PubMed

Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems. Sci Rep. 2017 Aug 17;7(1):8652 Authors: Udhane SS, Legeza B, Marti N, Hertig D, Diserens G, Nuoffer JM, Vermathen P, Flück CE Abstract Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells. Microarray analysis revealed changes in 693 genes after metformin treatment. Using high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS-NMR), we determined 38 intracellular metabolites. With bioinformatic tools we created an integrated pathway analysis to understand different intracellular processes targeted by metformin. Combined metabolomics and transcriptomics data analysis showed that metformin affects a broad range of cellular processes centered on the mitochondrium. Data confirmed several known effects of metformin on glucose and androgen metabolism, which had been identified in clinical and basic studies previously. But more importantly, novel links between the energy metabolism, sex steroid biosynthesis, the cell cycle and the immune system were identified. These omics studies shed light on a complex interplay between metabolic pathways in steroidogenic systems. PMID: 28819133 [PubMed - in process]

An on-spot internal standard addition approach for accurately determining colistin A and colistin B in dried blood spots using ultra high-performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2017 Aug 03;145:783-793 Authors: Tsai IL, Kuo CH, Sun HY, Chuang YC, Chepyala D, Lin SW, Tsai YJ Abstract Outbreaks of multidrug-resistant Gram-negative bacterial infections have been reported worldwide. Colistin, an antibiotic with known nephrotoxicity and neurotoxicity, is now being used to treat multidrug-resistant Gram-negative strains. In this study, we applied an on-spot internal standard addition approach coupled with an ultra high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify colistin A and B from dried blood spots (DBSs). Only 15μL of whole blood was required for each sample. An internal standard with the same yield of extraction recoveries as colistin was added to the spot before sample extraction for accurate quantification. Formic acid in water (0.15%) with an equal volume of acetonitrile (50:50v/v) was used as the extraction solution. With the optimized extraction process and LC-MS/MS conditions, colistin A and B could be quantified from a DBS with respective limits of quantification of 0.13 and 0.27μgmL(-1), and the retention times were < 2min. The relative standard deviations of within-run and between-run precisions for peak area ratios were all < 17.3%. Accuracies were 91.5-111.2% for lower limit of quantification, low, medium, and high QC samples. The stability of the easily hydrolyzed prodrug, colistin methanesulfonate, was investigated in DBSs. Less than 4% of the prodrug was found to be hydrolyzed in DBSs at room temperature after 48h. The developed method applied an on-spot internal standard addition approach which benefited the precision and accuracy. Results showed that DBS sampling coupled with the sensitive LC-MS/MS method has the potential to be an alternative approach for colistin quantification, where the bias of prodrug hydrolysis in liquid samples is decreased. PMID: 28818804 [PubMed - as supplied by publisher]

Metabolic features involved in drought stress tolerance mechanisms in peanut nodules and their contribution to biological nitrogen fixation. Plant Sci. 2017 Oct;263:12-22 Authors: Furlan AL, Bianucci E, Castro S, Dietz KJ Abstract Legumes belong to the most important crops worldwide. They increase soil fertility due their ability to establish symbiotic associations with soil microorganisms, known as rhizobia, capable of fixing nitrogen from the atmosphere. However, they are frequently exposed to abiotic stress conditions in particular drought. Such adverse conditions impair the biological nitrogen fixation (BNF) and depend largely on the legume. Therefore, two peanut cultivars with contrasting tolerance to drought, namely the more tolerant EC-98 and the sensitive Granoleico, were investigated to elucidate the relative contribution of BNF to the tolerance to drought. The tolerant cultivar EC-98 sustained growth and BNF similar to the control condition despite the reduced water potential and photosynthesis, suggesting the functioning of distinct metabolic pathways that contributed to enhance the tolerance. The biochemical and metabolomics approaches revealed that nodules from the tolerant cultivar accumulated trehalose, proline and gamma-aminobutyric acid (GABA), metabolites with known function in protecting against drought stress. The amide metabolism was severely affected in nodules from the sensitive cultivar Granoleico as revealed by the low content of asparagine and glutamine in the drought stressed plants. The sensitive cultivar upon rehydration was unable to re-establish a metabolism similar to well-watered plants. This was evidenced by the low level of metabolites and, transcripts and specific activities of enzymes from the carbon (sucrose synthase) and nitrogen (glutamine synthetase) metabolism which decreased below the values of control plants. Therefore, the increased content of metabolites with protective functions under drought stress likely is crucial for the full restoration upon rehydration. Smaller changes of drought stress-related metabolites in nodule are another trait that contributes to the effective control of BNF in the tolerant peanut cultivar (EC-98). PMID: 28818367 [PubMed - in process]

