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34 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 2017/08/02PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 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 2017/08/01PubMed 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.

A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2017 Jul 29;: Authors: Shen CT, Zhang Y, Liu YM, Yin S, Zhang XY, Wei WJ, Sun ZK, Song HJ, Qiu ZL, Wang CR, Luo QY Abstract BACKGROUND: Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis as well as cell status like metabolism changes in distant metastatic tumors have not been clearly elucidated. OBJECTIVE: To identify serum metabolic signature of distant metastatic PTC. DESIGN, PATIENTS AND MEASUREMENTSIN: this study, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA)scores plots were used to analyze the data. RESULTS: PCA and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed 'alanine, aspartate and glutamate metabolism' and 'inositol phosphate metabolism' were the most relevant pathways. CONCLUSION: Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biologic behaviors of tumor cells including proliferation, invasion/migration, and immune escape. Diet/gut microbiota produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding to the distant metastasis of PTC as well as potential adjuvant therapy targets. This article is protected by copyright. All rights reserved. PMID: 28755525 [PubMed - as supplied by publisher]

Spectrum Evaluation-assisted Eicosanoid Metabolomics for Global Eicosanoid Profiling in Human Vascular Endothelial Cells. Clin Exp Pharmacol Physiol. 2017 Jul 29;: Authors: Bao Q, Liu Y, Song H, Yang N, Ai D, Zhu Y, Zhang X Abstract Eicosanoids are hundreds of metabolites derived from poly-unsaturated fatty acids (PUFAs), which regulate biological processes from multiple angles via a complex metabolic network. Targeted eicosanoid metabolomics is used to study the eicosanoid profile in biological samples but only for eicosanoids with available standards. To expand the coverage of eicosanoids detected, we identified the eicosanoids without available standards by estimation of the retention time and comparison of the MS/MS spectra with the reference ones which was collected in a database from literature. Scheduled multiple reaction monitoring- information dependent acquisition- enhanced product ion (sMRM-IDA-EPI) scan mode was applied in this method, which was called Spectrum Evaluation-assisted Eicosanoid Metabolomics (SEEM). By using this method, 243 eicosanoids (167 without standards) could be relatively quantified with precision over 90 percent. We applied the method to analyze the global profile of eicosanoids secreted by human umbilical vascular endothelial cells at the basal level and with n-3 PUFA treatment. 26 putative eicosanoids showed altered levels, despite no available standards. In general, n-3 PUFA treatment increased most of their own metabolites and decreased the epoxy-, hydroxyl- and keto- linoleic acid metabolites. The application of the SEEM method proved its potency of identification and quantification of eicosanoids without standards. This article is protected by copyright. All rights reserved. PMID: 28755503 [PubMed - as supplied by publisher]

Related Articles (1)H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation. Sci Rep. 2017 Jul 28;7(1):6820 Authors: Lin C, Wei Z, Cheng KK, Xu J, Shen G, She C, Zhong H, Chang X, Dong J Abstract Acupuncture is a traditional Chinese medicine therapy that has been found useful for treating various diseases. The treatments involve the insertion of fine needles at acupoints along specific meridians (meridian specificity). This study aims to investigate the metabolic basis of meridian specificity using proton nuclear magnetic resonance ((1)H NMR)-based metabolomics. Electro-acupuncture (EA) stimulations were performed at acupoints of either Stomach Meridian of Foot-Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male Sprague Dawley (SD) rats. (1)H-NMR spectra datasets of serum, urine, cortex, and stomach tissue extracts from the rats were analysed by multivariate statistical analysis to investigate metabolic perturbations due to EA treatments at different meridians. EA treatment on either the SMFY or GMFS acupoints induced significant variations in 31 metabolites, e.g., amino acids, organic acids, choline esters and glucose. Moreover, a few meridian-specific metabolic changes were found for EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant metabolic differences in response to EA stimulations on acupoints of SMFY and GMFS meridians. These results validate the hypothesis that meridian specificity in acupuncture is detectable in the metabolome and demonstrate the feasibility and effectiveness of a metabolomics approach in understanding the mechanism of acupuncture. PMID: 28754994 [PubMed - in process]

