PubMed

Related Articles In vitro Metabolomic Approaches to Investigating the Potential Biological Effects of Phenolic Compounds: An Update. Genomics Proteomics Bioinformatics. 2017 May 23;: Authors: Catalán Ú, Barrubés L, Valls RM, Solà R, Rubió L Abstract Dietary phenolic compounds (PCs) have been receiving interest for their presumed roles in disease prevention. However, there is a lack of studies on the underlying molecular mechanisms. In this regard, in vitro metabolomic approaches are suitable for the investigation of the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been examined for PCs from rosemary (Rosmarinus officinalis), olive oil, and resveratrol using cell-based metabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vitro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro- and micro-nutrient metabolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerative diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are needed and testing the physiological conjugated forms of PCs in these cell systems could be of special interest. PMID: 28549934 [PubMed - as supplied by publisher]

Related Articles Glycyrrhizin and glycyrrhetinic acid inhibits alpha-naphthyl isothiocyanate-induced liver injury and bile acid cycle disruption. Toxicology. 2017 May 23;: Authors: Wang H, Fang ZZ, Meng R, Cao YF, Tanaka N, Krausz KW, Gonzalez FJ Abstract Alpha-naphthyl isothiocyanate (ANIT) is a common hepatotoxicant experimentally used to reproduce the pathologies of drug-induced liver injury in humans, but the mechanism of its toxicity remains unclear. To determine the metabolic alterations following ANIT exposure, metabolomic analyses was performed by use of liquid chromatography-mass spectrometry. Partial least squares discriminant analysis (PLS-DA) of liver, serum, bile, ileum, and cecum of vehicle- and ANIT-treated mice revealed significant alterations of individual bile acids, including increased tauroursodeoxycholic acid, taurohydrodeoxycholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid, and decreased ω-, β- and tauro-α/β- murideoxycholic acid, cholic acid, and taurocholic acid in the ANIT-treated groups. In accordance with these changes, ANIT treatment altered the expression of mRNAs encoded by genes responsible for the metabolism and transport of bile acids and cholesterol. Pre-treatment of glycyrrhizin (GL) and glycyrrhetinic acid (GA) prevented ANIT-induced liver damage and reversed the alteration of bile acid metabolites and Cyp7a1, Npc1l1, Mttp, and Acat2 mRNAs encoding bile acid transport and metabolism proteins. These results suggested that GL/GA could prevent drug-induced liver injury and ensuing disruption of bile acid metabolism in humans. PMID: 28549656 [PubMed - as supplied by publisher]

Related Articles Dietary salecan reverts partially the metabolic gene expressions and NMR-based metabolomic profiles from high-fat-diet-induced obese rats. J Nutr Biochem. 2017 May 05;47:53-62 Authors: Sun Q, Li M, Yang X, Xu X, Wang J, Zhang J Abstract Previous studies suggest that dietary salecan (a water-soluble β-glucan) effectively reduces high-fat-diet-induced adiposity through disturbing bile-acid-promoted emulsification in mice. However, the effects of salecan on metabolic genes and metabolites involved in lipid accumulation are mostly unknown. Here, we confirmed that dietary 3% and 6% salecan for 4 weeks markedly decreased fat accumulation in liver and adipose tissue in high-fat-diet rats, displaying a decrease in mRNA levels of SREBP1-C, FAS, SCD1 and ACC1 involved in de novo lipogenesis and a reduction of levels of GPAT1, DGAT1 and DGAT2 related to triglyceride synthesis. Dietary salecan also increased the mRNA levels of PPARα and CYP7A1, which are related to fatty acid oxidation and cholesterol decomposition, respectively. In the (1)H nuclear magnetic resonance metabolomic analysis, both the serum and liver metabolite profiles differed among the control groups, and the metabolic profiles of the salecan groups were shifted toward that of the low-fat-diet group. Metabolites analysis showed that salecan significantly increased hepatic glutathione and betaine levels which are related to regulation of cellular reactive oxygen species. These data demonstrate that dietary salecan not only disturbed fat digestion and absorption but also influenced lipid accumulation and metabolism in diet-induced obesity. PMID: 28549240 [PubMed - as supplied by publisher]

