PubMed

[The action mechanisms of Morus alba leaves extract for the treatment of diabetes based on plasma metabolomics]. Yao Xue Xue Bao. 2015 Jul;50(7):830-5 Authors: Ji T, Zhang LL, Huang XC, Su SL, Ouyang Z, Zhu ZH, Guo S, Shang EX, Qian DW, Duan JA Abstract In order to evaluate the effect and mechanism of the mulberry leaf alkaloid, flavones, and polysaccharide intervention on diabetes, the overall metabolite profiling characteristics for the plasma of diabetic mouse was performed by using an ultra-performance liquid chromatography/electrospray-tandem mass spectrometry (UPLC-ESI-MS). The 8 potential biomarkers were found in diabetic mice plasma based on the data of MS/MS characteristics obtained from the UPLC-OrbitrapMS analysis, which mainly involved in sphingolipids, amino acid metabolic pathway. The principal component analysis showed that the normal group and model group were obviously distinguished and implied that metabolic disturbance was happened in diabetic mice plasma. The extracts of mulberry leaf flavonoids, polysaccharide, alkaloid had exhibited the effects of callback function for diabetic mice through regulating the amino acid metabolism and sphingolipid metabolism. PMID: 26552143 [PubMed - in process]

Related Articles Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors. Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4410-7 Authors: Daemen A, Peterson D, Sahu N, McCord R, Du X, Liu B, Kowanetz K, Hong R, Moffat J, Gao M, Boudreau A, Mroue R, Corson L, O'Brien T, Qing J, Sampath D, Merchant M, Yauch R, Manning G, Settleman J, Hatzivassiliou G, Evangelista M Abstract Although targeting cancer metabolism is a promising therapeutic strategy, clinical success will depend on an accurate diagnostic identification of tumor subtypes with specific metabolic requirements. Through broad metabolite profiling, we successfully identified three highly distinct metabolic subtypes in pancreatic ductal adenocarcinoma (PDAC). One subtype was defined by reduced proliferative capacity, whereas the other two subtypes (glycolytic and lipogenic) showed distinct metabolite levels associated with glycolysis, lipogenesis, and redox pathways, confirmed at the transcriptional level. The glycolytic and lipogenic subtypes showed striking differences in glucose and glutamine utilization, as well as mitochondrial function, and corresponded to differences in cell sensitivity to inhibitors of glycolysis, glutamine metabolism, lipid synthesis, and redox balance. In PDAC clinical samples, the lipogenic subtype associated with the epithelial (classical) subtype, whereas the glycolytic subtype strongly associated with the mesenchymal (QM-PDA) subtype, suggesting functional relevance in disease progression. Pharmacogenomic screening of an additional ∼ 200 non-PDAC cell lines validated the association between mesenchymal status and metabolic drug response in other tumor indications. Our findings highlight the utility of broad metabolite profiling to predict sensitivity of tumors to a variety of metabolic inhibitors. PMID: 26216984 [PubMed - indexed for MEDLINE]

Related Articles A recycling pathway for cyanogenic glycosides evidenced by the comparative metabolic profiling in three cyanogenic plant species. Biochem J. 2015 Aug 1;469(3):375-89 Authors: Pičmanová M, Neilson EH, Motawia MS, Olsen CE, Agerbirk N, Gray CJ, Flitsch S, Meier S, Silvestro D, Jørgensen K, Sánchez-Pérez R, Møller BL, Bjarnholt N Abstract Cyanogenic glycosides are phytoanticipins involved in plant defence against herbivores by virtue of their ability to release toxic hydrogen cyanide (HCN) upon tissue disruption. In addition, endogenous turnover of cyanogenic glycosides without the liberation of HCN may offer plants an important source of reduced nitrogen at specific developmental stages. To investigate the presence of putative turnover products of cyanogenic glycosides, comparative metabolic profiling using LC-MS/MS and high resolution MS (HR-MS) complemented by ion-mobility MS was carried out in three cyanogenic plant species: cassava, almond and sorghum. In total, the endogenous formation of 36 different chemical structures related to the cyanogenic glucosides linamarin, lotaustralin, prunasin, amygdalin and dhurrin was discovered, including di- and tri-glycosides derived from these compounds. The relative abundance of the compounds was assessed in different tissues and developmental stages. Based on results common to the three phylogenetically unrelated species, a potential recycling endogenous turnover pathway for cyanogenic glycosides is described in which reduced nitrogen and carbon are recovered for primary metabolism without the liberation of free HCN. Glycosides of amides, carboxylic acids and 'anitriles' derived from cyanogenic glycosides appear as common intermediates in this pathway and may also have individual functions in the plant. The recycling of cyanogenic glycosides and the biological significance of the presence of the turnover products in cyanogenic plants open entirely new insights into the multiplicity of biological roles cyanogenic glycosides may play in plants. PMID: 26205491 [PubMed - indexed for MEDLINE]

