula pre-acclimated to model PPCPs were derived from activated sludge (AS), ditch sediment historically-impacted by wastewater treatment plant effluent (Sd), and material from laboratory-scale soil aquifer treatment (SAT) columns. PPCP removals were found to be substantially higher for AS- and Sd-derived inocula compared to the SAT-derived inocula despite comparable biomass. Removal patterns differed among the 6 model compounds examined (diclofenac, 5-fluorouracil, gabapentin, gemfibrozil, ibuprofen, and triclosan) indicating differences in biotransformation mechanisms. Sphingomonas, Beijerinckia, Methylophilus, and unknown Cytophagaceae were linked with successful PPCP biodegradation via next-generation sequencing of 16S rRNA genes over time. Results indicate the criticality of applying engineering approaches to control bacterial community compositions in biotreatment systems. PMID: 28865372 [PubMed - as supplied by publisher]

Metabolomic study for monitoring of biomarkers in mouse plasma with asthma by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Aug 30;1063:156-162 Authors: Seo C, Hwang YH, Lee HS, Kim Y, Shin TH, Lee G, Son YJ, Kim H, Yee ST, Park AK, Paik MJ Abstract Asthma is a multifaceted chronic disease caused by an alteration of various genetic and environmental factors that is increasing in incidence worldwide. However, the biochemical mechanisms regarding asthma are not completely understood. Thus, we performed of metabolomic study for understanding of the biochemical events by monitoring of altered metabolism and biomarkers in asthma. In mice plasma, 27 amino acids(AAs), 24 fatty acids(FAs) and 17 organic acids(OAs) were determined by ethoxycarbonyl(EOC)/methoxime(MO)/tert-butyldimethylsilyl(TBDMS) derivatives with GC-MS. Their percentage composition normalized to the corresponding mean levels of control group. They then plotted as star symbol patterns for visual monitoring of altered metabolism, which were characteristic and readily distinguishable in control and asthma groups. The Mann-Whitney test revealed 25 metabolites, including eight AAs, nine FAs and eight OAs, which were significantly different (p<0.05), and orthogonal partial least-squares-discriminant analysis revealed a clear separation of the two groups. In classification analysis, palmitic acid and methionine were the main metabolites for discrimination between asthma and the control followed by pipecolic, lactic, α-ketoglutaric, and linoleic acids for high classification accuracy as potential biomarkers. These explain the metabolic disturbance in asthma for AAs and FAs including intermediate OAs related to the energy metabolism in the TCA cycle. PMID: 28865332 [PubMed - as supplied by publisher]

Related Articles Proteomics and (1)H NMR-based metabolomics analysis of pathogenic Vibrio vulnificus aquacultures isolated from sewage drains. Environ Sci Pollut Res Int. 2017 Sep 01;: Authors: Zhang C, Wang Z, Zhang D, Zhou J, Lu C, Su X, Ding D Abstract Vibrio bacteria live in both marine and freshwater habitats and are associated with aquatic animals. Vibrio vulnificus is a pathogenic bacterium that infects people and livestock. It is usually found in offshore waters or within fish and shellfish. This study presents a comparative proteomic analysis of the outer membrane protein (OMP) changes in V. vulnificus proteins after stimulation with sewage from sewage drains. Using two-dimensional electrophoresis followed by MALDI-TOF MS/MS, 32 protein spots with significant differences in abundance were identified and characterized. These identified proteins were found to be involved in various functional categories, including catalysis, transport, membrane proteins progresses, receptor activity, energy metabolism, cytokine activity, and protein metabolism. The mRNA expression levels of 12 differential proteins were further assessed by qRT-PCR. Seven genes including carboxypeptidase, hemoglobin receptor, succinate dehydrogenase iron-sulfur subunit, ATP synthase subunit alpha, thioredoxin, succinyl-CoA synthetase subunit, and alanine dehydrogenase were downregulated upon stimulation, whereas the protein expression levels HupA receptor, type I secretion outer membrane protein, glutamine synthetase, superoxide dismutase, OmpU, and VuuA were upregulated. (1)H NMR spectra showed 18 dysregulated metabolites from V. vulnificus after the sewage stimulation and the pathogenicity was enhanced after that. PMID: 28864971 [PubMed - as supplied by publisher]