Related Articles Bile acids and tryptophan metabolism are novel pathways involved in metabolic abnormalities in BPA-exposed pregnant mice and male offspring. Endocrinology. 2017 May 25;: Authors: Susiarjo M, Xin F, Stefaniak M, Mesaros C, Simmons RA, Bartolomei MS Abstract Increasing evidence has demonstrated that exposure to endocrine disrupting chemicals (EDCs) impacts maternal and fetal health, but the underlying mechanisms are still unclear. We have previously shown that dietary exposure to 10 µg/kg bw/day and 10 mg/kg bw/day bisphenol A (BPA) during pregnancy induced metabolic abnormalities in F1 male offspring and gestational glucose intolerance in F0 pregnant mice. The aim of this study is to elucidate the underlying etiologies of BPA exposure-induced metabolic disease by analyzing male fetal liver metabolome. Using the Metabolon Discover HD4 Platform, our laboratory has identified metabolic pathways that are altered by BPA exposure including biochemicals in lipid and amino acid metabolism. Specifically, primary and secondary bile acids were increased in liver from BPA-exposed embryonic day (E) 18.5 male fetuses. We subsequently showed that increased bile acid was associated with defective Fxr- dependent negative feedback mechanism in BPA exposed-fetuses. Additionally, through metabolomics, we observed that BPA-exposed fetuses had elevated tryptophan levels. Independent liquid chromatography and mass spectrometry (LC-MS) measurement revealed that BPA-exposed dams also had increased tryptophan relative to controls. Because several key enzymes in tryptophan catabolism are vitamin B6-dependent and vitamin B6 deficiencies have been previously linked to gestational diabetes, we tested the impact of vitamin B6 supplementation and showed that it rescued gestational glucose intolerance in BPA-exposed pregnant mice. Our study has therefore identified two novel pathways (bile acid and tryptophan metabolism) that potentially underlie BPA-induced maternal and fetal metabolic disease. PMID: 28549143 [PubMed - as supplied by publisher]

Related Articles Everolimus inhibited multiple isoforms of UDP-glucuronosyltransferases (UGTs). Xenobiotica. 2017 May 26;:1-21 Authors: Du Z, Wang G, Cao YF, Hu CM, Yang K, Liu YZ, Zhang CZ, Zhang WH, Zhu ZT, Sun HZ, Sun XY, Hong M, Fang ZZ Abstract 1. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and has been clinically utilized to prevent the rejection of organ transplants. This study aims to determine the inhibition of everolimus on the activity of phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). 2. The results showed that 100 uM of everolimus exerted more than 80% inhibition towards UGT1A1, -1A3, and -2B7. UGT1A3 and UGT2B7 were selected to elucidate the inhibition mechanism, and in silico docking showed that hydrogen bonds and hydrophobic interactions mainly contributed to the strong binding of everolimus towards the activity cavity of UGT1A3 and UGT2B7. Inhibition kinetic type analysis using Lineweaver-Burk plot showed competitive inhibition towards all these UGT isoforms. The inhibition kinetic parameters (Ki) were calculated to be 2.3, 0.07, and 4.4 uM for the inhibition of everolimus towards UGT1A1, -1A3, and -2B7, respectively. 3. In vitro-in vivo extrapolation (IVIVE) showed that [I]/Ki value was calculated to be 0.004, 0.14, and 0.002 for UGT1A1, -1A3, and -2B7, respectively. Therefore, high DDI potential existed between everolimus and clinical drugs mainly undergoing UGT1A3-catalyzed glucuronidation. PMID: 28548030 [PubMed - as supplied by publisher]