Related Articles Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma. Mol Nutr Food Res. 2014 Nov;58(11):2111-21 Authors: Smit S, Szymańska E, Kunz I, Gomez Roldan V, van Tilborg MW, Weber P, Prudence K, van der Kloet FM, van Duynhoven JP, Smilde AK, de Vos RC, Bendik I Abstract SCOPE: Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasing many different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites. METHODS AND RESULTS: In a randomized cross-over trial, 12 healthy young volunteers were administered a single dose of 30 mg genistein provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS platform detected and quantified in human plasma: free genistein, seven of its phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel metabolite, genistein-4'-glucuronide-7-sulfate (G-4'G-7S) was identified. Nutrikinetic analysis using population-based modeling revealed the order of appearance of five genistein phase II metabolites in plasma: (1) genistein-4',7-diglucuronide, (2) genistein-7-sulfate, (3) genistein-4'-sulfate-7-glucuronide, (4) genistein-4'-glucuronide, and (5) genistein-7-glucuronide, independent of the food matrix. CONCLUSION: The conjugated genistein metabolites appear in a distinct order in human plasma. The specific early appearance of G-4',7-diG suggests a multistep formation process for the mono and hetero genistein conjugates, involving one or two deglucuronidation steps. PMID: 25045152 [PubMed - indexed for MEDLINE]

16 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 2015/11/10PubMed comprises more than 24 million 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.

Regularized MANOVA (rMANOVA) in untargeted metabolomics. Anal Chim Acta. 2015 Oct 29;899:1-12 Authors: Engel J, Blanchet L, Bloemen B, van den Heuvel LP, Engelke UH, Wevers RA, Buydens LM Abstract Many advanced metabolomics experiments currently lead to data where a large number of response variables were measured while one or several factors were changed. Often the number of response variables vastly exceeds the sample size and well-established techniques such as multivariate analysis of variance (MANOVA) cannot be used to analyze the data. ANOVA simultaneous component analysis (ASCA) is an alternative to MANOVA for analysis of metabolomics data from an experimental design. In this paper, we show that ASCA assumes that none of the metabolites are correlated and that they all have the same variance. Because of these assumptions, ASCA may relate the wrong variables to a factor. This reduces the power of the method and hampers interpretation. We propose an improved model that is essentially a weighted average of the ASCA and MANOVA models. The optimal weight is determined in a data-driven fashion. Compared to ASCA, this method assumes that variables can correlate, leading to a more realistic view of the data. Compared to MANOVA, the model is also applicable when the number of samples is (much) smaller than the number of variables. These advantages are demonstrated by means of simulated and real data examples. The source code of the method is available from the first author upon request, and at the following github repository: https://github.com/JasperE/regularized-MANOVA. PMID: 26547490 [PubMed - as supplied by publisher]

