PubMed

Related Articles Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review. Oncotarget. 2017 Mar 30;: Authors: Zhang F, Zhang Y, Zhao W, Deng K, Wang Z, Yang C, Ma L, Openkova MS, Hou Y, Li K Abstract Colorectal cancer (CRC) remains an incurable disease. There are no effective noninvasive techniques that have achieved colorectal cancer (CRC) diagnosis, prognosis, survival and recurrence in clinic. To investigate colorectal cancer metabolism, we perform an electronic literature search, from 1998 to January 2016, for studies evaluating the metabolomic profile of patients with CRC regarding the diagnosis, recurrence, prognosis/survival, and systematically review the twenty-three literatures included. QUADOMICS tool was used to assess the quality of them. We highlighted the metabolism perturbations based on metabolites and pathway. Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in CRC. Altered metabolites were also related to prognosis, survival and recurrence of CRC. This review could represent the most comprehensive information and summary about CRC metabolism to date. It certificates that metabolomics had great potential on both discovering clinical biomarkers and elucidating previously unknown mechanisms of CRC pathogenesis. PMID: 28389626 [PubMed - as supplied by publisher]

Related Articles Microbial Metabolites in Health and Disease: Navigating the Unknown in Search of Function. J Biol Chem. 2017 Apr 07;: Authors: Martinez KB, Leone VA, Chang EB Abstract The gut microbiota has been implicated in the development of a number of chronic gastrointestinal and systemic diseases. These include inflammatory bowel diseases, irritable bowel syndrome, metabolic (i.e. obesity, non-alcoholic fatty liver disease, diabetes), and neurological diseases. The advanced understanding of host-microbe interactions has largely been due to new technologies such as 16S rRNA sequencing to identify previously unknown microbial communities and more importantly their functional characteristics through metagenomic sequencing, and other multi-omic technologies such as metatranscriptomics, metaproteomics, and metabolomics. Given the vast array of newly acquired knowledge in the field and technological advances, it is expected that mechanisms underlying several disease states involving the interactions between microbes, their metabolites, and the host will be discovered. The identification of these mechanisms will allow for the development of more precise therapies to prevent or manage chronic disease. This review discusses the functional characterization of the microbiome, highlighting the advances in identifying bioactive microbial metabolites that have been directly linked to gastrointestinal and peripheral diseases. PMID: 28389566 [PubMed - as supplied by publisher]

Related Articles Introduction to the Thematic Minireview Series: Host-Microbiome Metabolic Interplay. J Biol Chem. 2017 Apr 07;: Authors: Banerjee R Abstract Long before the recent thrust of scientific research on the microbiome, the importance of its interface with the host was being acknowledged by practices such as probiotic supplementation e.g., after a course of antibiotics, which has the unwanted side effect of depleting commensal bacteria. The shared metabolite capital between the host and the microbiome is extensive and tightly controlled. However, despite the influence of microbial-derived metabolites on many aspects of host physiology, behavior and pathology, our understanding of this metabolic interface is still in its infancy and its therapeutic targeting is largely untapped. In this thematic minireview series, JBC presents six exciting articles discussing a range of approaches for identifying microbial natural products, and elucidating their biosynthetic pathways and their physiological effects, which could potentially be leveraged for developing new therapeutics. PMID: 28389560 [PubMed - as supplied by publisher]

Related Articles Targeting of Microbe-Derived Metabolites to Improve Human Health: The Next Frontier for Drug Discovery. J Biol Chem. 2017 Apr 07;: Authors: Brown JM, Hazen SL Abstract Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) has been causally linked to the development of cardiovascular diseases. Recent studies reveal drugging this pathway can inhibit atherosclerosis development in mice. Building on this example, we discuss challenges and untapped potential of targeting bacterial enzymology for improvements in human health. PMID: 28389555 [PubMed - as supplied by publisher]

