PubMed

Related Articles Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice. PLoS One. 2017;12(2):e0172912 Authors: den Hartigh LJ, Wang S, Goodspeed L, Wietecha T, Houston B, Omer M, Ogimoto K, Subramanian S, Gowda GA, O'Brien KD, Kaiyala KJ, Morton GJ, Chait A Abstract BACKGROUND: Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance. OBJECTIVE: We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism. METHODS: Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured. RESULTS: By design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation. CONCLUSIONS: These results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss. PMID: 28245284 [PubMed - in process]

Related Articles Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses. PLoS One. 2017;12(2):e0173069 Authors: Benevenuto RF, Agapito-Tenfen SZ, Vilperte V, Wikmark OG, van Rensburg PJ, Nodari RO Abstract Some genetically modified (GM) plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA) analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses. PMID: 28245233 [PubMed - in process]

Related Articles Impact of the Pd2Spermine chelate on osteosarcoma metabolism: an NMR metabolomics study. J Proteome Res. 2017 Feb 28;: Authors: Lamego I, Marques MP, Duarte IF, Martins AS, Oliveira H, Gil AM Abstract A metabolomics study of Pd2Spermine(Spm) on osteosarcoma MG-63 and osteoblastic HOb cells is presented, to assess the impact of the potential palladium drug on cell metabolism compared to cisplatin (cDDP). In spite of its higher cytotoxicity, Pd2Spm induced lower (and reversible) metabolic impact in MG-63 cells and absence of apoptosis; conversely, it induced significant deviations in osteoblastic amino acid metabolism. However, when in combination with doxorubicin and methotrexate, Pd2Spm induced strong metabolic deviations on lipids, choline compounds, amino acids, nucleotides and compounds related to antioxidative mechanisms (e.g. glutathione, inositol, hypoxanthine), similarly to the cDDP cocktail. Synergetic effects included triggering of lipid biosynthesis by Pd2Spm in the presence of doxorubicin (and reinforced by methotrexate) and changes in the glycosylation substrate uridine diphosphate acetylgalactosamine and methionine and serine metabolisms. This work provides promising results relating to the impact of Pd2Spm on osteosarcoma cellular metabolism, particularly in drug combination protocols. Lipid metabolism, glycosylation and amino acid metabolisms emerge as relevant features for targeted studies to further understand a potential anti-cancer mechanism of combined Pd2Spm. PMID: 28244322 [PubMed - as supplied by publisher]

Related Articles Early Effect of Amyloid β-Peptide on Hippocampal and Serum Metabolism in Rats Studied by an Integrated Method of NMR-Based Metabolomics and ANOVA-Simultaneous Component Analysis. Biomed Res Int. 2017;2017:3262495 Authors: Du Y, Zheng H, Xia H, Zhao L, Hu W, Bai G, Yan Z, Gao H Abstract Amyloid β (Aβ) deposition has been implicated in the pathogenesis of Alzheimer's disease. However, the early effect of Aβ deposition on metabolism remains unclear. In the present study, thus, we explored the metabolic changes in the hippocampus and serum during first 2 weeks of Aβ25-35 injection in rats by using an integrated method of NMR-based metabolomics and ANOVA-simultaneous component analysis (ASCA). Our results show that Aβ25-35 injection, time, and their interaction had statistically significant effects on the hippocampus and serum metabolome. Furthermore, we identified key metabolites that mainly contributed to these effects. After Aβ25-35 injection from 1 to 2 weeks, the levels of lactate, N-acetylaspartate, creatine, and taurine were decreased in rat hippocampus, while an increase in lactate and decreases in LDL/VLDL and glucose were observed in rat serum. Therefore, we suggest that the reduction in energy and lipid metabolism as well as an increase in anaerobic glycolysis may occur at the early stage of Aβ25-35 deposition. PMID: 28243597 [PubMed - in process]