Related Articles Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis. Oncotarget. 2017 Jul 10;: Authors: Gong ZG, Zhao W, Zhang J, Wu X, Hu J, Yin GC, Xu YJ Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. It is a type of inflammation-related cancer that usually follows liver hepatitis that mostly caused by hepatitis B virus (HBV) in China. However, the metabolism disturbance of HCC and HBV-cirrhosis is not yet fully understood. In addition, there is little research on the relationships between inflammation mediators and HCC. In this study, we investigated serum metabolic abnormalities in HBV-cirrhosis and HCC patients through non-targeted metabolomics and targeted eicosanoid analysis. Metabolomic analysis identified 14 metabolites, i.e. malate, citrate, succinate, lysine, carnitine, proline, ornithine, serine, phenylalanine, tyrosine, arachidonic acid arabinose, galactose and uric acid are consistently altered in HBV-cirrhosis and HCC patients. Meanwhile, eicosanoid analysis uncovered several prostaglandins and leukotrienes are implicated in pathological processes in HBV-cirrhosis and HCC. Finally, these identified biomarkers possessed strong potential to distinguish and diagnose HCC from healthy controls and HBV-cirrhosis patients. This study provided a new perspective to understand the mechanism and discover probable biomarkers of HCC. PMID: 28754861 [PubMed - as supplied by publisher]

Related Articles Immunometabolic and Lipidomic Markers Associated With the Frailty Index and Quality of Life in Aging HIV+ Men on Antiretroviral Therapy. EBioMedicine. 2017 Jul 18;: Authors: Yeoh HL, Cheng AC, Cherry CL, Weir JM, Meikle PJ, Hoy JF, Crowe SM, Palmer CS Abstract Chronic immune activation persists despite antiretroviral therapy (ART) in HIV+ individuals and underpins an increased risk of age-related co-morbidities. We assessed the Frailty Index in older HIV+ Australian men on ART. Immunometabolic markers on monocytes and T cells were analyzed using flow cytometry, plasma innate immune activation markers by ELISA, and lipidomic profiling by mass spectrometry. The study population consisted of 80 HIV+ men with a median age of 59 (IQR, 56-65), and most had an undetectable viral load (92%). 24% were frail, and 76% were non-frail. Frailty was associated with elevated Glucose transporter-1 (Glut1) expression on the total monocytes (p=0.04), increased plasma levels of innate immune activation marker sCD163 (OR, 4.8; CI 1.4-15.9, p=0.01), phosphatidylethanolamine PE(36:3) (OR, 5.1; CI 1.7-15.5, p=0.004) and triacylglycerol TG(16:1_18:1_18:1) (OR, 3.4; CI 1.3-9.2, p=0.02), but decreased expression of GM3 ganglioside, GM3(d18:1/18:0) (OR, 0.1; CI 0.0-0.6, p=0.01) and monohexosylceramide HexCerd(d18:1/22:0) (OR, 0.1; CI 0.0-0.5, p=0.004). There is a strong inverse correlation between quality of life and the concentration of PE(36:3) (ρ=-0.33, p=0.004) and PE(36:4) (ρ=-0.37, p=0.001). These data suggest that frailty is associated with increased innate immune activation and abnormal lipidomic profile. These markers should be investigated in larger, longitudinal studies to determine their potential as biomarkers for frailty. PMID: 28754302 [PubMed - as supplied by publisher]