Toxic effects of male Perna viridisgonad exposed to BaP, DDT and their mixture: A metabolomic and proteomic study of the underlying mechanism. Toxicol Lett. 2015 Nov 4; Authors: Song Q, Zheng P, Qiu L, Jiang X, Zhao H, Zhou H, Han Q, Diao X Abstract Benzo(a)pyrene and dichlorodiphenyltrichloroethane are typical persistent organic pollutants, and also the widespread environmental estrogens with known toxicity towards green mussels Perna viridis. In this study, the toxicological effects of BaP and DDT and their mixture were assessed in green mussel gonads using proteomic and metabolomic approaches. Metabolomics by NMR spectroscopy revealed that BaP didn't show obvious metabolite changes in the gonad of male green mussel. DDT mainly caused some disturbance of osmotic regulation and energy metabolism by changing BCAAs, alanine, threonine, arginine, etc., unknown metabolite (3.53ppm), glycine, homarine and ATP at different levels. However, the mixture of BaP and DDT mainly caused some disturbance in osmotic regulation and energy metabolism by differentially altering branched chain amino acids, glutamate, alanine, arginine, unknown metabolite (3.53ppm), glycine, 4-aminobutyrate, dimethylglycine, homarine and ATP. The results suggest that DDT alone may cause most of metabolites changes in the mixture exposed mussel gonad, and the results also show that the male Perna viridis gonad was more sensitive to DDT than BaP exposures. Proteomic study showed that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced signal transduction, oxidative stress, spermatogenesis, etc. in the male green mussel gonad; whereas DDT exposure altered proteins that were associated with signal transduction, oxidative stress, cytoskeleton and cell structure, cellular organization, energy metabolism, etc. However, the mixture of BaP and DDT affected proteins related to cytoskeleton and cell structure, oxidative stress, cellular organization, etc. This research demonstrated that metabolomic and proteomic approaches could better elucidate the underlying mechanism of environmental pollutants gonad toxicity. PMID: 26546779 [PubMed - as supplied by publisher]

Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis. J Biol Chem. 2015 Nov 6; Authors: Poisson LM, Suhail H, Singh J, Datta I, Denic A, Labuzek K, Hoda MN, Shankar A, Kumar A, Cerghet M, Elias S, Mohney RP, Rodriguez M, Rattan R, Mangalam AK, Giri S Abstract We performed untargeted metabolomics of plasma from B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation and membrane stability were observed to be significantly altered between EAE and healthy control (p < 0.05, false discover rate [< 0.10]. Bioinformatics analysis revealed 6 metabolic pathways being impacted and altered in EAE including alpha linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including omega 3 and omega 6 fatty acids, are commonly decreased in mouse models and in multiple sclerosis patients. Daily oral administration of resolvin D1, a downstream metabolite of omega 3, decreased disease progression by suppressing autoreactive T cells and inducing a M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of a metabolomic approach to identify endogenous metabolite(s) possessing drug-like properties, which is tested for therapy in preclinical mouse models. PMID: 26546682 [PubMed - as supplied by publisher]

1H NMR metabolic profiling of cod (Gadus morhua) larvae: potential effects of temperature and diet composition during early developmental stages. Biol Open. 2015 Nov 6; Authors: Chauton MS, Galloway TF, Kjørsvik E, Størseth TR, Puvanendran V, van der Meeren T, Karlsen Ø, Rønnestad I, Hamre K Abstract Marine aquaculture offers a great source of protein for the increasing human population, and farming of, for example, Atlantic salmon is a global industry. Atlantic cod farming however, is an example of a promising industry where the potential is not yet realized. Research has revealed that a major bottleneck to successful farming of cod is poor quality of the larvae and juveniles. A large research program was designed to increase our understanding of how environmental factors such as temperature and nutrition affects cod larvae development. Data on larvae growth and development were used together with nuclear magnetic resonance. The NMR data indicated that the temperature influenced the metabolome of the larvae; differences were related to osmolytes such as betaine/TMAO, the amino acid taurine, and creatine and lactate which reflect muscle activity. The larvae were fed Artemia from stage 2, and this was probably reflected in a high taurine content of older larvae. Larvae fed with copepods in the nutrition experiment also displayed a high taurine content, together with higher creatine and betaine/TMAO content. Data on the cod larvae metabolome should be coupled to data on gene expression, in order to identify events which are regulated on the genetic level versus regulation resulting from temperature or nutrition during development, to fully understand how the environment affects larval development. PMID: 26545964 [PubMed - as supplied by publisher]