Related Articles Metabolomic analysis of human oral cancer cells with adenylate kinase 2 or phosphorylate glycerol kinase 1 inhibition. J Cancer. 2017;8(2):298-304 Authors: Ji EH, Cui L, Yuan X, Cheng S, Messadi D, Yan X, Hu S Abstract The purpose of this study was to use liquid chromatography-mass spectrometry (LC-MS) with XCMS for a quantitative metabolomic analysis of UM1 and UM2 oral cancer cells after knockdown of metabolic enzyme adenylate kinase 2 (AK2) or phosphorylate glycerol kinase 1 (PGK1). UM1 and UM2 cells were initially transfected with AK2 siRNA, PGK1 siRNA or scrambled control siRNA, and then analyzed with LC-MS for metabolic profiles. XCMS analysis of the untargeted metabolomics data revealed a total of 3200-4700 metabolite features from the transfected UM1 or UM2 cancer cells and 369-585 significantly changed metabolites due to AK2 or PGK1 suppression. In addition, cluster analysis showed that a common group of metabolites were altered by AK2 knockdown or by PGK1 knockdown between the UM1 and UM2 cells. However, the set of significantly changed metabolites due to AK2 knockdown was found to be distinct from those significantly changed by PGK1 knockdown. Our study has demonstrated that LC-MS with XCMS is an efficient tool for metabolomic analysis of oral cancer cells, and knockdown of different genes results in distinct changes in metabolic phenotypes in oral cancer cells. PMID: 28243334 [PubMed - in process]

Related Articles The Role of Sarcosine, Uracil, and Kynurenic Acid Metabolism in Urine for Diagnosis and Progression Monitoring of Prostate Cancer. Metabolites. 2017 Feb 23;7(1): Authors: Gkotsos G, Virgiliou C, Lagoudaki I, Sardeli C, Raikos N, Theodoridis G, Dimitriadis G Abstract The aim of this pilot study is to evaluate sarcosine, uracil, and kynurenic acid in urine as potential biomarkers in prostate cancer detection and progression monitoring. Sarcosine, uracil, and kynurenic acid were measured in urine samples of 32 prostate cancer patients prior to radical prostatectomy, 101 patients with increased prostate-specific antigen prior to ultrasonographically-guided prostatic biopsy collected before and after prostatic massage, and 15 healthy volunteers (controls). The results were related to histopathologic data, Gleason score, and PSA (Prostate Specific Antigen). Metabolites were measured after analysis of urine samples with Ultra-High Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) instrumentation. Multivariate, nonparametric statistical tests including receiver operating characteristics analyses, one-way analysis of variance (Kruskal-Wallis test), parametric statistical analysis, and Pearson correlation, were performed to evaluate diagnostic performance. Decreased median sarcosine and kynurenic acid and increased uracil concentrations were observed for patients with prostate cancer compared to participants without malignancy. Results showed that there was no correlation between the concentration of the studied metabolites and the cancer grade (Gleason score <7 vs. ≥7) and the age of the patients. Evaluation of biomarkers by ROC (Receiving Operating Characteristics) curve analysis showed that differentiation of prostate cancer patients from participants without malignancy was not enhanced by sarcosine or uracil levels in urine. In contrast to total PSA values, kynurenic acid was found a promising biomarker for the detection of prostate cancer particularly in cases where collection of urine samples was performed after prostatic massage. Sarcosine and uracil in urine samples of patients with prostate cancer were not found as significant biomarkers for the diagnosis of prostate cancer. None of the three metabolites can be used reliably for monitoring the progress of the disease. PMID: 28241496 [PubMed - in process]

Related Articles Impact of Exercise and Aging on Rat Urine and Blood Metabolome. An LC-MS Based Metabolomics Longitudinal Study. Metabolites. 2017 Feb 23;7(1): Authors: Deda O, Gika HG, Taitzoglou I, Raikos Ν, Theodoridis G Abstract Aging is an inevitable condition leading to health deterioration and death. Regular physical exercise can moderate the metabolic phenotype changes of aging. However, only a small number of metabolomics-based studies provide data on the effect of exercise along with aging. Here, urine and whole blood samples from Wistar rats were analyzed in a longitudinal study to explore metabolic alterations due to exercise and aging. The study comprised three different programs of exercises, including a life-long protocol which started at the age of 5 months and ended at the age of 21 months. An acute exercise session was also evaluated. Urine and whole blood samples were collected at different time points and were analyzed by LC-MS/MS (Liquid Chromatography-tandem Mass Spectrometry). Based on their metabolic profiles, samples from trained and sedentary rats were differentiated. The impact on the metabolome was found to depend on the length of exercise period with acute exercise also showing significant changes. Metabolic alterations due to aging were equally pronounced in sedentary and trained rats in both urine and blood analyzed samples. PMID: 28241477 [PubMed - in process]