Related Articles Robust identification of metabolic control for microbial l-methionine production following an easy-to-use puristic approach. Metab Eng. 2017 Apr 04;: Authors: Teleki A, Rahnert M, Bungart O, Gann B, Ochrombel I, Takors R Abstract The identification of promising metabolic engineering targets is a key issue in metabolic control analysis (MCA). Conventional approaches make intensive use of model-based studies, such as exploiting post-pulse metabolic dynamics after proper perturbation of the microbial system. Here, we present an easy-to-use, purely data-driven approach, defining pool efflux capacities (PEC) for identifying reactions that exert the highest flux control in linear pathways. Comparisons with linlog-based MCA and data-driven substrate elasticities (DDSE) showed that similar key control steps were identified using PEC. Using the example of l-methionine production with recombinant Escherichia coli, PEC consistently and robustly identified main flux controls using perturbation data after a non-labeled (12)C-l-serine stimulus. Furthermore, the application of full-labeled (13)C-l-serine stimuli yielded additional insights into stimulus propagation to l-methionine. PEC analysis performed on the (13)C data set revealed the same targets as the (12)C data set. Notably, the typical drawback of metabolome analysis, namely, the omnipresent leakage of metabolites, was excluded using the (13)C PEC approach. PMID: 28389396 [PubMed - as supplied by publisher]

Related Articles Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease. Cell Stem Cell. 2017 Apr 06;20(4):547-557.e7 Authors: Warren CR, O'Sullivan JF, Friesen M, Becker CE, Zhang X, Liu P, Wakabayashi Y, Morningstar JE, Shi X, Choi J, Xia F, Peters DT, Florido MH, Tsankov AM, Duberow E, Comisar L, Shay J, Jiang X, Meissner A, Musunuru K, Kathiresan S, Daheron L, Zhu J, Gerszten RE, Deo RC, Vasan RS, O'Donnell CJ, Cowan CA Abstract Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants. PMID: 28388431 [PubMed - in process]

Related Articles Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase. Cell. 2017 Apr 06;169(2):258-272.e17 Authors: Cantor JR, Abu-Remaileh M, Kanarek N, Freinkman E, Gao X, Louissaint A, Lewis CA, Sabatini DM Abstract A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility. PMID: 28388410 [PubMed - in process]

Related Articles Improved Quantum Chemical NMR Chemical Shift Prediction of Metabolites in Aqueous Solution Toward the Validation of Unknowns. J Phys Chem A. 2017 Apr 07;: Authors: Hoffmann F, Li DW, Sebastiani D, Bruschweiler R Abstract A quantum-chemistry based protocol, termed MOSS-DFT, is presented for the prediction of 13C and 1H NMR chemical shifts of a wide range of organic molecules in aqueous solution, including metabolites. Molecular motif-specific linear scaling parameters are reported for five different density functional theory (DFT) methods (B97-2/pcS-1, B97-2/pcS-2, B97-2/pcS-3, B3LYP/pcS-2 and BLYP/pcS-2), which were applied to a large set of 176 metabolite molecules. The chemical shift root-mean-square deviations (RMSD) for the best method, B97-2/pcS-3, are 1.93 ppm and 0.154 ppm for 13C and 1H chemical shifts, respectively. Excellent results have been obtained for chemical shifts of methyl and aromatic 13C and 1H that are not directly bonded to a heteroatom (O, N, S, or P) with RMSD values of 1.15/0.079 ppm and 1.31/0.118 ppm, respectively. This study not only demonstrates how NMR chemical shift predictions can be improved over the commonly used global linear scaling approach, but also allows for motif-specific error estimates, which are useful for an improved chemical shift-based verification of metabolite candidates of metabolomics samples containing unknown components. PMID: 28388058 [PubMed - as supplied by publisher]