Integration of metabolomics and transcriptomics reveals major metabolic pathways and potential biomarker involved in prostate cancer. Mol Cell Proteomics. 2015 Nov 6; Authors: Ren S, Shao Y, Zhao X, Hong CS, Wang F, Lu X, Li J, Ye G, Zhuang Z, Xu C, Xu G, Sun Y Abstract Prostate cancer is a highly prevalent tumor affecting millions of men world-wide, but poor understanding of its pathogenesis has limited effective clinical management of patients. In addition to transcriptional profiling or transcriptomics, metabolomics is being increasingly utilized to discover key molecular changes underlying tumorigenesis. In this study, we integrated transcriptomics and metabolomics to analyze 25 paired human prostate cancer tissues and adjacent noncancerous tissues, followed by further validation of our findings in an additional cohort of 51 prostate cancer patients and 16 benign prostatic hyperplasia patients. We found several altered pathways aberrantly expressed at both metabolic and transcriptional levels, including cysteine and methionine metabolism, nicotinamide adenine dinucleotide metabolism, and hexosamine biosynthesis. Additionally, the metabolite sphingosine demonstrated high specificity and sensitivity for distinguishing prostate cancer from benign prostatic hyperplasia, particularly for patients with low prostate specific antigen level (0-10 ng/mL). We also found impaired sphingosine-1-phosphate receptor 2 signaling, downstream of sphingosine, representing a loss of tumor suppressor gene and a potential key oncogenic pathway for therapeutic targeting. By integrating metabolomics and transcriptomics, we have provided both a broad picture of the molecular perturbations underlying prostate cancer and a preliminary study of a novel metabolic signature, which may help to discriminate prostate cancer from normal tissue and benign prostatic hyperplasia. PMID: 26545398 [PubMed - as supplied by publisher]

Pioneering ambient mass spectrometry imaging in psychiatry: Potential for new insights into schizophrenia. Schizophr Res. 2015 Nov 3; Authors: Vendramini PH, Gattaz WF, Schmitt A, Falkai P, Eberlin MN, Martins-de-Souza D PMID: 26545296 [PubMed - as supplied by publisher]

Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice. Atherosclerosis. 2015 Oct 26;243(2):598-608 Authors: Rasmiena AA, Barlow CK, Stefanovic N, Huynh K, Tan R, Sharma A, Tull D, de Haan JB, Meikle PJ Abstract BACKGROUND AND AIM: We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. METHODS AND RESULTS: Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. CONCLUSION: Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. PMID: 26545014 [PubMed - as supplied by publisher]

High-throughput platforms for metabolomics. Curr Opin Chem Biol. 2015 Nov 3;30:7-13 Authors: de Raad M, Fischer CR, Northen TR Abstract Mass spectrometry has become a choice method for broad-spectrum metabolite analysis in both fundamental and applied research. This can range from comprehensive analysis achieved through time-consuming chromatography to the rapid analysis of a few target metabolites without chromatography. In this review article, we highlight current high-throughput MS-based platforms and their potential application in metabolomics. Although current MS platforms can reach throughputs up to 0.5seconds per sample, the metabolite coverage of these platforms are low compared to low-throughput, separation-based MS methods. High-throughput comes at a cost, as it's a trade-off between sample throughput and metabolite coverage. As we will discuss, promising emerging technologies, including microfluidics and miniaturization of separation techniques, have the potential to achieve both rapid and more comprehensive metabolite analysis. PMID: 26544850 [PubMed - as supplied by publisher]

Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study. PLoS One. 2015;10(11):e0142610 Authors: Alonso A, Yu B, Qureshi WT, Grams ME, Selvin E, Soliman EZ, Loehr LR, Chen LY, Agarwal SK, Alexander D, Boerwinkle E Abstract BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited. METHODS: We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987-1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates. RESULTS: During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12-1.32) for glycolithocholate sulfate and 1.22 (1.10-1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes. CONCLUSION: We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted. PMID: 26544570 [PubMed - as supplied by publisher]

