PubMed

Related Articles A proteometabolomic study of Actinidia deliciosa fruit development. J Proteomics. 2017 Nov 10;: Authors: Salzano AM, Sobolev A, Carbone V, Petriccione M, Renzone G, Capitani D, Vitale M, Minasi P, Pasquariello MS, Novi G, Zambrano N, Scortichini M, Mannina L, Scaloni A PMID: 29133123 [PubMed - as supplied by publisher]

Related Articles Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals. Elife. 2017 Nov 14;6: Authors: Kühl I, Miranda M, Atanassov I, Kuznetsova I, Hinze Y, Mourier A, Filipovska A, Larsson NG Abstract Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment. PMID: 29132502 [PubMed - as supplied by publisher]

Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation. Nat Chem Biol. 2017 Nov 13;: Authors: Beyer BA, Fang M, Sadrian B, Montenegro-Burke JR, Plaisted WC, Kok BPC, Saez E, Kondo T, Siuzdak G, Lairson LL Abstract Endogenous metabolites play essential roles in the regulation of cellular identity and activity. Here we have investigated the process of oligodendrocyte precursor cell (OPC) differentiation, a process that becomes limiting during progressive stages of demyelinating diseases, including multiple sclerosis, using mass-spectrometry-based metabolomics. Levels of taurine, an aminosulfonic acid possessing pleotropic biological activities and broad tissue distribution properties, were found to be significantly elevated (∼20-fold) during the course of oligodendrocyte differentiation and maturation. When added exogenously at physiologically relevant concentrations, taurine was found to dramatically enhance the processes of drug-induced in vitro OPC differentiation and maturation. Mechanism of action studies suggest that the oligodendrocyte-differentiation-enhancing activities of taurine are driven primarily by its ability to directly increase available serine pools, which serve as the initial building block required for the synthesis of the glycosphingolipid components of myelin that define the functional oligodendrocyte cell state. PMID: 29131145 [PubMed - as supplied by publisher]

Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders. Mass Spectrom Rev. 2017 Nov 12;: Authors: Luan H, Wang X, Cai Z Abstract Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the investigation of underlying mechanism of therapeutic strategies. PMID: 29130504 [PubMed - as supplied by publisher]

Combined Metabolomic and Correlation Networks Analyses Reveal Fumarase Insufficiency Altered Amino Acids Metabolism. Biomed Chromatogr. 2017 Nov 11;: Authors: Hou E, Li X, Liu Z, Zhang F, Tian Z Abstract Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased level of fumarate and decreased level of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles that induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient HUVEC cells and negative controls. A total of 24 altered metabolites involved in 7 metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, L-malic acid, L-aspartic acid, glycine and L-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. ALT and GDH activities increased significantly in fumarase deficiency HUVEC cells. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. PMID: 29130499 [PubMed - as supplied by publisher]

Related Articles Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway. Ocul Surf. 2017 Nov 09;: Authors: Charkoftaki G, Jester J, Thompson D, Vasiliou V Abstract PURPOSE: Nitrogen mustard (NM), which simulates the effects of sulfur mustard (SM), is a potent vesicant known to cause irreversible corneal damage. This study investigates the mechanisms by which NM induces corneal damage by examining the impact of NM exposure on the morphology and lipidome of the cornea. METHODS: Intact ex vivo rabbit eyes were placed in serum-free DMEM organ culture. NM (0, 1, 2.5, 5 or 10 mg/ml) was applied to the central cornea for 5, 10 or 15 min using a 5 mm filter disk and subsequently rinsed with DMEM. Corneas were then cultured for 3, 24, or 48 h before being fixed for morphological analysis or for 24 h before being snap- frozen for lipidomic analysis. RESULTS: No morphological changes were detected 3 h after NM exposure. Twenty-four h after exposure, 1 mg/ml NM caused erosion of the corneal epithelium, but no damage to the underlying stroma. Damage caused by 2.5 mg/ml NM extended almost two thirds through the corneal stroma, while 5 mg/ml completely penetrated the corneal stroma. Analtered lipid profile occurred 24 h after corneas were exposed to NM. Specific sphingomyelins, ceramides, and diacylglycerols were increased up to 9-, 60- and 10-fold, respectively. CONCLUSIONS: NM induces concentration- and exposure time-dependent damage to the cornea that increases in severity over time. Alterations in the sphingomyelin-ceramidepathway may contribute to the damaging effects of NM exposure. PMID: 29129753 [PubMed - as supplied by publisher]