Related Articles A Genoproteomic Approach to Detect Peptide Markers of Bacterial Respiratory Pathogens. Clin Chem. 2017 Aug;63(8):1398-1408 Authors: Wang H, Drake SK, Yong C, Gucek M, Lyes MA, Rosenberg AZ, Soderblom E, Arthur Moseley M, Dekker JP, Suffredini AF Abstract BACKGROUND: Rapid identification of respiratory pathogens may facilitate targeted antimicrobial therapy. Direct identification of bacteria in bronchoalveolar lavage (BAL) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is confounded by interfering substances. We describe a method to identify unique peptide markers of 5 gram-negative bacteria by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for direct pathogen identification in BAL. METHODS: In silico translation and digestion were performed on 14-25 whole genomes representing strains of Acinetobacter baumannii, Moraxella catarrhalis, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Klebsiella pneumoniae. Peptides constituting theoretical core peptidomes in each were identified. Rapid tryptic digestion was performed; peptides were analyzed by LC-MS/MS and compared with the theoretical core peptidomes. High-confidence core peptides (false discovery rate <1%) were identified and analyzed with the lowest common ancestor search to yield potential species-specific peptide markers. The species specificity of each peptide was verified with protein BLAST. Further, 1 or 2 pathogens were serially diluted into pooled inflamed BAL, and a targeted LC-MS/MS assay was used to detect 25 peptides simultaneously. RESULTS: Five unique peptides with the highest abundance for each pathogen distinguished these pathogens with varied detection sensitivities. Peptide markers for A. baumannii and P. aeruginosa, when spiked simultaneously into inflamed BAL, were detected with as few as 3.6 (0.2) × 10(3) and 2.2 (0.6) × 10(3) colony-forming units, respectively, by targeted LC-MS/MS. CONCLUSIONS: This proof-of-concept study shows the feasibility of identifying unique peptides in BAL for 5 gram-negative bacterial pathogens, and it may provide a novel approach for rapid direct identification of bacterial pathogens in BAL. PMID: 28588123 [PubMed - indexed for MEDLINE]