Related Articles Post-mortem molecular profiling of three psychiatric disorders. Genome Med. 2017 Jul 28;9(1):72 Authors: Ramaker RC, Bowling KM, Lasseigne BN, Hagenauer MH, Hardigan AA, Davis NS, Gertz J, Cartagena PM, Walsh DM, Vawter MP, Jones EG, Schatzberg AF, Barchas JD, Watson SJ, Bunney BG, Akil H, Bunney WE, Li JZ, Cooper SJ, Myers RM Abstract BACKGROUND: Psychiatric disorders are multigenic diseases with complex etiology that contribute significantly to human morbidity and mortality. Although clinically distinct, several disorders share many symptoms, suggesting common underlying molecular changes exist that may implicate important regulators of pathogenesis and provide new therapeutic targets. METHODS: We performed RNA sequencing on tissue from the anterior cingulate cortex, dorsolateral prefrontal cortex, and nucleus accumbens from three groups of 24 patients each diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, and from 24 control subjects. We identified differentially expressed genes and validated the results in an independent cohort. Anterior cingulate cortex samples were also subjected to metabolomic analysis. ChIP-seq data were used to characterize binding of the transcription factor EGR1. RESULTS: We compared molecular signatures across the three brain regions and disorders in the transcriptomes of post-mortem human brain samples. The most significant disease-related differences were in the anterior cingulate cortex of schizophrenia samples compared to controls. Transcriptional changes were assessed in an independent cohort, revealing the transcription factor EGR1 as significantly down-regulated in both cohorts and as a potential regulator of broader transcription changes observed in schizophrenia patients. Additionally, broad down-regulation of genes specific to neurons and concordant up-regulation of genes specific to astrocytes was observed in schizophrenia and bipolar disorder patients relative to controls. Metabolomic profiling identified disruption of GABA levels in schizophrenia patients. CONCLUSIONS: We provide a comprehensive post-mortem transcriptome profile of three psychiatric disorders across three brain regions. We highlight a high-confidence set of independently validated genes differentially expressed between schizophrenia and control patients in the anterior cingulate cortex and integrate transcriptional changes with untargeted metabolite profiling. PMID: 28754123 [PubMed - in process]

Related Articles Chemical Analysis of Astragali Complanati Semen and Its Hypocholesterolemic Effect Using Serum Metabolomics Based on Gas Chromatography-Mass Spectrometry. Antioxidants (Basel). 2017 Jul 21;6(3): Authors: Sham TT, Zhang H, Mok DKW, Chan SW, Wu J, Tang S, Chan CO Abstract The hypocholesterolemic protective effect of the dried seed of Astragalus complanatus (ACS) was investigated in rats fed with normal diet, high cholesterol diet (HCD), and HCD plus 70% ethanol extract of ACS (600 mg/kg/day) by oral gavage for four weeks. ACS extract was tested to be rich in antioxidants, which may be contributed to its high content of phenolic compounds. Consumption of ACS remarkably suppressed the elevated total cholesterol (p < 0.01) and LDL-C (p < 0.001) induced by HCD. Chemical constituents of ACS extract were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization orbitrap mass spectrometry and the results showed that the ACS extract mainly consisted of phenolic compounds including flavonoids and flavonoid glycosides. In addition, based on the serum fatty acid profiles, elucidated using gas chromatography-mass spectrometry, free and esterified fatty acids including docosapentaenoic acid, adrenic acid, dihomo-γ-linolenic acid and arachidonic acid were regulated in ACS treatment group. Western blot results further indicated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) (p < 0.05) in liver was upregulated in ACS treatment group. To conclude, our results clearly demonstrated that ACS provides beneficial effect on lowering HCD associated detrimental change. PMID: 28753987 [PubMed]

Related Articles Inhibitory effects of fifteen phthalate esters in human cDNA-expressed UDP-glucuronosyltransferase supersomes. Chemosphere. 2017 Jul 19;185:983-990 Authors: Cao YF, Du Z, Zhu ZT, Sun HZ, Fu ZW, Yang K, Liu YZ, Hu CM, Dong PP, Gonzalez FJ, Fang ZZ Abstract Phthalate esters (PAEs) have been extensively used in industry as plasticizers and there remains concerns about their safety. The present study aimed to determine the inhibition of phthalate esters (PAEs) on the activity of the phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone was used to investigate the inhibition potentials of PAEs towards various s UGTs. PAEs exhibited no significant inhibition of UGT1A1, UGT1A3, UGT1A8, UGT1A10, UGT2B15, and UGT2B17, and limited inhibition of UGT1A6, UGT1A7 and UGT2B4. However, UGT1A9 was strongly inhibited by PAEs. In silico docking demonstrated a significant contribution of hydrogen bonds and hydrophobic interactions contributing to the inhibition of UGT by PAEs. The Ki values were 15.5, 52.3, 23.6, 12.2, 5.61, 2.79, 1.07, 22.8, 0.84, 73.7, 4.51, 1.74, 0.58, 6.79, 4.93, 6.73, and 7.23 μM for BBOP-UGT1A6, BBZP-UGT1A6, BBOP-UGT1A7, BBZP-UGT1A7, DiPP-UGT1A9, DiBP-UGT1A9, DCHP-UGT1A9, DBP-UGT1A9, BBZP-UGT1A9, BBOP-UGT1A9, DMEP-UGT1A9, DPP-UGT1A9, DHP-UGT1A9, DiBP-UGT2B4, DBP-UGT2B4, DAP-UGT2B4, and BBZP-UGT2B4, respectively. In conclusion, exposure to PAEs might influence the metabolic elimination of endogenous compounds and xenobiotics through inhibiting UGTs. PMID: 28753904 [PubMed - as supplied by publisher]