Related Articles Novel Interactions between Gut Microbiome and Host Drug-processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals PBDEs. Drug Metab Dispos. 2017 Sep 01;: Authors: Li CY, Lee S, Cade S, Kuo LJ, Schultz IR, Bhatt DK, Prasad B, Bammler TK, Cui JY Abstract The gut microbiome is a novel frontier in xenobiotic metabolism. Polybrominated diphenyl ethers (PBDEs), especially BDE-47 and BDE-99, are among the most abundant and persistent environmental contaminants that produce a variety of toxicities. Little is known about how the gut microbiome affects the hepatic metabolism of PBDEs and the PBDE-mediated regulation of drug-processing genes (DPGs) in vivo. The goal of this study was to determine the role of gut microbiome in modulating the hepatic biotransformation of PBDEs. Nine-week-old male C57BL/6J conventional (CV) or germ free (GF) mice were treated with vehicle, BDE-47 or BDE-99 (100 mol/kg) for four days. Following BDE-47 treatment, GF mice had higher level of 5-OH-BDE-47 but lower levels of 4 other metabolites in liver than CV mice; whereas following BDE-99 treatment, GF mice had lower levels of 4 minor metabolites in liver than CV mice. RNA-Seq demonstrated that the hepatic expression of DPGs was regulated by both PBDEs and enterotypes. Under basal condition, the lack of gut microbiome up-regulated the Cyp2c subfamily but down-regulated the Cyp3a subfamily. Following PBDE exposure, certain DPGs were differentially regulated by PBDEs in a gut microbiome-dependent manner. Interestingly, the lack of gut microbiome augmented PBDE-mediated up-regulation of many DPGs, such as Cyp1a2 and Cyp3a11 in mouse liver, which was further confirmed by targeted metabolomics. The lack of gut microbiome also augmented the Cyp3a enzyme activity in liver. In conclusion, our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs. PMID: 28864748 [PubMed - as supplied by publisher]

Related Articles Metabolomics in Yeast. Cold Spring Harb Protoc. 2017 Sep 01;2017(9):pdb.top083576 Authors: Caudy AA, Mülleder M, Ralser M Abstract Budding yeast has from the beginning been a major eukaryotic model for the study of metabolic network structure and function. This is attributable to both its genetic and biochemical capacities and its role as a workhorse in food production and biotechnology. New inventions in analytical technologies allow accurate, simultaneous detection and quantification of metabolites, and a series of recent findings have placed the metabolic network at center stage in the physiology of the cell. For example, metabolism might have facilitated the origin of life, and in modern organisms it not only provides nutrients to the cell but also serves as a buffer to changes in the cellular environment, a regulator of cellular processes, and a requirement for cell growth. These findings have triggered a rapid and massive renaissance in this important field. Here, we provide an introduction to analysis of metabolomics in yeast. PMID: 28864573 [PubMed - in process]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/09/02PubMed 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.

Clinical Metabolomics and Glaucoma. Ophthalmic Res. 2017 Sep 01;: Authors: Barbosa-Breda J, Himmelreich U, Ghesquière B, Rocha-Sousa A, Stalmans I Abstract Glaucoma is one of the leading causes of irreversible blindness worldwide. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression. Metabolomics is the study of all metabolites in an organism, and it has the potential to provide a biomarker. This review summarizes the findings of metabolomics in glaucoma patients and explains why this field is promising for new research. We identified published studies that focused on metabolomics and ophthalmology. After providing an overview of metabolomics in ophthalmology, we focused on human glaucoma studies. Five studies have been conducted in glaucoma patients and all compared patients to healthy controls. Using mass spectrometry, significant differences were found in blood plasma in the metabolic pathways that involve palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors. For nuclear magnetic resonance spectroscopy, a high glutamine-glutamate/creatine ratio was found in the vitreous and lateral geniculate body; no differences were detected in the optic radiations, and a lower N-acetylaspartate/choline ratio was observed in the geniculocalcarine and striate areas. Metabolomics can move glaucoma care towards a personalized approach and provide new knowledge concerning the pathophysiology of glaucoma, which can lead to new therapeutic options. PMID: 28858875 [PubMed - as supplied by publisher]

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol. Molecules. 2017 Aug 31;22(9): Authors: Zou L, Zhang Y, Li W, Zhang J, Wang D, Fu J, Wang P Abstract Natural borneol (NB, called "Bingpian") is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for NB in clinics. However, little is known about the effects of SB instead of NB. Herein, the aim of the present study was to compare NB and SB on chemical profiles by gas chromatography-mass spectrometer (GC-MS) analysis, anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomic approaches in endotoxic fever induced in rats. Results showed that, in total, 13 volatile components could be identified in NB and SB by GC-MS analysis, in which a significant difference between them still existed. The main constituents in SB were iso-borneol and borneol, while borneol contributes to 98.96% of the amount in NB. Additionally, both NB and SB exhibited remarkable anti-inflammatory effects to reduce the level of inflammatory factors including NO, TNF-α and IL-6 in LPS-induced RAW 264.7 macrophages, and lower the high body temperature in rats with endotoxic fever induced by LPS. Moreover, it seems that NB exhibited higher efficacy than SB. The unequal bioactive efficiency between NB and SB was also indicated by means of non-targeting metabolomics. Based on UPLC-Q-TOF/MS technology, 12 biomarkers in the serum of fever rats were identified. Pathway analysis revealed that the anti-fever effect of NB and SB was related to regulating the abnormal glycerophospholipid, linoleic acid and alpha-linoleic acid metabolism pathways in the fever model. Results indicated that there was still a great difference between NB and SB involving chemical constituents, anti-inflammation activity and the ability to regulate the abnormal metabolism pathways of the fever model. Certainly, further studies are warranted to better understand the replacement rationale in medicinal application. PMID: 28858264 [PubMed - in process]