Related Articles Allelopatic Potential of Dittrichia viscosa (L.) W. Greuter Mediated by VOCs: A Physiological and Metabolomic Approach. PLoS One. 2017;12(1):e0170161 Authors: Araniti F, Lupini A, Sunseri F, Abenavoli MR Abstract Dittrichia viscosa (L.) W. Greuter is a pioneer species belonging to the Compositae family. It is widespread in the Mediterranean basin, where it is considered invasive. It is a source of secondary metabolites, playing an important ecological role. D. viscosa plant extracts showed a phytotoxic activity on several physiological processes of different species. In the current study, the allelopathic potential of D. viscosa VOCs, released by its foliage, was evaluated on seed germination and root growth of lettuce. The VOCs effect was also studied on lettuce adult plants in microcosm systems, which better mimicked the open field conditions. D. viscosa VOCs inhibited both seed germination and root growth of lettuce. The VOCs composition revealed a large presence of terpenoids, responsible of the effects observed. Moreover, D. viscosa VOCs caused an alteration on plant water status accompanied by oxidative damages and photoinhibition on lettuce adult plants. PMID: 28085959 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic Profiling of the Malaria Box Reveals Antimalarial Target Pathways. Antimicrob Agents Chemother. 2016 Nov;60(11):6635-6649 Authors: Allman EL, Painter HJ, Samra J, Carrasquilla M, Llinás M Abstract The threat of widespread drug resistance to frontline antimalarials has renewed the urgency for identifying inexpensive chemotherapeutic compounds that are effective against Plasmodium falciparum, the parasite species responsible for the greatest number of malaria-related deaths worldwide. To aid in the fight against malaria, a recent extensive screening campaign has generated thousands of lead compounds with low micromolar activity against blood stage parasites. A subset of these leads has been compiled by the Medicines for Malaria Venture (MMV) into a collection of structurally diverse compounds known as the MMV Malaria Box. Currently, little is known regarding the activity of these Malaria Box compounds on parasite metabolism during intraerythrocytic development, and a majority of the targets for these drugs have yet to be defined. Here we interrogated the in vitro metabolic effects of 189 drugs (including 169 of the drug-like compounds from the Malaria Box) using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). The resulting metabolic fingerprints provide information on the parasite biochemical pathways affected by pharmacologic intervention and offer a critical blueprint for selecting and advancing lead compounds as next-generation antimalarial drugs. Our results reveal several major classes of metabolic disruption, which allow us to predict the mode of action (MoA) for many of the Malaria Box compounds. We anticipate that future combination therapies will be greatly informed by these results, allowing for the selection of appropriate drug combinations that simultaneously target multiple metabolic pathways, with the aim of eliminating malaria and forestalling the expansion of drug-resistant parasites in the field. PMID: 27572391 [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 2017/08/18PubMed 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.

35 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 2017/08/17PubMed 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 2017/08/15PubMed 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.

Taurine upregulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma. Hepatology. 2017 Aug 12;: Authors: Lin YH, Wu MH, Huang YH, Yeh CT, Cheng ML, Chi HC, Tsai CY, Chung IH, Chen CY, Lin KH Abstract Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of Taurine upregulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion and glycolysis via suppression of miR-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3'-untranslated region (UTR) of AMP-activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR-455-3p/AMPKβ2 axis regulates cell growth, metastasis and glycolysis through regulation of Hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients. CONCLUSION: Our data collectively highlight that novel regulatory associations among TUG1, miR-455-3p, AMPKβ2 and HK2 are an important determinant of glycolytic metabolism and metastasis in HCC cells and support the potential utility of targeting TUG1/HK2 as a therapeutic strategy for HCC. This article is protected by copyright. All rights reserved. PMID: 28802060 [PubMed - as supplied by publisher]

TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease. Cell. 2017 Aug 10;170(4):649-663.e13 Authors: Ulland TK, Song WM, Huang SC, Ulrich JD, Sergushichev A, Beatty WL, Loboda AA, Zhou Y, Cairns NJ, Kambal A, Loginicheva E, Gilfillan S, Cella M, Virgin HW, Unanue ER, Wang Y, Artyomov MN, Holtzman DM, Colonna M Abstract Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism. PMID: 28802038 [PubMed - in process]