Related Articles Metabolic Profiling as a Screening Tool for Cytotoxic Compounds: Identification of 3-Alkyl Pyridine Alkaloids from Sponges Collected at a Shallow Water Hydrothermal Vent Site North of Iceland. Mar Drugs. 2017 Feb 22;15(2): Authors: Einarsdottir E, Magnusdottir M, Astarita G, Köck M, Ögmundsdottir HM, Thorsteinsdottir M, Rapp HT, Omarsdottir S, Paglia G Abstract Twenty-eight sponge specimens were collected at a shallow water hydrothermal vent site north of Iceland. Extracts were prepared and tested in vitro for cytotoxic activity, and eight of them were shown to be cytotoxic. A mass spectrometry (MS)-based metabolomics approach was used to determine the chemical composition of the extracts. This analysis highlighted clear differences in the metabolomes of three sponge specimens, and all of them were identified as Haliclona (Rhizoniera) rosea (Bowerbank, 1866). Therefore, these specimens were selected for further investigation. Haliclona rosea metabolomes contained a class of potential key compounds, the 3-alkyl pyridine alkaloids (3-APA) responsible for the cytotoxic activity of the fractions. Several 3-APA compounds were tentatively identified including haliclamines, cyclostellettamines, viscosalines and viscosamines. Among these compounds, cyclostellettamine P was tentatively identified for the first time by using ion mobility MS in time-aligned parallel (TAP) fragmentation mode. In this work, we show the potential of applying metabolomics strategies and in particular the utility of coupling ion mobility with MS for the molecular characterization of sponge specimens. PMID: 28241423 [PubMed - in process]

Related Articles Bioprospecting of Turbinaria Macroalgae as a Potential Source of Health Protective Compounds. Chem Biodivers. 2017 Feb;14(2): Authors: Stranska-Zachariasova M, Kurniatanty I, Gbelcova H, Jiru M, Rubert J, Nindhia TG, D'Acunto CW, Sumarsono SH, Tan MI, Hajslova J, Ruml T Abstract The present study aims to focus on the bioprospecting of marine macroalgae of Turbinaria species, plenteous biomass of the world ocean. Three types of solvents, i.e., H2 O, MeOH/H2 O (80:20, v/v) and hexane/i-PrOH (50:50, v/v), were used for extraction. Both the biological activity and the pattern of present chemicals were characterized. For the cell proliferation assay, the human embryonic kidney 293 cells, cervix/breast/pancreatic adenocarcinoma, and osteosarcoma cells were used. For the antioxidant activity determination, both intracellular assay with human embryonic kidney and cervix adenocarcinoma cells, as well as the biochemical DPPH test, were employed. To complete the information about macroalgae composition, organic compounds were characterized by the liquid chromatography coupled with high resolution tandem mass spectrometry. Attention was concentrated mainly on the lipidomic profile characterization. In spite the fact that any significant antiproliferative effect was not observed for cancer cells, both the Turbinaria species were shown to be good protectors against the oxidative stress of the non-cancer cells. Most of the antioxidants were determined in the hexane/i-PrOH extract. As regards the lipids identified, most of them belonged to the triacylglycerols followed by sphingomyelins, diacylglycerols, and polar (lyso)phospholipids. Additionally to fatty acids with 14, 16 and 18 carbons, also those with odd carbon numbers were frequently present. PMID: 27936316 [PubMed - indexed for MEDLINE]

Related Articles Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS. Sci Rep. 2016 Apr 14;6:23296 Authors: Jansen BC, Bondt A, Reiding KR, Lonardi E, de Jong CJ, Falck D, Kammeijer GS, Dolhain RJ, Rombouts Y, Wuhrer M Abstract Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy. PMID: 27075729 [PubMed - indexed for MEDLINE]