Related Articles Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties. Rice (N Y). 2017 Dec;10(1):24 Authors: Zarei I, Brown DG, Nealon NJ, Ryan EP Abstract BACKGROUND: Rice bran is a functional food that has shown protection against major chronic diseases (e.g. obesity, diabetes, cardiovascular disease and cancer) in animals and humans, and these health effects have been associated with the presence of bioactive phytochemicals. Food metabolomics uses multiple chromatography and mass spectrometry platforms to detect and identify a diverse range of small molecules with high sensitivity and precision, and has not been completed for rice bran. RESULTS: This study utilized global, non-targeted metabolomics to identify small molecules in rice bran, and conducted a comprehensive search of peer-reviewed literature to determine bioactive compounds. Three U.S. rice varieties (Calrose, Dixiebelle, and Neptune), that have been used for human dietary intervention trials, were assessed herein for bioactive compounds that have disease control and prevention properties. The profiling of rice bran by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) identified 453 distinct phytochemicals, 209 of which were classified as amino acids, cofactors & vitamins, and secondary metabolites, and were further assessed for bioactivity. A scientific literature search revealed 65 compounds with health properties, 16 of which had not been previously identified in rice bran. This suite of amino acids, cofactors & vitamins, and secondary metabolites comprised 46% of the identified rice bran metabolome, which substantially enhanced our knowledge of health-promoting rice bran compounds provided during dietary supplementation. CONCLUSION: Rice bran metabolite profiling revealed a suite of biochemical molecules that can be further investigated and exploited for multiple nutritional therapies and medical food applications. These bioactive compounds may also be biomarkers of dietary rice bran intake. The medicinal compounds associated with rice bran can function as a network across metabolic pathways and this metabolite network may occur via additive and synergistic effects between compounds in the food matrix. PMID: 28547736 [PubMed - in process]

Related Articles Novel urinary metabolite signature for diagnosing postpartum depression. Neuropsychiatr Dis Treat. 2017;13:1263-1270 Authors: Lin L, Chen XM, Liu RH Abstract BACKGROUND: Postpartum depression (PPD) could affect ~10% of women and impair the quality of mother-infant interactions. Currently, there are no objective methods to diagnose PPD. Therefore, this study was conducted to identify potential biomarkers for diagnosing PPD. MATERIALS AND METHODS: Morning urine samples of PPD subjects, postpartum women without depression (PPWD) and healthy controls (HCs) were collected. The gas chromatography-mass spectroscopy (GC-MS)-based urinary metabolomic approach was performed to characterize the urinary metabolic profiling. The orthogonal partial least-squares-discriminant analysis (OPLS-DA) was used to identify the differential metabolites. The logistic regression analysis and Bayesian information criterion rule were further used to identify the potential biomarker panel. The receiver operating characteristic curve analysis was conducted to evaluate the diagnostic performance of the identified potential biomarker panel. RESULTS: Totally, 73 PPD subjects, 73 PPWD and 74 HCs were included, and 68 metabolites were identified using GC-MS. The OPLS-DA model showed that there were 22 differential metabolites (14 upregulated and 8 downregulated) responsible for separating PPD subjects from HCs and PPWD. Meanwhile, a panel of five potential biomarkers - formate, succinate, 1-methylhistidine, α-glucose and dimethylamine - was identified. This panel could effectively distinguish PPD subjects from HCs and PPWD with an area under the curve (AUC) curve of 0.948 in the training set and 0.944 in the testing set. CONCLUSION: These results demonstrated that the potential biomarker panel could aid in the future development of an objective diagnostic method for PPD. PMID: 28546751 [PubMed - in process]