Related Articles Identification and Partial Structural Characterization of Mass Isolated Valsartan and Its Metabolite with Messenger Tagging Vibrational Spectroscopy. J Am Soc Mass Spectrom. 2017 Aug 11;: Authors: Gorlova O, Colvin SM, Brathwaite A, Menges FS, Craig SM, Miller SJ, Johnson MA Abstract Recent advances in the coupling of vibrational spectroscopy with mass spectrometry create new opportunities for the structural characterization of metabolites with great sensitivity. Previous studies have demonstrated this scheme on 300 K ions using very high power free electron lasers in the fingerprint region of the infrared. Here we extend the scope of this approach to a single investigator scale as well as extend the spectral range to include the OH stretching fundamentals. This is accomplished by detecting the IR absorptions in a linear action regime by photodissociation of weakly bound N2 molecules, which are attached to the target ions in a cryogenically cooled, rf ion trap. We consider the specific case of the widely used drug Valsartan and two isomeric forms of its metabolite. Advantages and challenges of the cold ion approach are discussed, including disentangling the role of conformers and the strategic choices involved in the selection of the charging mechanism that optimize spectral differentiation among candidate structural isomers. In this case, the Na(+) complexes are observed to yield sharp resonances in the high frequency NH and OH stretching regions, which can be used to easily differentiate between two isomers of the metabolite. Graphical Abstract ᅟ. PMID: 28801884 [PubMed - as supplied by publisher]

Related Articles Vitamin B6 is essential for serine de novo biosynthesis. J Inherit Metab Dis. 2017 Aug 11;: Authors: Ramos RJ, Pras-Raves ML, Gerrits J, van der Ham M, Willemsen M, Prinsen H, Burgering B, Jans JJ, Verhoeven-Duif NM Abstract Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation. PMID: 28801717 [PubMed - as supplied by publisher]

Related Articles Calcium signaling and cell cycle: Progression or death. Cell Calcium. 2017 Jul 25;: Authors: Humeau J, Bravo-San Pedro JM, Vitale I, Nuñez L, Villalobos C, Kroemer G, Senovilla L Abstract Cytosolic Ca(2+) concentration levels fluctuate in an ordered manner along the cell cycle, in line with the fact that Ca(2+) is involved in the regulation of cell proliferation. Cell proliferation should be an error-free process, yet is endangered by mistakes. In fact, a complex network of proteins ensures that cell cycle does not progress until the previous phase has been successfully completed. Occasionally, errors occur during the cell cycle leading to cell cycle arrest. If the error is severe, and the cell cycle checkpoints work perfectly, this results into cellular demise by activation of apoptotic or non-apoptotic cell death programs. Cancer is characterized by deregulated proliferation and resistance against cell death. Ca(2+) is a central key to these phenomena as it modulates signaling pathways that control oncogenesis and cancer progression. Here, we discuss how Ca(2+) participates in the exogenous and endogenous signals controlling cell proliferation, as well as in the mechanisms by which cells die if irreparable cell cycle damage occurs. Moreover, we summarize how Ca(2+) homeostasis remodeling observed in cancer cells contributes to deregulated cell proliferation and resistance to cell death. Finally, we discuss the possibility to target specific components of Ca(2+) signal pathways to obtain cytostatic or cytotoxic effects. PMID: 28801101 [PubMed - as supplied by publisher]

Related Articles Immediate reduction of serum citrulline but no change of steroid profile after initiation of metformin in individuals with type 2 diabetes. J Steroid Biochem Mol Biol. 2017 Aug 08;: Authors: Breier M, Wahl S, Prehn C, Ferrari U, Sacco V, Weise M, Grallert H, Adamski J, Lechner A Abstract Metformin is the most important first-line treatment for type 2 diabetes mellitus (T2DM) but its exact mode of action remains unknown. In this study, we used targeted metabolomics to gain new insights into the metabolic effects of metformin in humans with T2DM. We also examined changes in the serum steroid hormone profile. We quantified 167 serum metabolites and 19 steroid hormones using liquid chromatography-tandem mass spectrometry at three time points in individuals with previously untreated T2DM: before the start of metformin therapy (time point A), after the first dose (B) and after short-term therapy for 4-6 weeks (C). For metabolite analysis, we split the study cohort into a discovery and a replication study of 88 and 45 subjects, respectively. The statistical analysis was done using linear mixed-effects models. Among the metabolites quantified, citrulline showed the most pronounced changes. Compared to its baseline serum concentration, citrulline was reduced by 17% after the first dose of metformin (p=1.34E-07) and by 24% after short-term therapy (p=2.84E-08) in the discovery study. These results were confirmed in the replication study. The only other metabolite significantly changed after correction for multiple testing was PC ae C36:4 between baseline and 4-6 weeks. The serum steroid hormone profile showed no significant changes after metformin intake. In summary, we observed an immediate and sustained reduction of serum citrulline by metformin in humans. This may be relevant for some of the wanted or unwanted effects of the drug. PMID: 28801099 [PubMed - as supplied by publisher]