Related Articles Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder. Eur Urol Focus. 2017 Apr 20;: Authors: Piyarathna DWB, Rajendiran TM, Putluri V, Vantaku V, Soni T, von Rundstedt FC, Donepudi SR, Jin F, Maity S, Ambati CR, Dong J, Gödde D, Roth S, Störkel S, Degener S, Michailidis G, Lerner SP, Pennathur S, Lotan Y, Coarfa C, Sreekumar A, Putluri N Abstract BACKGROUND: The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified. OBJECTIVE: To identify lipidomic signatures associated with survival and different clinical stages of UCB. DESIGN, SETTING, AND PARTICIPANTS: Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75). RESULTS AND LIMITATIONS: UCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study. CONCLUSIONS: To date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression. PATIENT SUMMARY: Lipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder. PMID: 28753886 [PubMed - as supplied by publisher]

Related Articles High-throughput metabolomics for discovering potential metabolite biomarkers and metabolic mechanism from APPswe/PS1dE9 transgenic model of Alzheimer's disease. J Proteome Res. 2017 Jul 28;: Authors: Yu J, Kong L, Zhang A, Han Y, Liu Z, Sun H, Liu L, Wang X Abstract Alzheimer's disease (AD), a neurodegenerative disorder, is the major form of dementia. As AD is an irreversible disease, it is necessary to reinforce earlier intervention. However, the potential biomarkers on preclinical AD are still not clearly. In this study, urinary metabolomics based on ultra-high performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was performed for delineating the metabolic changes and potential early biomarkers in APPswe/PS1dE9 (APP/PS1) transgenic mice. Compared to wide-type, a total of 24 differential metabolites were identified in transgenic mice using multivariate statistical analysis. Among them, 10 metabolites were significantly up-regulated and 14 metabolites were down-regulated. Based on these potential biomarkers, metabolic pathway analysis found that pentose and glucuronate interconversions, glyoxylate and dicarboxylate metabolism, starch and sucrose metabolism, citrate cycle, tryptophan metabolism and arginine and proline metabolism were disturbed in APP/PS1 mice. Our study manifested that endogenous metabolites in the urine of APP/PS1 mice have changed priors to the emergence of learning and cognitive impairment, which may be associated with abnormal NO production pathways and metabolic disorders of the monoaminergic neurotransmitters. In conclusion, this study showed that metabolomics provides an early indicator of the disease occurrence. PMID: 28753016 [PubMed - as supplied by publisher]

Related Articles A Detailed Investigation and Comparison of the XCMS and MZmine 2 Chromatogram Construction and Chromatographic Peak Detection Methods for Preprocessing Mass Spectrometry Metabolomics Data. Anal Chem. 2017 Jul 28;: Authors: Myers OD, Sumner SJ, Li S, Barnes S, Du X Abstract XCMS and MZmine 2 are two widely used software packages for preprocessing untargeted LC/MS metabolomics data. Both construct extracted ion chromatograms (EICs) and detect peaks from the EICs, the first two steps in the data preprocessing workflow. While both packages have performed admirably in peak picking, they also detect a problematic number of false positive EIC peaks and can also fail to detect real EIC peaks. The former and latter translate downstream into spurious and missing compounds, and present significant limitations with most existing software packages that preprocess untargeted mass spectrometry metabolomics data. We seek to understand the specific reasons why XCMS and MZmine 2 find the false positive EIC peaks that they do, and in what ways they fail to detect real compounds. We investigate differences of EIC construction methods in XCMS and MZmine 2 and find several problems in the XCMS centWave peak detection algorithm which we show are partly responsible for the false positive and false negative compound identifications. In addition, we find a problem with MZmine 2's use of centWave. We hope that a detailed understanding of the XCMS and MZmine 2 algorithms will allow users to work with them more effectively, and will also help with future algorithmic development. PMID: 28752757 [PubMed - as supplied by publisher]