Related Articles Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity. Int J Obes (Lond). 2017 May 26;: Authors: Couto Alves A, Valcarcel B, Mäkinen VP, Morin-Papunen L, Sebert S, Kangas AJ, Soininen P, Das S, De Iorio M, Coin L, Ala-Korpela M, Järvelin MR, Franks S Abstract BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with metabolic disturbances including obesity, insulin resistance, and diabetes mellitus. Here we investigate whether changes in the metabolic profile of PCOS women are driven by increased tendency to obesity or are specific features of PCOS related to increased testosterone levels. DESIGN AND METHODS: We conducted an NMR metabolomics association study of PCOS cases (n=145) and controls (n=687) nested in a population-based birth cohort (n=3,127). Subjects were 31 years old at examination. The main analyses were adjusted for waist circumference (WC) as a proxy measure of central obesity. Subsequently, metabolite concentrations were compared between cases and controls within pre-defined WC strata. On each stratum, additional metabolomics association analyses with testosterone levels were conducted separately among cases and controls. RESULTS: Overall, women with PCOS showed more adverse metabolite profiles than the controls. Four lipid fractions in different subclasses of very low density lipoprotein (VLDL) were associated with PCOS, after adjusting for WC and correction for multiple testing (P<0.002). In stratified analysis the PCOS women within large WC strata (≥98 cm) had significantly lower high density lipoprotein (HDL) levels, ApoA1 and albumin values compared to the controls. Testosterone levels were significantly associated with VLDL and serum lipids in PCOS cases with large WC but not in the controls. The higher testosterone levels, adjusted for WC, adversely associated with insulin levels and HOMA IR in cases but not in the controls. CONCLUSIONS: Our findings show that both abdominal obesity and hyperandrogenism contribute to the dyslipidaemia and other metabolic traits of PCOS which all may negatively contribute to the long term health of women with PCOS.International Journal of Obesity accepted article preview online, 26 May 2017. doi:10.1038/ijo.2017.126. PMID: 28546543 [PubMed - as supplied by publisher]

Related Articles A sensitive mass spectrometry platform identifies metabolic changes of life history traits in C. elegans. Sci Rep. 2017 May 25;7(1):2408 Authors: Gao AW, Chatzispyrou IA, Kamble R, Liu YJ, Herzog K, Smith RL, van Lenthe H, Vervaart MAT, van Cruchten A, Luyf AC, van Kampen A, Pras-Raves ML, Vaz FM, Houtkooper RH Abstract Abnormal nutrient metabolism is a hallmark of aging, and the underlying genetic and nutritional framework is rapidly being uncovered, particularly using C. elegans as a model. However, the direct metabolic consequences of perturbations in life history of C. elegans remain to be clarified. Based on recent advances in the metabolomics field, we optimized and validated a sensitive mass spectrometry (MS) platform for identification of major metabolite classes in worms and applied it to study age and diet related changes. Using this platform that allowed detection of over 600 metabolites in a sample of 2500 worms, we observed marked changes in fatty acids, amino acids and phospholipids during worm life history, which were independent from the germ-line. Worms underwent a striking shift in lipid metabolism after early adulthood that was at least partly controlled by the metabolic regulator AAK-2/AMPK. Most amino acids peaked during development, except aspartic acid and glycine, which accumulated in aged worms. Dietary intervention also influenced worm metabolite profiles and the regulation was highly specific depending on the metabolite class. Altogether, these MS-based methods are powerful tools to perform worm metabolomics for aging and metabolism-oriented studies. PMID: 28546536 [PubMed - in process]

Related Articles Autophagy and Mitophagy in Cardiovascular Disease. Circ Res. 2017 May 26;120(11):1812-1824 Authors: Bravo-San Pedro JM, Kroemer G, Galluzzi L Abstract Autophagy contributes to the maintenance of intracellular homeostasis in most cells of cardiovascular origin, including cardiomyocytes, endothelial cells, and arterial smooth muscle cells. Mitophagy is an autophagic response that specifically targets damaged, and hence potentially cytotoxic, mitochondria. As these organelles occupy a critical position in the bioenergetics of the cardiovascular system, mitophagy is particularly important for cardiovascular homeostasis in health and disease. Consistent with this notion, genetic defects in autophagy or mitophagy have been shown to exacerbate the propensity of laboratory animals to spontaneously develop cardiodegenerative disorders. Moreover, pharmacological or genetic maneuvers that alter the autophagic or mitophagic flux have been shown to influence disease outcome in rodent models of several cardiovascular conditions, such as myocardial infarction, various types of cardiomyopathy, and atherosclerosis. In this review, we discuss the intimate connection between autophagy, mitophagy, and cardiovascular disorders. PMID: 28546358 [PubMed - in process]