Related Articles MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD(+) consumption. Nat Struct Mol Biol. 2017 Nov;24(11):902-910 Authors: Marjanović MP, Hurtado-Bagès S, Lassi M, Valero V, Malinverni R, Delage H, Navarro M, Corujo D, Guberovic I, Douet J, Gama-Perez P, Garcia-Roves PM, Ahel I, Ladurner AG, Yanes O, Bouvet P, Suelves M, Teperino R, Pospisilik JA, Buschbeck M Abstract Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD(+)-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD(+) consumption. The resultant accumulation of the NAD(+) precursor NMN allows for maintenance of mitochondrial NAD(+) pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD(+) consumption and establishing a buffer of NAD(+) precursors in differentiated cells. PMID: 28991266 [PubMed - indexed for MEDLINE]

Related Articles Volatile organic compounds in gastrointestinal stromal tumour tissue originating from patient-derived xenografts. J Breath Res. 2017 Jun 29;11(3):037101 Authors: Wawrzyniak R, Woźniak A, Gebreyohannes YK, Dykcik B, Schöffski P, Markuszewski MJ Abstract Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and localize mainly in the stomach or small intestine. The metabolomic signatures of GISTs driven by different KIT gene mutations remain undiscovered and unexplored. The main aim of this pilot study was to determine and compare metabolomic profiles in GIST xenograft models with different genetic backgrounds. Metabolomic profiling using gas chromatography coupled with mass spectrometry followed by univariate and multivariate statistical analyses was applied to select metabolites that differentiated the GIST models studied. The significant differences observed in the metabolites were mainly derived from glycolysis, the citric acid cycle and glutamine and lipid metabolism. The obtained results may suggest variable metabolomic signatures of tumours, possibly related to the different underlying, specific KIT gene mutations and with potential implications for the biological behaviour and natural course of this rare disease. This study constitutes a proof of concept in GISTs and reveals the potential of the metabolomic approach in orphan malignancies. PMID: 28416775 [PubMed - indexed for MEDLINE]

Related Articles Traditional and novel tools to probe the mitochondrial metabolism in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2017 Mar;9(2): Authors: Zhang Y, Avalos JL Abstract Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer. Therefore, there is great interest in understanding mitochondrial metabolism and the complex relationship it has with other cellular processes. A large number of studies on mitochondrial metabolism have been conducted in the last 50 years, taking a broad range of approaches. In this review, we summarize and discuss the most commonly used tools that have been used to study different aspects of the metabolism of mitochondria: ranging from dyes that monitor changes in the mitochondrial membrane potential and pharmacological tools to study respiration or ATP synthesis, to more modern tools such as genetically encoded biosensors and trans-omic approaches enabled by recent advances in mass spectrometry, computation, and other technologies. These tools have allowed the large number of studies that have shaped our current understanding of mitochondrial metabolism. WIREs Syst Biol Med 2017, 9:e1373. doi: 10.1002/wsbm.1373 For further resources related to this article, please visit the WIREs website. PMID: 28067471 [PubMed - indexed for MEDLINE]

Related Articles Forthcoming Challenges in Mycotoxins Toxicology Research for Safer Food-A Need for Multi-Omics Approach. Toxins (Basel). 2017 Jan 04;9(1): Authors: Dellafiora L, Dall'Asta C Abstract The presence of mycotoxins in food represents a severe threat for public health and welfare, and poses relevant research challenges in the food toxicology field. Nowadays, food toxicologists have to provide answers to food-related toxicological issues, but at the same time they should provide the appropriate knowledge in background to effectively support the evidence-based decision-making in food safety. Therefore, keeping in mind that regulatory actions should be based on sound scientific findings, the present opinion addresses the main challenges in providing reliable data for supporting the risk assessment of foodborne mycotoxins. PMID: 28054977 [PubMed - indexed for MEDLINE]

Related Articles Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy. Neonatology. 2016;110(4):296-302 Authors: Ahearne CE, Denihan NM, Walsh BH, Reinke SN, Kenny LC, Boylan GB, Broadhurst DI, Murray DM Abstract BACKGROUND: A 1H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. OBJECTIVE: To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. METHODS: From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. RESULTS: Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ2 = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). CONCLUSIONS: The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score. PMID: 27486995 [PubMed - indexed for MEDLINE]

Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients. EBioMedicine. 2017 Oct 31;: Authors: Hallan S, Afkarian M, Zelnick LR, Kestenbaum B, Sharma S, Saito R, Darshi M, Barding G, Raftery D, Ju W, Kretzler M, Sharma K, de Boer IH Abstract Chronic kidney disease (CKD) is a public health problem with very high prevalence and mortality. Yet, there is a paucity of effective treatment options, partly due to insufficient knowledge of underlying pathophysiology. We combined metabolomics (GCMS) with kidney gene expression studies to identify metabolic pathways that are altered in adults with non-diabetic stage 3-4 CKD versus healthy adults. Urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed significantly in CKD patients versus controls (estimate range-68% to +113%). Pathway analysis revealed that the citric acid cycle was the most significantly affected, with urinary excretion of citrate, cis-aconitate, isocitrate, 2-oxoglutarate and succinate reduced by 40-68%. Reduction of the citric acid cycle metabolites in urine was replicated in an independent cohort. Expression of genes regulating aconitate, isocitrate, 2-oxoglutarate and succinate were significantly reduced in kidney biopsies. We observed increased urine citrate excretion (+74%, p=0.00009) and plasma 2-oxoglutarate concentrations (+12%, p=0.002) in CKD patients during treatment with a vitamin-D receptor agonist in a randomized trial. In conclusion, urinary excretion of citric acid cycle metabolites and renal expression of genes regulating these metabolites were reduced in non-diabetic CKD. This supports the emerging view of CKD as a state of mitochondrial dysfunction. PMID: 29128444 [PubMed - as supplied by publisher]

Investigation of novel metabolites potentially involved in the pathogenesis of coronary heart disease using a UHPLC-QTOF/MS-based metabolomics approach. Sci Rep. 2017 Nov 10;7(1):15357 Authors: Li Y, Zhang D, He Y, Chen C, Song C, Zhao Y, Bai Y, Wang Y, Pu J, Chen J, Yang Y, Dou K Abstract Coronary heart disease (CHD) is associated with complex metabolic disorders, but its molecular aetiology remains unclear. Using a novel nontargeted metabolomics approach, we explored the global metabolic perturbation profile for CHD. Blood samples from 150 patients with severe obstructive CHD and 150 angiographically normal controls were collected. Metabolic fingerprinting was performed by ultra-high performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) technique. After adjusting for CHD traditional risk factors and metabolic batch, a comprehensive list of 105 metabolites was found to be significantly altered in CHD patients. Among the metabolites identified, six metabolites were discovered to have the strongest correlation with CHD after adjusting for multiple testing: palmitic acid (β = 0.205; p < 0.0001), linoleic acid (β = 0.133; p < 0.0001), 4-pyridoxic acid (β = 0.142; p < 0.0001), phosphatidylglycerol (20:3/2:0) (β = 0.287; p < 0.0001), carnitine (14:1) (β = 0.332; p < 0.0001) and lithocholic acid (β = 0.224; p < 0.0001); of these, 4-pyridoxic acid, lithocholic acid and phosphatidylglycerol (20:3/2:0) were, to the best of our knowledge, first reported in this study. A logistic regression model further quantified their positive independent correlations with CHD. In conclusion, this study surveyed a broad panel of nontargeted metabolites in Chinese CHD populations and identified novel metabolites that are potentially involved in CHD pathogenesis. PMID: 29127404 [PubMed - in process]

Quantum Chemical Fragment Precursor Tests: Accelerating de novo annotation of tandem mass spectra. Anal Chim Acta. 2017 Dec 01;995:52-64 Authors: Janesko BG, Li L, Mensing R Abstract Tandem mass spectrometry is widely used to assign and distinguish chemical structures in proteomics, metabolomics, lipidomics, and many other areas. Spectral annotation remains a major bottleneck. Our "Quantum Chemical Fragment Precursor Tests" (QC-FPT) approach brings the accuracy and generality of modern quantum chemistry to combinatorial-search-based computer-aided spectral annotation. QC-FPT takes as input the dominant fragment peaks from a particular experiment, and one or more chemically reasonable hypotheses for the precursor ion's three-dimensional structure. The algorithm automatically generates possible precursor ion fragmentations matching the target experimental peaks, uses quantum chemistry calculations (geometry optimization with gas-phase semiempirical or density functional theory calculations) to predict each neutral or charged fragment's structure and energy, and reports the thermodynamically feasible predicted fragment assignments. Applications demonstrate that QC-FPT recovers known spectral annotations, can handle multiple ionization and fragmentation methods and adducts, and can capture some fragment rearrangements. We apply QC-FPT to assign previously unassigned peaks in an experimental LC-ESI-MS(2) spectrum of dimethylarsinothioyl glutathione (Yehiayan et al., Chem. Res. Toxicol. 2014, 27, 754-764), and to a hypothetical experiment distinguishing two isomeric candidates for an "unknown" pesticide's experimental LC-ESI-MS(2) spectrum. Our results suggest QC-FPT is a practical tool to sharpen and refine the chemical intuition of experimentalists engaged in the laborious process of annotating tandem mass spectra. PMID: 29126481 [PubMed - in process]