Related Articles Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases. Int J Mol Sci. 2017 Apr 07;18(4): Authors: Dupont AC, Largeau B, Santiago Ribeiro MJ, Guilloteau D, Tronel C, Arlicot N Abstract In vivo exploration of activated microglia in neurodegenerative diseases is achievable by Positron Emission Tomography (PET) imaging, using dedicated radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO). In this review, we emphasized the major advances made over the last 20 years, thanks to TSPO PET imaging, to define the pathophysiological implication of microglia activation and neuroinflammation in neurodegenerative diseases, including Parkinson's disease, Huntington's disease, dementia, amyotrophic lateral sclerosis, multiple sclerosis, and also in psychiatric disorders. The extent and upregulation of TSPO as a molecular biomarker of activated microglia in the human brain is now widely documented in these pathologies, but its significance, and especially its protective or deleterious action regarding the disease's stage, remains under debate. Thus, we exposed new and plausible suggestions to enhance the contribution of TSPO PET imaging for biomedical research by exploring microglia's role and interactions with other cells in brain parenchyma. Multiplex approaches, associating TSPO PET radiopharmaceuticals with other biomarkers (PET imaging of cellular metabolism, neurotransmission or abnormal protein aggregates, but also other imaging modalities, and peripheral cytokine levels measurement and/or metabolomics analysis) was considered. Finally, the actual clinical impact of TSPO PET imaging as a routine biomarker of neuroinflammation was put into perspective regarding the current development of diagnostic and therapeutic strategies for neurodegenerative diseases. PMID: 28387722 [PubMed - in process]

Related Articles Gene-Diet Interaction and Precision Nutrition in Obesity. Int J Mol Sci. 2017 Apr 07;18(4): Authors: Heianza Y, Qi L Abstract The rapid rise of obesity during the past decades has coincided with a profound shift of our living environment, including unhealthy dietary patterns, a sedentary lifestyle, and physical inactivity. Genetic predisposition to obesity may have interacted with such an obesogenic environment in determining the obesity epidemic. Growing studies have found that changes in adiposity and metabolic response to low-calorie weight loss diets might be modified by genetic variants related to obesity, metabolic status and preference to nutrients. This review summarized data from recent studies of gene-diet interactions, and discussed integration of research of metabolomics and gut microbiome, as well as potential application of the findings in precision nutrition. PMID: 28387720 [PubMed - in process]

Related Articles Elucidating dynamic metabolic physiology through network integration of quantitative time-course metabolomics. Sci Rep. 2017 Apr 07;7:46249 Authors: Bordbar A, Yurkovich JT, Paglia G, Rolfsson O, Sigurjónsson ÓE, Palsson BO Abstract The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time-course absolute quantitative metabolomics. This approach, termed "unsteady-state flux balance analysis" (uFBA), is applied to four cellular systems: three dynamic and one steady-state as a negative control. uFBA and FBA predictions are contrasted, and uFBA is found to be more accurate in predicting dynamic metabolic flux states for red blood cells, platelets, and Saccharomyces cerevisiae. Notably, only uFBA predicts that stored red blood cells metabolize TCA intermediates to regenerate important cofactors, such as ATP, NADH, and NADPH. These pathway usage predictions were subsequently validated through (13)C isotopic labeling and metabolic flux analysis in stored red blood cells. Utilizing time-course metabolomics data, uFBA provides an accurate method to predict metabolic physiology at the cellular scale for dynamic systems. PMID: 28387366 [PubMed - in process]

Related Articles Metabolic Response of Visceral White Adipose Tissue of Obese Mice Exposed for 5 Days to Human Room Temperature Compared to Mouse Thermoneutrality. Front Physiol. 2017;8:179 Authors: van der Stelt I, Hoevenaars F, Široká J, de Ronde L, Friedecký D, Keijer J, van Schothorst E Abstract Housing of laboratory mice at room temperature (22°C) might be considered a constant cold stress, which induces a thermogenic program in brown adipose tissue (BAT). However, the early adaptive response of white adipose tissue (WAT), the fat storage organ of the body, to a change from thermoneutrality to room temperature is not known. This was investigated here for various WAT depots, focusing on epididymal WAT (eWAT), widely used as reference depot. Male adult diet-induced obese (DIO) C57BL/6JOlaHsd mice housed at thermoneutrality (29°C), were for 5 days either switched to room temperature (22°C) or remained at thermoneutrality. Energy metabolism was continuously measured using indirect calorimetry. At the end of the study, serum metabolomics and WAT transcriptomics were performed. We confirmed activation of the thermogenic program in 22°C housed mice. Body weight and total fat mass were reduced. Whole body energy expenditure (EE) was increased, with a higher fatty acid to carbohydrate oxidation ratio and increased serum acylcarnitine levels, while energy intake was not significantly different between the two groups. Transcriptome analysis of eWAT identified tissue remodeling and inflammation as the most affected processes. Expression of pro-inflammatory M1 macrophage-related genes, and M1 over M2 macrophage ratio were decreased, which might be linked to an increased insulin sensitivity. Markers of thermogenesis were not altered in eWAT. Decreased expression of tryptophan hydroxylase 2 (Tph2) and cholecystokinin (Cck) might represent altered neuroendocrine signaling. eWAT itself does not show increased fatty acid oxidation. The three measured WATs, epididymal, mesenteric, and retroperitoneal, showed mainly similar responses; reduced inflammation (s100a8), decreased carbohydrate oxidation, and no or small differences in fatty acid oxidation. However, Ucp1 was only expressed and increased in rWAT in 22°C housed mice. Cck expression was decreased in the three WATs, significantly in eWAT and rWAT, in contrast to Tph2, which was decreased in eWAT while not expressed in mWAT and rWAT. Our data show that tissue remodeling, inflammation and neuroendocrine signaling are early responses in WAT to a moderate decrease in environmental temperature. PMID: 28386236 [PubMed - in process]