Related Articles Solid-phase analytical derivatization for gas-chromatography-mass-spectrometry-based metabolomics. J Biosci Bioeng. 2017 Aug 08;: Authors: Takeo E, Sasano R, Shimma S, Bamba T, Fukusaki E Abstract A novel derivatization method for gas chromatography/mass spectrometry (GC/MS)-based metabolomics was developed, based on solid-phase analytical derivatization (SPAD) with methoximation followed by trimethylsilylation. This SPAD method realized derivatization on solid phases combining strong anion exchange with strong cation exchange. To omit a sample condensation process, GC/MS injection was performed using a large-volume injection mode. This mode uses a stomach-shaped insert, and enables a large quantity of sample to be vaporized and introduced into the GC/MS system. In the present study, several parameters were investigated for each SPAD step. The optimal derivatization conditions were determined to be 3-min-methoximation with 5 μL of >5% methoxyamine solution, and 10-min-trimethylsilylation with 25 μL of N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA). Derivatized analytes were effectively eluted with 25 μL of n-hexane. The influences of coexisting substances were also investigated. Coexisting saccharides did not significantly affect the derivatization of analytes. Moreover, saccharides were efficiently washed out using 80% (v/v) acetonitrile in water. The influences of coexisting sodium chloride were negated by dilution of the sample solution with water. The developed method enables the derivatization of both anionic and cationic metabolites, and high-throughput sample preparation. The coverage of detectable metabolites for the developed method was similar to that of the conventional method. This is the first report of a SPAD-based human plasma metabolome analysis protocol. PMID: 28800906 [PubMed - as supplied by publisher]

Biomarker Research in Parkinson's Disease Using Metabolite Profiling. Metabolites. 2017 Aug 11;7(3): Authors: Havelund JF, Heegaard NHH, Færgeman NJK, Gramsbergen JB Abstract Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifactorial disease, which requires a more precise diagnosis and personalized medication to obtain optimal outcome. In recent years, advanced metabolite profiling of body fluids like serum/plasma, CSF or urine, known as "metabolomics", has become a powerful and promising tool to identify novel biomarkers or "metabolic fingerprints" characteristic for PD at various stages of disease. In this review, we discuss metabolite profiling in clinical and experimental PD. We briefly review the use of different analytical platforms and methodologies and discuss the obtained results, the involved metabolic pathways, the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD. PMID: 28800113 [PubMed]

A Comprehensive Metabolomics Study to Assess Longitudinal Biochemical Changes and Potential Early Biomarkers in NOD Mice that Progress to Diabetes. J Proteome Res. 2017 Aug 11;: Authors: Buchwald P, Tamayo-Garcia A, Ramamoorthy S, Garcia-Contreras M, Mendez AJ, Ricordi C Abstract A global non-targeted longitudinal metabolomics study was carried out in male and female NOD mice to characterize the time-profile of the changes in the metabolic signature caused by onset of type 1 diabetes (T1D) and identify possible early biomarkers in T1D progressors. Metabolomics profiling of samples collected at five different time-points identified 676 and 706 biochemicals in blood and feces, respectively. Several metabolites were expressed at significantly different levels in progressors at all time-points, and their proportion increased strongly following onset of hyperglycemia. At the last time-point, when all progressors were diabetic, a large percentage of metabolites had significantly different levels: 57.8% in blood and 27.8% in feces. Metabolic pathways most strongly affected included the carbohydrate, lipid, branched-chain amino acid, and oxidative ones. Several biochemicals showed considerable (>4×) change. Maltose, 3-hydroxybutyric acid, and kojibiose increased, while 1,5-anhydroglucitol decreased more than 10-fold. At the earliest time-point (6-week), differences between the metabolic signatures of progressors and non-progressors were relatively modest. Nevertheless, several compounds had significantly different levels and show promise as possible early T1D biomarkers. They include fatty acid phosphocholine derivatives from the phosphatidylcholine sub-pathway (elevated in both blood and feces) as well as serotonin, ribose, and arabinose (increased) in blood plus 13-HODE, tocopherol (increased), diaminopimelate, valerate, hydroxymethylpyrimidine, and dulcitol (decreased) in feces. A combined metabolic signature based on these compounds might serve as an early predictor of T1D-progressors. PMID: 28799767 [PubMed - as supplied by publisher]