Optimization of GC/TOF MS analysis conditions for assessing host-gut microbiota metabolic interactions: Chinese rhubarb alters fecal aromatic amino acids and phenol metabolism. Anal Chim Acta. 2017 Dec 01;995:21-33 Authors: Yin S, Guo P, Hai D, Xu L, Shu J, Zhang W, Khan MI, Kurland IJ, Qiu Y, Liu Y Abstract In this paper, an optimized method based on gas chromatography/time-of-flight mass spectrometry (GC-TOFMS) platform has been developed for the analysis of gut microbial-host related co-metabolites in fecal samples. The optimization was performed with proportion of chloroform (C), methanol (M) and water (W) for the extraction of specific metabolic pathways of interest. Loading Bi-plots from the PLS regression model revealed that high concentration of chloroform emphasized the extraction of short chain fatty acids and TCA intermediates, while the higher concentration of methanol emphasized indole and phenyl derivatives. Low level of organic solution emphasized some TCA intermediates but not for indole and phenyl species. The highest sum of the peak area and the distribution of metabolites corresponded to the extraction of methanol/chloroform/water of 225:75:300 (v/v/v), which was then selected for method validation and utilized in our application. Excellent linearity was obtained with 62 reference standards representing different classes of gut microbial-host related co-metabolites, with correlation coefficients (r(2)) higher than 0.99. Limit of detections (LODs) and limit of qualifications (LOQs) for these standards were below 0.9 nmol and 1.6 nmol, respectively. The reproducibility and repeatability of the majority of tested metabolites in fecal samples were observed with RSDs lower than 15%. Chinese rhubarb-treated rats had elevated indole and phenyl species, and decreased levels of polyamine such as putrescine, and several amino acids. Our optimized method has revealed host-microbe relationships of potential importance for intestinal microbial metabolite receptors such as pregnane X receptor (PXR) and aryl hydrocarbon receptor (AHR) activity, and for enzymes such as ornithine decarboxylase (ODC). PMID: 29126478 [PubMed - in process]

Combination of HPLC with organic and inorganic mass spectrometry to study the metabolic response of the clam Scrobicularia plana to arsenic exposure. Electrophoresis. 2017 Nov 10;: Authors: Rodríguez-Moro G, García-Barrera T, Trombini C, Blasco J, Gómez-Ariza JL Abstract Arsenic is a toxic element extensively studied in the marine environment due to differential toxicological effects of inorganic and organic species. In the present work, the bivalve Scrobicularia plana was exposed to As(V) (10 and 100 μg·L(-1) ) for 14 days to evaluate the metabolic perturbations caused by this element. Arsenic speciation and metabolomic analysis were performed in the digestive gland of the bivalve using two complementary analytical platforms based on inorganic and organic mass spectrometry. It has been observed the greater presence of the innocuous specie arsenobetaine produced in this organism as defense mechanism against arsenic toxicity, although significant concentrations of methylated and inorganic arsenic were also present, depending on the level of arsenic in aqueous media. Complementarily, a metabolomic study based on mass spectrometry and statistical discriminant analysis allows a good classification of samples associated to low and high As(V) exposure in relation to controls. About 15 metabolites suffer significant changes of expression by the presence of As(V): amino acids, nucleotides, energy-related metabolites, free fatty acids, phospholipids and triacylglycerides, which can be related to membrane structural and functional damage. In addition, perturbation of the methylation cycle, associated with the increase of homocysteine and methionine was observed, which enhance the methylation of toxic inorganic arsenic to less toxic dimethylarsenic. This article is protected by copyright. All rights reserved. PMID: 29125650 [PubMed - as supplied by publisher]