Domain-targeted metabolomics delineates the heterocycle assembly steps of colibactin biosynthesis. J Am Chem Soc. 2017 Feb 27;: Authors: Trautman E, Healy AR, Shine E, Herzon SB, Crawford JM Abstract Modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) comprise giant multidomain enzymes responsible for the "assembly line" biosynthesis of many genetically-encoded small molecules. Site-directed mutagenesis, protein biochemical, and structural studies have focused on elucidating the catalytic mechanisms of individual multidomain proteins and protein domains within these megasynthases. Probing their functions at the cellular level typically has invoked the complete deletion (or overexpression) of multidomain-encoding genes or combinations of genes and comparing those mutants to a control pathway. Here, we describe a "domain-targeted" metabolomic strategy that combines genome editing with pathway analysis to probe the functions of individual PKS and NRPS catalytic domains at the cellular metabolic level. We apply the approach to the bacterial colibactin pathway, a genotoxic PKS-NRPS hybrid pathway found in certain E. coli. The pathway produces precolibactins, which are converted to colibactins by a dedicated peptidase, ClbP. Domain-targeted metabolomics enabled the characterization of "multidomain signatures," or functional readouts of PKS-NRPS domain contributions to the pathway-dependent metabolome. These multidomain signatures provided experimental support for individual domain contributions to colibactin biosynthesis and delineated the assembly line timing events of colibactin heterocycle formation. The analysis also led to the structural characterization of two reactive precolibactin metabolites. We demonstrate the fate of these reactive intermediates in the presence and absence of ClbP, which dictates the formation of distinct product groups resulting from alternative cyclization cascades. In the presence of the peptidase, the reactive intermediates are converted to a known genotoxic scaffold providing metabolic support of our mechanistic model for colibactin-induced genotoxicity. Domain-targeted metabolomics could be more widely used to characterize NRPS-PKS pathways with unprecedented genetic and metabolic precision. PMID: 28240912 [PubMed - as supplied by publisher]

Related Articles Training in metabolomics research. II. Processing and statistical analysis of metabolomics data, metabolite identification, pathway analysis, applications of metabolomics and its future. J Mass Spectrom. 2016 Aug;51(8):535-548 Authors: Barnes S, Benton HP, Casazza K, Cooper SJ, Cui X, Du X, Engler J, Kabarowski JH, Li S, Pathmasiri W, Prasain JK, Renfrow MB, Tiwari HK Abstract Metabolomics, a systems biology discipline representing analysis of known and unknown pathways of metabolism, has grown tremendously over the past 20 years. Because of its comprehensive nature, metabolomics requires careful consideration of the question(s) being asked, the scale needed to answer the question(s), collection and storage of the sample specimens, methods for extraction of the metabolites from biological matrices, the analytical method(s) to be employed and the quality control of the analyses, how collected data are correlated, the statistical methods to determine metabolites undergoing significant change, putative identification of metabolites and the use of stable isotopes to aid in verifying metabolite identity and establishing pathway connections and fluxes. This second part of a comprehensive description of the methods of metabolomics focuses on data analysis, emerging methods in metabolomics and the future of this discipline. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 28239968 [PubMed - in process]

Related Articles Training in metabolomics research. II. Processing and statistical analysis of metabolomics data, metabolite identification, pathway analysis, applications of metabolomics and its future. J Mass Spectrom. 2016 Aug;51(8):ii-iii Authors: Barnes S, Benton HP, Casazza K, Cooper SJ, Cui X, Du X, Engler J, Kabarowski JH, Li S, Pathmasiri W, Prasain JK, Renfrow MB, Tiwari HK Abstract Metabolomics is perhaps the most challenging of the -omics fields, given the complexity of an organism's metabolome and the rapid rate at which it changes. When one sets out to study metabolism there are numerous dynamic variables that can influence metabolism that must be considered. Recognizing the experimental challenges confronting researchers who undertake metabolism studies, workshops like the one at University of Alabama at Birmingham have been established to offer instructional guidance. A summary of the UAB course training materials is being published as a two-part Special Feature Tutorial. In this month's Part I the authors discuss details of good experimental design and sample collection and handling. In an upcoming Part II, the authors discuss in detail the various aspects of data analysis. PMID: 28239964 [PubMed - in process]

Related Articles Genotype-by-environment effect on bioactive compounds in strawberry (Fragaria x ananassa Duch.). J Sci Food Agric. 2017 Feb 27;: Authors: Palmieri L, Masuero D, Martinatti P, Baratto G, Martens S, Vrhovsek U Abstract BACKGROUND: The relative contribute assessment of the genotype, the environment and the genotype-by-environmental (G x E) interaction to the variety performance is necessary to determine their adaptation capacity. RESULTS: The influence of temperature, UV-irradiation and sunshine duration on quality and fruits composition was investigated in nine strawberry cultivars grown at three different altitudes. The UV-radiation intensity affected the pH and the sugar content that were higher for most of the varieties at low altitudes where the total titratable acidity (TTA) was less. Fruits from plants grown at low elevation generally had higher benzoic acid derivative content. Significant correlation was found between phenylpropanoids content and UV-radiation and sunshine duration. The flavone class seems to be affected most from the variety effect contrary to flavonols and ellagitannins that are highly affected from environment. The accumulation of a number of secondary metabolites in strawberry fruits grown in unusual environmental condition highlighted an acclimation effects as plants response to abiotic stress. Finally only for "Sveva" and "Marmolada" the genetic factor seems to be more influent for all parameters considered. CONCLUSION: This "plant environmental metabolomics" approach was successfully used to assess the phenotypic plasticity of our varieties that showed different magnitudes in terms of the relationship between environmental conditions and the accumulation of healthy compounds. PMID: 28239870 [PubMed - as supplied by publisher]