Related Articles One Step Forward for Reducing False Positive and False Negative Compound Identifications from Mass Spectrometry Metabolomics Data: New Algorithms for Constructing Extracted Ion Chromatograms and Detecting Chromatographic Peaks. Anal Chem. 2017 Jul 28;: Authors: Myers OD, Sumner SJ, Li S, Barnes S, Du X Abstract False positive and false negative peaks detected from extracted ion chromatograms (EIC) are an urgent problem with existing software packages that preprocess untargeted liquid or gas chromatography-mass spectrometry metabolomics data because they can translate downstream into spurious or missing compound identifications. We have developed new algorithms that carry out the sequential construction of EICs and detection of EIC peaks. We compare the new algorithms to two popular software packages XCMS and MZmine 2, and present evidence that these new algorithms detect significantly fewer false positives. Regarding the detection of compounds known to be present in the data, the new algorithms perform at least as well as XCMS and MZmine 2. Furthermore, we present evidence that mass tolerance in m/z should be favored rather than mass tolerance in ppm in the process of constructing EICs. The mass tolerance parameter plays a critical role in the EIC construction process and can have immense impact on the detection of EIC peaks. PMID: 28752754 [PubMed - as supplied by publisher]

Related Articles NMR-based metabolomics reveals the metabolite profiles of Vibrio parahaemolyticus under ferric iron stimulation. J Microbiol. 2017 Aug;55(8):628-634 Authors: Zhou J, Lu C, Zhang D, Ma C, Su X Abstract Vibrio parahaemolyticus is a halophilic bacterium endemic to coastal areas, and its pathogenicity has caused widespread seafood poisoning. In our previous research, the protein expression of V. parahaemolyticus in Fe(3+) medium was determined using isobaric tags for relative and absolute quantitation (iTRAQ). Here, nuclear magnetic resonance (NMR) was used to detect changes in the V. parahaemolyticus metabolome. NMR spectra were obtained using methanol-water extracts of intracellular metabolites from V. parahaemolyticus under various culture conditions, and 62 metabolites were identified, including serine, arginine, alanine, ornithine, tryptophan, glutamine, malate, NAD(+), NADP(+), oxypurinol, xanthosine, dCTP, uracil, thymine, hypoxanthine, and betaine. Among these, 21 metabolites were up-regulated after the stimulation of the cells by ferric iron, and 9 metabolites were down-regulated. These metabolites are involved in amino acid and protein synthesis, energy metabolism, DNA and RNA synthesis and osmolality. Based on these results, we conclude that Fe(3+) influences the metabolite profiles of V. parahaemolyticus. PMID: 28752295 [PubMed - in process]