Metabolite Profiling of Peppers of Various Colors Reveals Relationships Between Tocopherol, Carotenoid, and Phytosterol Content. J Food Sci. 2017 Nov 10;: Authors: Kim TJ, Choi J, Kim KW, Ahn SK, Ha SH, Choi Y, Park NI, Kim JK Abstract Peppers are widely consumed in Korea; the varietal development of peppers with increased content of beneficial plant metabolites is, therefore, of considerable interest. This requires a comprehensive understanding of the metabolic profile of pepper plants and the factors affecting this profile. To this end, we determined the content of various metabolites, such as hydrophilic and lipophilic compounds, phenolic acids, carotenoids, and capsaicinoids in peppers of various colors (green, red, pale green, and violet peppers) and in a high-pungency (green) pepper. We also performed principal component analysis (PCA), Pearson's correlation analysis, and hierarchical clustering analysis (HCA) to determine the relationships among these metabolites in peppers. PCA results indicated no significant variances among the 3 sample replicates. The HCA showed correlations between the metabolites resulting from common or closely linked biosynthesis pathways. Our results showed that carotenoids correlated positively with tocopherols and negatively with phytosterols; our findings also indicated a close relationship between the methylerythritol 4-phosphate and mevalonic acid biosynthesis pathways, providing evidence in favor of an earlier hypothesis regarding crosstalk across the chloroplast membrane. We, thus, demonstrate that metabolic profiling combined with multivariate analysis is a useful tool for analyzing metabolic networks. PRACTICAL APPLICATION: A total of 71 metabolites were measured in 5 peppers of different colors. The metabolic profiling with multivariate analysis revealed that tocopherol content had a positive correlation with the carotenoid content and a negative correlation with the phytosterol content. The results of this study may help in breeding programs to produce new germplasm with enhanced nutritional quality. PMID: 29125620 [PubMed - as supplied by publisher]

Early Response Monitoring Following Radiation Therapy by Using [(18)F]FDG and [(11)C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration. Molecules. 2017 Nov 10;22(11): Authors: Chung YH, Tsai CK, Wang CC, Chen HM, Lu KY, Chiu H, Lin YC, Yen TC, Lin G Abstract We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and [(11)C]acetate ([(11)C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [(18)F]FDG and [(11)C]ACT PET were performed before and following irradiation (RT, 15Gy) for transgenic adenocarcinoma of mouse prostate xenografts. The underlying metabolomics alterations of tumor tissues were analyzed by using ex vivo NMR. The [(18)F]FDG total lesion glucose (TLG) of the tumor significant increased in the RT group at Days 1 and 3 post-irradiation, compared with the non-RT group (p < 0.05). The [(11)C]ACT maximum standard uptake value (SUVmax) in RT (0.83 ± 0.02) and non-RT groups (0.85 ± 0.07) were not significantly different (p > 0.05). The ex vivo NMR analysis showed a 1.70-fold increase in glucose and a 1.2-fold increase in acetate in the RT group at Day 3 post-irradiation (p < 0.05). Concordantly, the expressions of cytoplasmic acetyl-CoA synthetase in the irradiated tumors was overexpressed at Day 3 post-irradiation (p < 0.05). Therefore, TLG of [(18)F]FDG in vivo PET images can map early treatment response following irradiation and be a promising prognostic indicator in a longitudinal preclinical study. The underlying metabolic alterations was not reflected by the [(11)C]ACT PET. PMID: 29125557 [PubMed - in process]

Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach. J Trop Med. 2017;2017:2189814 Authors: Ahmad SJ, Abdul Rahim MBH, Baharum SN, Baba MS, Zin NM Abstract Natural products continue to play an important role as a source of biologically active substances for the development of new drug. Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process. Metabolomics is an emerging "omics" technology in systems biology study which integrated in process of discovering drug from natural products. Metabolomics approach in finding novel therapeutics agent for malaria offers dereplication step in screening phase to shorten the process. The highly sensitive instruments, such as Liquid Chromatography-Mass Spectrophotometry (LC-MS), Gas Chromatography-Mass Spectrophotometry (GC-MS), and Nuclear Magnetic Resonance ((1)H-NMR) spectroscopy, provide a wide range of information in the identification of potentially bioactive compounds. The current paper reviews concepts of metabolomics and its application in drug discovery of malaria treatment as well as assessing the antimalarial activity from natural products. Metabolomics approach in malaria drug discovery is still new and needs to be initiated, especially for drug research in Malaysia. PMID: 29123551 [PubMed]

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes. Sci Rep. 2017 Nov 09;7(1):15190 Authors: Ward MS, Flemming NB, Gallo LA, Fotheringham AK, McCarthy DA, Zhuang A, Tang PH, Borg DJ, Shaw H, Harvie B, Briskey DR, Roberts LA, Plan MR, Murphy MP, Hodson MP, Forbes JM Abstract Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown. PMID: 29123192 [PubMed - in process]