Related Articles Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize. Environ Sci Eur. 2017;29(1):6 Authors: Mesnage R, Arno M, Séralini GE, Antoniou MN Abstract BACKGROUND: A previous 2-year rat feeding trial assessing potential toxicity of NK603 Roundup-tolerant genetically modified maize revealed blood and urine biochemical changes indicative of liver and kidney pathology. In an effort to obtain deeper insight into these findings, molecular profiling of the liver and kidneys from the same animals was undertaken. RESULTS: Transcriptomics showed no segregation of NK603 maize and control feed groups with false discovery rates ranging from 43 to 83% at a cut-off p value of 1%. Changes in gene expression were not reflective of liver and kidney toxic effects. Metabolomics identified 692 and 673 metabolites in kidney and liver, respectively. None of the statistically significant disturbances detected (12-56 for different test groups) survived a false discovery rate analysis. Differences in these metabolites between individual animals within a group were greater than the effect of test diets, which prevents a definitive conclusion on either pathology or safety. CONCLUSIONS: Even if the biological relevance of the statistical differences presented in this study is unclear, our results are made available for scrutiny by the scientific community and for comparison in future studies investigating potential toxicological properties of the NK603 corn. PMID: 28239534 [PubMed - in process]

Related Articles Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging (Albany NY). 2017 Feb 26;: Authors: Zhou J, Chong SY, Lim A, Singh BK, Sinha RA, Salmon AB, Yen PM Abstract Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of ATG3 and ATG12-ATG5. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, PINK1 and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle vs. heart during aging. PMID: 28238968 [PubMed - as supplied by publisher]

Related Articles Tryptophan and purine metabolites are consistently upregulated in the urinary metabolome of patients diagnosed with gestational diabetes mellitus throughout pregnancy: A longitudinal metabolomics study of Chinese pregnant women part 2. Clin Chim Acta. 2017 Feb 23;: Authors: Law KP, Han TL, Mao X, Zhang H Abstract BACKGROUND: Gestational diabetes mellitus (GDM) is a pathological state of glucose intolerance associated with adverse pregnancy outcomes and an increased risk of developing maternal type 2 diabetes later in life. The mechanisms underlying GDM development are not fully understood. We examined the pathophysiology of GDM through comprehensive metabolic profiling of maternal urine, using participants from a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM. METHODS: Based on ultra-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the differences in the urinary metabolome of GDM cases and healthy controls over the course of pregnancy. Multilevel statistical approaches were employed to address the complex metabolomic data obtained from a longitudinal cohort. RESULTS: The results indicated that tryptophan and purine metabolism was associated with GDM. The tryptophan-kynurenine pathway was activated in the GDM subjects before placental hormones or the fetoplacental unit could have produced any physiological effect. Hypoxanthine, xanthine, xanthosine, and 1-methylhypoxanthine were all elevated in the urine metabolome of subjects with GDM. Catabolism of purine nucleosides leads ultimately to the production of uric acid, which discriminated the subjects with GDM from controls. CONCLUSIONS: The results support the notion that GDM may be a predisposed condition, or prediabetic state, which is manifested during pregnancy. This challenges the conventional view of the pathogenesis of GDM, which assumes placental hormones are the major causes of insulin resistance in GDM. PMID: 28238935 [PubMed - as supplied by publisher]