12-OH-17,18-epoxyeicosatetraenoic acid alleviates eosinophilic airway inflammation in murine lungs. Allergy. 2017 Aug 30;: Authors: Mochimaru T, Fukunaga K, Miyata J, Matsusaka M, Masaki K, Kabata H, Ueda S, Suzuki Y, Goto T, Urabe D, Inoue M, Isobe Y, Arita M, Betsuyaku T Abstract BACKGROUND: Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega-6 fatty acid, is metabolized into cysteinyl leukotriene with pro-inflammatory properties for allergic inflammation, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti-inflammatory effects. In this study, we investigated the mechanism underlying the counter-regulatory roles of EPA in inflamed lungs. METHODS: Male C57BL6 mice were sensitized and challenged by OVA. After EPA treatment, we evaluated the cell count of BALF, mRNA expressions in the lungs by q-PCR, and the amounts of lipid mediators by Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics. We investigated the effect of the metabolite of EPA in vivo and vitro study. RESULTS: EPA treatment reduced accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA-derived metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12-OH-17,18-EpETE attenuated airway eosinophilic inflammation through downregulation of C-C chemokine motif 11 (CCL11) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin-4. CONCLUSION: These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12-OH-17,18-EpETE is a potential therapeutic target for the management of asthma. This article is protected by copyright. All rights reserved. PMID: 28857178 [PubMed - as supplied by publisher]

Mass-spectrometric detection of omega-oxidation products of aliphatic fatty acids in exhaled breath. Anal Chem. 2017 Aug 31;: Authors: Gaugg MT, Bruderer T, Nowak N, Eiffert L, Sinues PM, Kohler M, Zenobi R Abstract Omega-oxidation is a fatty acid degradation pathway that can occur alternatively to the dominant β oxidation. The dysregulation of fatty acid oxidation has been related with a variety of diseases, termed fatty acid oxidation disorders. This work shows evidence for real-time detection in exhaled breath of the complete series of saturated linear ω hydroxyalkanoic acids, ω-oxoalkanoic acids and alkanedioic acids with carbon chain lengths of 5 15. We present a comprehensive analytical workflow using on-line and subsequent off-line methods: secondary electrospray ionization mass spectrometry of exhaled breath and UHPLC-HRMS/MS experiments using exhaled breath condensate, respectively. By analyzing on-line breath measurements of 146 healthy individuals, we were able to obtain strong evidence for the correlation of these metabolite families. This enabled us to monitor the full ω-oxidation pathway in human exhaled breath. We could unambiguously identify these compounds, many of which have never been reported in breath so far. This comprehensive study on breath metabolites reinforces the notion of breath as a valuable source of information, which is underexploited in metabolomics. PMID: 28856884 [PubMed - as supplied by publisher]

Bortezomib resistance in multiple myeloma is associated with increased serine synthesis. Cancer Metab. 2017;5:7 Authors: Zaal EA, Wu W, Jansen G, Zweegman S, Cloos J, Berkers CR Abstract BACKGROUND: The proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy is restricted by the wide-spread occurrence of resistance. Metabolic alterations play an important role in cancer development and aid in the cellular adaptation to pharmacologically changed environments. Metabolic changes could therefore play an essential role in the development of drug resistance. However, specific metabolic pathways that can be targeted to improve bortezomib therapy remain unidentified. METHODS: We elucidated the metabolic mechanisms underlying bortezomib resistance by using mass spectrometry-based metabolomics and proteomics on BTZ-sensitive and BTZ-resistant multiple myeloma cell lines as well as in a set of CD138+ cells obtained from multiple myeloma patients. RESULTS: Our findings demonstrate that a rewired glucose metabolism sustains bortezomib resistance. Mechanistically, this results in higher activity of both the pentose phosphate pathway and serine synthesis pathway, ultimately leading to an increased anti-oxidant capacity of BTZ-resistant cells. Moreover, our results link both serine synthesis pathway activity and expression of 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of serine synthesis, to bortezomib resistance across different BTZ-resistant multiple myeloma cell lines. Consistently, serine starvation enhanced the cytotoxicity of bortezomib, underscoring the importance of serine metabolism in the response to BTZ. Importantly, in CD138+ cells of clinically bortezomib refractory multiple myeloma patients, PHGDH expression was also markedly increased. CONCLUSIONS: Our findings indicate that interfering with serine metabolism may be a novel strategy to improve bortezomib therapy and identify PHGDH as a potential biomarker for BTZ resistance. PMID: 28855983 [PubMed]