Related Articles The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes. Mol Metab. 2017 Aug;6(8):931-940 Authors: Blutke A, Renner S, Flenkenthaler F, Backman M, Haesner S, Kemter E, Ländström E, Braun-Reichhart C, Albl B, Streckel E, Rathkolb B, Prehn C, Palladini A, Grzybek M, Krebs S, Bauersachs S, Bähr A, Brühschwein A, Deeg CA, De Monte E, Dmochewitz M, Eberle C, Emrich D, Fux R, Groth F, Gumbert S, Heitmann A, Hinrichs A, Keßler B, Kurome M, Leipig-Rudolph M, Matiasek K, Öztürk H, Otzdorff C, Reichenbach M, Reichenbach HD, Rieger A, Rieseberg B, Rosati M, Saucedo MN, Schleicher A, Schneider MR, Simmet K, Steinmetz J, Übel N, Zehetmaier P, Jung A, Adamski J, Coskun Ü, Hrabě de Angelis M, Simmet C, Ritzmann M, Meyer-Lindenberg A, Blum H, Arnold GJ, Fröhlich T, Wanke R, Wolf E Abstract OBJECTIVE: The prevalence of diabetes mellitus and associated complications is steadily increasing. As a resource for studying systemic consequences of chronic insulin insufficiency and hyperglycemia, we established a comprehensive biobank of long-term diabetic INS(C94Y) transgenic pigs, a model of mutant INS gene-induced diabetes of youth (MIDY), and of wild-type (WT) littermates. METHODS: Female MIDY pigs (n = 4) were maintained with suboptimal insulin treatment for 2 years, together with female WT littermates (n = 5). Plasma insulin, C-peptide and glucagon levels were regularly determined using specific immunoassays. In addition, clinical chemical, targeted metabolomics, and lipidomics analyses were performed. At age 2 years, all pigs were euthanized, necropsied, and a broad spectrum of tissues was taken by systematic uniform random sampling procedures. Total beta cell volume was determined by stereological methods. A pilot proteome analysis of pancreas, liver, and kidney cortex was performed by label free proteomics. RESULTS: MIDY pigs had elevated fasting plasma glucose and fructosamine concentrations, C-peptide levels that decreased with age and were undetectable at 2 years, and an 82% reduced total beta cell volume compared to WT. Plasma glucagon and beta hydroxybutyrate levels of MIDY pigs were chronically elevated, reflecting hallmarks of poorly controlled diabetes in humans. In total, ∼1900 samples of different body fluids (blood, serum, plasma, urine, cerebrospinal fluid, and synovial fluid) as well as ∼17,000 samples from ∼50 different tissues and organs were preserved to facilitate a plethora of morphological and molecular analyses. Principal component analyses of plasma targeted metabolomics and lipidomics data and of proteome profiles from pancreas, liver, and kidney cortex clearly separated MIDY and WT samples. CONCLUSIONS: The broad spectrum of well-defined biosamples in the Munich MIDY Pig Biobank that will be available to the scientific community provides a unique resource for systematic studies of organ crosstalk in diabetes in a multi-organ, multi-omics dimension. PMID: 28752056 [PubMed - in process]

Related Articles Proteomics Coupled with Metabolite and Cell Wall Profiling Reveal Metabolic Processes of a Developing Rice Stem Internode. Front Plant Sci. 2017;8:1134 Authors: Lin F, Williams BJ, Thangella PAV, Ladak A, Schepmoes AA, Olivos HJ, Zhao K, Callister SJ, Bartley LE Abstract Internodes of grass stems function in mechanical support, transport, and, in some species, are a major sink organ for carbon in the form of cell wall polymers. This study reports cell wall composition, proteomic, and metabolite analyses of the rice elongating internode. Cellulose, lignin, and xylose increase as a percentage of cell wall material along eight segments of the second rice internode (internode II) at booting stage, from the younger to the older internode segments, indicating active cell wall synthesis. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) of trypsin-digested proteins from this internode at booting reveals 2,547 proteins with at least two unique peptides in two biological replicates. The dataset includes many glycosyltransferases, acyltransferases, glycosyl hydrolases, cell wall-localized proteins, and protein kinases that have or may have functions in cell wall biosynthesis or remodeling. Phospho-enrichment of internode II peptides identified 21 unique phosphopeptides belonging to 20 phosphoproteins including a leucine rich repeat-III family receptor like kinase. GO over-representation and KEGG pathway analyses highlight the abundances of proteins involved in biosynthetic processes, especially the synthesis of secondary metabolites such as phenylpropanoids and flavonoids. LC-MS/MS of hot methanol-extracted secondary metabolites from internode II at four stages (booting/elongation, early mature, mature, and post mature) indicates that internode secondary metabolites are distinct from those of roots and leaves, and differ across stem maturation. This work fills a void of in-depth proteomics and metabolomics data for grass stems, specifically for rice, and provides baseline knowledge for more detailed studies of cell wall synthesis and other biological processes characteristic of internode development, toward improving grass agronomic properties. PMID: 28751896 [PubMed]