Diabetes and cardiovascular disease: let's push forward with translational research. Cardiovasc Diagn Ther. 2015 Oct;5(5):407-11 Authors: Paneni F, Costantino S Abstract Albeit advances in therapy have reduced morbidity and mortality in patients with diabetes, cardiovascular (CV) risk is far to be eradicated. This is partially due to the fact that breakthrough therapies have yet to be approved to counteract the atherosclerotic burden in this setting. Therefore, it is very important to understand the molecular mechanisms underpinning diabetes-related CV complications. Growing evidence is supporting the concept that translational research is perhaps the best approach to unveil novel insights into disease etiology and its link with CV phenotypes. The recent employment of high throughput "omics" (i.e., metabolomics, transcriptomics, proteomics) is a clinically relevant approach which may provide insightful interpretations of diabetes-related biological signals. The possibility to analyse thousands or more molecules simultaneously has given "omics" the ability to generate enormous quantities of data which may somehow offer a precious "window on the disease". In the present article, we critically discuss the importance of translational research in diabetes, including potential difficulties which may arise in the implementation and development of promising technologies from the laboratory to the marketplace. PMID: 26543828 [PubMed]

Production of hyperpolarized (13)CO2 from [1-(13)C]pyruvate in perfused liver does reflect total anaplerosis but is not a reliable biomarker of glucose production. Metabolomics. 2015 Oct;11(5):1144-1156 Authors: Moreno KX, Moore CL, Burgess SC, Sherry AD, Malloy CR, Merritt ME Abstract In liver, (13)CO2 can be generated from [1-(13)C] pyruvate via pyruvate dehydrogenase or anaplerotic entry of pyruvate into the TCA cycle followed by decarboxylation at phosphoenolpyruvate carboxykinase (PEPCK), the malic enzyme, isocitrate dehydrogenase, or α-ketoglutarate dehydrogenase. The purpose of this study was to determine the relative importance of these pathways in production of hyperpolarized (HP) (13)CO2 after administration of hyper-polarized pyruvate in livers supplied with a fatty acid plus substrates for gluconeogenesis. Isolated mouse livers were perfused with a mixture of thermally-polarized (13)C-enriched pyruvate, lactate and octanoate in various combinations prior to exposure to HP pyruvate. Under all perfusion conditions, HP malate, aspartate and fumarate were detected within ~ 3 s showing that HP [1-(13)C]pyruvate is rapidly converted to [1-(13)C]oxaloacetate which can subsequently produce HP (13)CO2 via decarboxylation at PEPCK. Measurements using HP [2-(13)C]pyruvate allowed the exclusion of reactions related to TCA cycle turnover as sources of HP (13)CO2. Direct measures of O2 consumption, ketone production, and glucose production by the intact liver combined with (13)C isotopomer analyses of tissue extracts yielded a comprehensive profile of metabolic flux in perfused liver. Together, these data show that, even though the majority of HP (13)CO2 derived from HP [1-(13)C]pyruvate in livers exposed to fatty acids reflects decarboxylation of [4-(13)C]oxaloacetate (PEPCK) or [4-(13)C]malate (malic enzyme), the intensity of the HP (13)CO2 signal is not proportional to glucose production because the amount of pyruvate returned to the TCA cycle via PEPCK and pyruvate kinase is variable, depending upon available substrates. PMID: 26543443 [PubMed - as supplied by publisher]

Calcified nodules on fingers in a primary hyperoxaluria type 2. Lancet Diabetes Endocrinol. 2015 Nov 2; Authors: Yamanouchi M, Ubara Y, Takayama T, Kuhara T, Takaichi K PMID: 26542998 [PubMed - as supplied by publisher]