Related Articles Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature. 2017 01 05;541(7635):81-86 Authors: Wahl S, Drong A, Lehne B, Loh M, Scott WR, Kunze S, Tsai PC, Ried JS, Zhang W, Yang Y, Tan S, Fiorito G, Franke L, Guarrera S, Kasela S, Kriebel J, Richmond RC, Adamo M, Afzal U, Ala-Korpela M, Albetti B, Ammerpohl O, Apperley JF, Beekman M, Bertazzi PA, Black SL, Blancher C, Bonder MJ, Brosch M, Carstensen-Kirberg M, de Craen AJ, de Lusignan S, Dehghan A, Elkalaawy M, Fischer K, Franco OH, Gaunt TR, Hampe J, Hashemi M, Isaacs A, Jenkinson A, Jha S, Kato N, Krogh V, Laffan M, Meisinger C, Meitinger T, Mok ZY, Motta V, Ng HK, Nikolakopoulou Z, Nteliopoulos G, Panico S, Pervjakova N, Prokisch H, Rathmann W, Roden M, Rota F, Rozario MA, Sandling JK, Schafmayer C, Schramm K, Siebert R, Slagboom PE, Soininen P, Stolk L, Strauch K, Tai ES, Tarantini L, Thorand B, Tigchelaar EF, Tumino R, Uitterlinden AG, van Duijn C, van Meurs JB, Vineis P, Wickremasinghe AR, Wijmenga C, Yang TP, Yuan W, Zhernakova A, Batterham RL, Smith GD, Deloukas P, Heijmans BT, Herder C, Hofman A, Lindgren CM, Milani L, van der Harst P, Peters A, Illig T, Relton CL, Waldenberger M, Järvelin MR, Bollati V, Soong R, Spector TD, Scott J, McCarthy MI, Elliott P, Bell JT, Matullo G, Gieger C, Kooner JS, Grallert H, Chambers JC Abstract Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10(-7), range P = 9.2 × 10(-8) to 6.0 × 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10(-6), range P = 5.5 × 10(-6) to 6.1 × 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity. PMID: 28002404 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic profiling of breast tumors using ductal fluid. Int J Oncol. 2016 Dec;49(6):2245-2254 Authors: Matos Do Canto L, Marian C, Varghese RS, Ahn J, Da Cunha PA, Willey S, Sidawy M, Rone JD, Cheema AK, Luta G, Nezami Ranjbar MR, Ressom HW, Haddad BR Abstract Identification of new biomarkers for breast cancer remains critical in order to enhance early detection of the disease and improve its prognosis. Towards this end, we performed an untargeted metabolomic analysis of breast ductal fluid using an ultra-performance liquid chromatography coupled with a quadrupole time-of-light (UPLC-QTOF) mass spectrometer. We investigated the metabolomic profiles of breast tumors using ductal fluid samples collected by ductal lavage (DL). We studied fluid from both the affected breasts and the unaffected contralateral breasts (as controls) from 43 women with confirmed unilateral breast cancer. Using this approach, we identified 1560 ions in the positive mode and 538 ions in the negative mode after preprocessing of the UPLC‑QTOF data. Paired t-tests applied on these data matrices identified 209 ions (positive and negative modes combined) with significant change in intensity level between affected and unaffected control breasts (adjusted p-values <0.05). Among these, 83 ions (39.7%) showed a fold change (FC) >1.2 and 66 ions (31.6%) were identified with putative compound names. The metabolites that we identified included endogenous metabolites such as amino acid derivatives (N-Acetyl-DL-tryptophan) or products of lipid metabolism such as N-linoleoyl taurine, trans-2-dodecenoylcarnitine, lysophosphatidylcholine LysoPC(18:2(9Z,12Z)), glycerophospholipids PG(18:0/0:0), and phosphatidylserine PS(20:4(5Z,8Z,11Z,14Z). Generalized LASSO regression further selected 21 metabolites when race, menopausal status, smoking, grade and TNM stage were adjusted for. A predictive conditional logistic regression model, using the LASSO selected 21 ions, provided diagnostic accuracy with the area under the curve of 0.956 (sensitivity/specificity of 0.907/0.884). This is the first study that shows the feasibility of conducting a comprehensive metabolomic profiling of breast tumors using breast ductal fluid to detect changes in the cellular microenvironment of the tumors and shows the potential for this approach to be used to improve detection of breast cancer. PMID: 27748798 [PubMed - indexed for MEDLINE]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/04/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/04/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development. Obes Facts. 2017 Apr 05;10(2):85-100 Authors: Hellmuth C, Uhl O, Standl M, Demmelmair H, Heinrich J, Koletzko B, Thiering E Abstract BACKGROUND/AIMS: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. METHODS: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. RESULTS: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. CONCLUSION: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome. PMID: 28376503 [PubMed - as supplied by publisher]

Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin-proteasome systems. Transl Psychiatry. 2017 Apr 04;7(4):e1078 Authors: Park DI, Dournes C, Sillaber I, Ising M, Asara JM, Webhofer C, Filiou MD, Müller MB, Turck CW Abstract The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels. In addition, we found that chronic paroxetine treatment altered the levels of proteins associated with the ubiquitin-proteasome system (UPS). The soluble guanylate cyclase-β1, proteasome subunit α type-2 and ubiquitination levels were also affected in peripheral blood mononuclear cells from antidepressant responder and non-responder patients suffering from major depressive disorder. We submit that the glutamatergic system and UPS have a crucial role in the antidepressant treatment response in both mice and humans. PMID: 28375208 [PubMed - in process]

Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination. Int J Mol Sci. 2017 Apr 04;18(4): Authors: Itoi T, Sugimoto M, Umeda J, Sofuni A, Tsuchiya T, Tsuji S, Tanaka R, Tonozuka R, Honjo M, Moriyasu F, Kasuya K, Nagakawa Y, Abe Y, Takano K, Kawachi S, Shimazu M, Soga T, Tomita M, Sunamura M Abstract This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases. PMID: 28375170 [PubMed - in process]

Sialylation is dispensable for early murine embryonic development in vitro. Chembiochem. 2017 Apr 04;: Authors: Abeln M, Borst K, Cajic S, Thiesler H, Kats E, Albers I, Kuhn M, Kaever V, Rapp E, Münster-Kühnel A, Weinhold B Abstract The negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. To elucidate the impact of sialylation on differentiation processes in the absence of maternal effects, we generated mouse embryonic stem cell (mESC) lines that lack CMP-Sia synthetase (CMAS) and thereby the capacity of activating Sia to CMP-Sia. Loss of CMAS activity resulted in an asialo cell surface, accompanied by an increase in glycoconjugates with terminal galactosyl and oligo-LacNAc residues as well as intracellular accumulation of free Sia. Remarkably, observed changes did neither impact intracellular metabolites nor the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas-/- mESC for undirected differentiation into embryoid bodies, germ layer formation and even generation of beating cardiomyocytes provides first and doubtless evidence that pluripotency and differentiation of mESC in vitro can proceed in the absence of (poly)sialoglycans. PMID: 28374933 [PubMed - as supplied by publisher]