Related Articles Identification of the Components Involved in Cyclic Di-AMP Signaling in Mycoplasma pneumoniae. Front Microbiol. 2017;8:1328 Authors: Blötz C, Treffon K, Kaever V, Schwede F, Hammer E, Stülke J Abstract Bacteria often use cyclic dinucleotides as second messengers for signal transduction. While the classical molecule c-di-GMP is involved in lifestyle selection, the functions of the more recently discovered signaling nucleotide cyclic di-AMP are less defined. For many Gram-positive bacteria, c-di-AMP is essential for growth suggesting its involvement in a key cellular function. We have analyzed c-di-AMP signaling in the genome-reduced pathogenic bacterium Mycoplasma pneumoniae. Our results demonstrate that these bacteria produce c-di-AMP, and we could identify the diadenylate cyclase CdaM (MPN244). This enzyme is the founding member of a novel family of diadenylate cyclases. Of two potential c-di-AMP degrading phosphodiesterases, only PdeM (MPN549) is active in c-di-AMP degradation, whereas NrnA (MPN140) was reported to degrade short oligoribonucleotides. As observed in other bacteria, both the c-di-AMP synthesizing and the degrading enzymes are essential for M. pneumoniae suggesting control of a major homeostatic process. To obtain more insights into the nature of this process, we have identified a c-di-AMP-binding protein from M. pneumoniae, KtrC. KtrC is the cytoplasmic regulatory subunit of the low affinity potassium transporter KtrCD. It is established that binding of c-di-AMP inhibits the KtrCD activity resulting in a limitation of potassium uptake. Our results suggest that the control of potassium homeostasis is the essential function of c-di-AMP in M. pneumoniae. PMID: 28751888 [PubMed]

Related Articles Impaired Mitochondrial Fusion, Autophagy, Biogenesis and Dysregulated Lipid Metabolism is associated with Preeclampsia. Exp Cell Res. 2017 Jul 24;: Authors: Zhou X, Han TL, Chen H, Baker PN, Qi H, Zhang H Abstract Preeclampsia(PE) is a pregnancy complication that is diagnosed by the new onset of hypertension and proteinuria. The etiology of PE remains unclear; however, growing evidence indicates that mitochondrial impairment contributes to the pathogenesis. Therefore, we aim to investigate the function of mitochondria in the development of PE. The mitochondrial metabolome in preeclamptic (n = 11) and normal (n = 11) placentas were analyzed using Gas chromatography-mass spectrometry (GC-MS). Student's t-tests and receiver operating characteristic (ROC) curves were conducted to determine which mitochondrial metabolites differed significantly between the two groups. The Pathway Activity Profiling (PAPi) R package was used to predict which metabolic pathways were affected by PE. Western blot analysis was performed to identify the candidate proteins which were associated with mitochondrial repair regulation. GC-MS analysis demonstrated that higher levels of 38 metabolites and lower levels of 2 metabolites were observed in the placenta of patients with severe PE (sPE). Five fatty acids had an area under the ROC curve above 90%. Furthermore, we revealed abnormal regulation of mitochondrial dynamics, autophagy, and biogenesis in sPE. Our discoveries indicate that the compromised lipid metabolism in sPE may result from dysfunctional mitochondria, thus revealing new insights into the etiology of the disease. PMID: 28751269 [PubMed - as supplied by publisher]

Related Articles GC-MS based metabolomics used for the identification of cancer volatile organic compounds as biomarkers. J Pharm Biomed Anal. 2017 Jul 17;: Authors: Lubes G, Goodarzi M Abstract A biomarker can be a metabolite, coming from a metabolic pathway or cell process, which might be employed in the diagnostic of diseases, predict patient response towards chemical therapies and/or monitor disease recurrences. Biomarkers, e.g. aldehydes or hydrocarbons, are often identified from different body fluids such as blood, urine, serum, saliva or from various tissues samples, and their concentration can vary from one sample to the other. However, the detection and the action of these biomarkers for diseases is a complicated process. Cancer is one of the main cause of death worldwide. The main characteristic of cancerous tumor is the uncontrolled growing of cells inside the organism. Likely, these uncontrolled growths are as consequence changes in the metabolism that could be analytically monitored. Depending on where the cancer cells are located, they provide different characteristics profiles. These profiles as fingerprints are used for differentiation in a comparison to normal cells. This critical study aimed at highlighting the latest progress in this area, especially in the employment of gas chromatography for the monitoring of volatile organic compounds (VOCs) and the identification of possible molecules used as biomarkers for cancer therapy. PMID: 28750734 [PubMed - as supplied by publisher]