Lessons learned from metabolomics in cystic fibrosis. Mol Cell Pediatr. 2015 Dec;2(1):9 Authors: Muhlebach MS, Sha W Abstract Cystic fibrosis is a mono-genetic multi-system disease; however, respiratory manifestations cause the main morbidity and mortality where chronic bacterial infections lead to bronchiectasis and ultimately respiratory failure. Metabolomics allows a relatively complete snapshot of metabolic processes in a sample using different mass spectrometry methods. Sample types used for discovery of biomarkers or pathomechanisms in cystic fibrosis (CF) have included blood, respiratory secretions, and exhaled breath to date. Metabolomics has shown distinction of CF vs. non-CF for matrices of blood, exhaled breath, and respiratory epithelial cultures, each showing different pathways. Severity of lung disease has been addressed by studies in bronchoalveolar lavage and exhaled breath condensate showing separation by metabolites that the authors of each study related to inflammation; e.g., ethanol, acetone, purines. Lipidomics has been applied to blood and sputum samples showing associations with lung function and Pseudomonas aeruginosa infection status. Finally, studies of bacteria grown in vitro showed differences of bacterial metabolites to be associated with clinical parameters. Metabolomics, in the sense of global metabolomic profiling, is a powerful technique that has allowed discovery of pathways that had not previously been implicated in CF. These may include purines, mitochondrial pathways, and different aspects of glucose metabolism besides the known differences in lipid metabolism in CF. However, targeted studies to validate such potential metabolites and pathways of interest are necessary. Studies evaluating metabolites of bacterial origin are in their early stages. Thus further well-designed studies could be envisioned. PMID: 26542299 [PubMed]

Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015 Nov 5; Authors: Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP, Poirier-Colame V, Roux A, Becharef S, Formenti S, Golden E, Cording S, Eberl G, Schlitzer A, Ginhoux F, Mani S, Yamazaki T, Jacquelot N, Enot DP, Bérard M, Nigou J, Opolon P, Eggermont A, Woerther PL, Chachaty E, Chaput N, Robert C, Mateus C, Kroemer G, Raoult D, Boneca IG, Carbonnel F, Chamaillard M, Zitvogel L Abstract Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, or by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that anti-CTLA-4 treatment of melanoma patients favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade. PMID: 26541610 [PubMed - as supplied by publisher]

Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-α2. J Neuroimmune Pharmacol. 2015 Nov 5; Authors: Valeria R, Luisa S, Adele M, Stefania B, Fabio T, Nicoletta B, Carmine PM, Silvia A Abstract Interferon (IFN)-α2 is an extensively therapeutically used pro-inflammatory cytokine. Though its efficacy in controlling viral replication and tumor cells proliferation, administration of IFN-α2 is often associated with the development of central side effects. Magnetic resonance spectroscopy studies have demonstrated that IFN-α2 administration affects brain metabolism, however the exact nature of this effect is not completely known. We hypothesized that IFN-α2 can affect metabolic activity of human neuron-like SH-SY5Y cells which possess many characteristics of neurons and represent one of the most used models for studying mechanisms involved in neurotoxicity or neuroprotection. To test our hypothesis we have characterized the metabolic signature of live SH-SY5Y, and their conditioned media, after 24 and 72 h of exposure to vehicle or IFN-α2 (100 ng/ml) by using High Resolution-Magic Angle Spinning (HR-MAS) Nuclear Magnetic Resonance (NMR) spectroscopy. Our results revealed that 1) the use of HR-MAS NMR is ideally suitable for the characterization of the metabolic profile of live cells and their conditioned media without extraction procedures; and 2) a 72 h exposure to IFN-α2 increases the level of metabolites involved in maintaining energetic (including creatine and lactate) and osmotic (such as myo-inositol, scyllo-inositol, taurine and glycerophosphorylcholine) balances in neuron-like cells and of metabolic waste products (namely lactate, ethanol and acetate), glycine and glutamine in their growth media. These results may contribute to gain more knowledge about the IFN-α2 induced effect on the brain and support the interpretation of magnetic resonance spectroscopy studies performed in humans. PMID: 26541470 [PubMed - as supplied by publisher]