Related Articles Analysis of Urine Composition in Type II Diabetic Mice after Intervention Therapy Using Holothurian Polypeptides. Front Chem. 2017;5:54 Authors: Li Y, Xu J, Su X Abstract Hydrolysates and peptide fractions (PF) obtained from sea cucumber with commercial enzyme were studied on the hyperglycemic and renal protective effects on db/db rats using urine metabolomics. Compared with the control group the polypeptides from the two species could significantly reduce the urine glucose and urea. We also tried to address the compositions of highly expressed urinary proteins using a proteomics approach. They were serum albumins, AMBP proteins, negative trypsin, elastase, and urinary protein, GAPDH, a receptor of urokinase-type plasminogen activator (uPAR), and Ig kappa chain C region. We used the electronic nose to quickly detect changes in the volatile substances in mice urine after holothurian polypeptides (HPP) fed, and the results show it can identify the difference between treatment groups with the control group without overlapping. The protein express mechanism of HPP treating diabetes was discussed, and we suggested these two peptides with the hypoglycemic and renal protective activity might be utilized as nutraceuticals. PMID: 28798909 [PubMed]

Related Articles High Resolution UHPLC-MS Metabolomics and Sedative-Anxiolytic Effects of Latua pubiflora: A Mystic Plant used by Mapuche Amerindians. Front Pharmacol. 2017;8:494 Authors: Sánchez-Montoya EL, Reyes MA, Pardo J, Nuñez-Alarcón J, Ortiz JG, Jorge JC, Bórquez J, Mocan A, Simirgiotis MJ Abstract Latua pubiflora (Griseb) Phil. Is a native shrub of the Solanaceae family that grows freely in southern Chile and is employed among Mapuche aboriginals to induce sedative effects and hallucinations in religious or medicine rituals since prehispanic times. In this work, the pentobarbital-induced sleeping test and the elevated plus maze test were employed to test the behavioral effects of extracts of this plant in mice. The psychopharmacological evaluation of L. pubiflora extracts in mice determined that both alkaloid-enriched as well as the non-alkaloid extracts produced an increase of sleeping time and alteration of motor activity in mice at 150 mg/Kg. The alkaloid extract exhibited anxiolytic effects in the elevated plus maze test, which was counteracted by flumazenil. In addition, the alkaloid extract from L. pubiflora decreased [(3)H]-flunitrazepam binding on rat cortical membranes. In this study we have identified 18 tropane alkaloids (peaks 1-4, 8-13, 15-18, 21, 23, 24, and 28), 8 phenolic acids and related compounds (peaks 5-7, 14, 19, 20, 22, and 29) and 7 flavonoids (peaks 25-27 and 30-33) in extracts of L. pubiflora by UHPLC-PDA-MS which are responsible for the biological activity. This study assessed for the first time the sedative-anxiolytic effects of L. pubiflora in rats besides the high resolution metabolomics analysis including the finding of pharmacologically important tropane alkaloids and glycosylated flavonoids. PMID: 28798689 [PubMed]