Related Articles Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus. Biochem Biophys Res Commun. 2017 Feb 23;: Authors: Vargas-Muñiz JM, Renshaw H, Waitt G, Soderblom EJ, Moseley MA, Palmer JM, Juvvadi PR, Keller NP, Steinbach WJ Abstract Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. Deletion of the A. fumigatus septin aspB increases susceptibility to the echinocandin antifungal caspofungin. However, how AspB mediates this response to caspofungin is unknown. Here, we characterized the AspB interactome under basal conditions and after exposure to a clinically relevant concentration of caspofungin. While A. fumigatus AspB interacted with 334 proteins, including kinases, cell cycle regulators, and cell wall synthesis-related proteins under basal growth conditions, caspofungin exposure altered AspB interactions. A total of 69 of the basal interactants did not interact with AspB after exposure to caspofungin, and 54 new interactants were identified following caspofungin exposure. We generated A. fumigatus deletion strains for 3 proteins (ArpB, Cyp4, and PpoA) that only interacted with AspB following exposure to caspofungin that were previously annotated as induced after exposure to antifungal agents, yet only PpoA was implicated in the response to caspofungin. Taken together, we defined how the septin AspB interactome is altered in the presence of a clinically relevant antifungal. PMID: 28238781 [PubMed - as supplied by publisher]

Related Articles Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection. EBioMedicine. 2017 Feb 21;: Authors: Burke TW, Henao R, Soderblom E, Tsalik EL, Thompson JW, McClain MT, Nichols M, Nicholson BP, Veldman T, Lucas JE, Moseley MA, Turner RB, Lambkin-Williams R, Hero AO, Woods CW, Ginsburg GS Abstract Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza A/H3N2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection. Unbiased proteomic discovery analysis identified 3285 peptides corresponding to 438 unique proteins, and revealed that infection with H3N2 induces significant alterations in protein expression. These include proteins involved in acute inflammatory response, innate immune response, and the complement cascade. These data provide insights into the nature of the biological response to viral infection of the upper respiratory tract, and the proteins that are dysregulated by viral infection form the basis of signature that accurately classifies the infected state. Verification of this signature using targeted mass spectrometry in independent cohorts of subjects challenged with influenza or rhinovirus demonstrates that it performs with high accuracy (0.8623 AUROC, 75% TPR, 97.46% TNR). With further development as a clinical diagnostic, this signature may have utility in rapid screening for emerging infections, avoidance of inappropriate antibacterial therapy, and more rapid implementation of appropriate therapeutic and public health strategies. PMID: 28238698 [PubMed - as supplied by publisher]

Related Articles Linking sources to early effects by profiling urine metabolome of residents living near oil refineries and coal-fired power plants. Environ Int. 2017 Feb 23;: Authors: Chen CS, Yuan TH, Shie RH, Wu KY, Chan CC Abstract BACKGROUND: This study aims at identifying metabolic changes linking external exposure to industrial air toxics with oxidative stress biomarkers. METHODS: We classified 252 study subjects as 111 high vs. 141 low exposure subjects by the distance from their homes to the two main emission sources, oil refineries and coal-fired power plants. We estimated individual's external exposure to heavy metals and polycyclic aromatic hydrocarbons (PAHs) by dispersion and kriging models, respectively. We measured urinary levels of heavy metals and 1-hydroxypyrene (1-OHP) as biomarkers of internal exposure, and 8-OHdG, HNE-MA, 8-isoPGF2α, and 8-NO2Gua as biomarkers of early health effects. We used two-dimensional gas chromatography time-of-flight mass spectrometry to identify urine metabolomics. We applied "meet-in-the-middle" approach to identify potential metabolites as putative intermediate biomarkers linking multiple air toxics exposures to oxidative stress with plausible exposures-related pathways. RESULTS: High exposure subjects showed elevated ambient concentrations of vanadium and PAHs, increased urine concentrations of 1-OHP, vanadium, nickel, copper, arsenic, strontium, cadmium, mercury, and thallium, and higher urine concentrations of all four urine oxidative stress biomarkers compared to low exposure subjects. We identified a profile of putative intermediate biomarkers that were associated with both exposures and oxidative stress biomarkers in participants. Urine metabolomics identified age-dependent biological pathways, including tryptophan metabolism and phenylalanine metabolism in children subjects (aged 9-11), and glycine, serine, and threonine metabolism in elderly subjects (aged>55), that could associate multiple exposures with oxidative stress. CONCLUSION: By profiling urine biomarkers and metabolomics in children and elderly residents living near a petrochemical complex, we can link their internal exposure to oxidative stress biomarkers through biological pathways associated with common complex chronic diseases and allergic respiratory diseases. The internal exposure may possibly be traced to multiple air toxics emitted from specific sources of oil refineries and coal-fired power plants. PMID: 28238459 [PubMed - as supplied by publisher]