Related Articles Alterations in metabolic pathways in stomach of mice infected with Helicobacter pylori. Microb Pathog. 2017 May 22;: Authors: Nishiumi S, Yoshida M, Azuma T Abstract Numerous studies of Helicobacter pylori (H. pylori) have been performed, but few studies have evaluated the effects of H. pylori infections using metabolome analysis, which involves the comprehensive study of low molecular weight metabolites. In this study, the metabolites in the stomach tissue of mice that had been infected with H. pylori SS1 for 1, 3, or 6 months were analyzed, and then evaluations of various metabolic pathways were performed to gain novel understandings of H. pylori infections. As a result, it was found that the glycolytic pathway, the tricarboxylic acid cycle, and the choline pathway tended to be upregulated at 1 month after the H. pylori SS1 infection. The urea cycle tended to be downregulated at 6 months after the infection. High levels of some amino acids were observed in the stomach tissue of the H. pylori SS1-infected mice at 1 month after the infection, whereas low levels of many amino acids were detected at 3 and 6 months after the infection. These results suggest that H. pylori infection causes various metabolic alterations at lesional sites, and these alterations might be linked to the crosstalk between H. pylori and the host leading to transition of disease conditions. PMID: 28546118 [PubMed - as supplied by publisher]

Related Articles Urinary metabolomics study on the protective role of Orthosiphon stamineus in Streptozotocin induced diabetes mellitus in rats via (1)H NMR spectroscopy. BMC Complement Altern Med. 2017 May 25;17(1):278 Authors: Azam AA, Pariyani R, Ismail IS, Ismail A, Khatib A, Abas F, Shaari K Abstract BACKGROUND: Orthosiphon stamineus (OS) is a herb known in ethnomedicine for treating diabetes mellitus (DM). In this study, a (1)H NMR based urine metabolomics tool has been used for the first time to identify the metabolic protective mechanism of OS in DM using Streptozotocin (STZ) induced experimental model in rats. METHODS: Four different solvent extracts of OS, namely aqueous, ethanolic, 50% aqueous ethanolic and methanolic, at a dose of 500 mg/kg body weight (bw) were orally administered for 14 days to diabetic rats induced via intraperitoneal injection of 60 mg/kg bw STZ. NMR metabolomics approach using pattern recognition combined with multivariate statistical analysis was applied in the rat urine to study the resulted metabolic perturbations. RESULTS: OS aqueous extract (OSAE) caused a reversal of DM comparable to that of 10 mg/kg bw glibenclamide. A total of 15 urinary metabolites, which levels changed significantly upon treatment were identified as the biomarkers of OSAE in diabetes. A systematic metabolic pathways analysis identified that OSAE contributed to the antidiabetic activity mainly through regulating the tricarboxylic acid cycle, glycolysis/gluconeogenesis, lipid and amino acid metabolism. CONCLUSIONS: The results of this study validated the ethnopharmacological use of OS in diabetes and unveiled the biochemical and metabolic mechanisms involved. PMID: 28545435 [PubMed - in process]

Related Articles Metabolic profiling of five flavonoids from Dragon's Blood in human liver microsomes using high-performance liquid chromatography coupled with high resolution mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 May 01;1052:91-102 Authors: Li Y, Zhang Y, Wang R, Wei L, Deng Y, Ren W Abstract Although much is known about the pharmacological activities of Dragon's Blood (DB, a traditional Chinese herb), its metabolism in human liver microsomes (HLMs) and the cytochrome P450 (CYP) enzymes has not been studied. This study aims to identify the metabolic profile of five flavonoids (loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone) from DB in HLMs as well as the CYP enzymes that are involved in the metabolism of them. High-resolution mass spectrometry was used to characterize the structures of their metabolites and 10 cDNA-expressed CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) were used to verify which isozymes mediate in the metabolism of the metabolites. Totally, 29 metabolites including 10 metabolites of loureirin A, 10 metabolites of loureirin B, 4 metabolites of loureirin C, 2 metabolites of 7,4'-dihydroxyflavone and 3 metabolites of 5,7,4'-trihydroxyflavanone were elucidated and identified on the basis of the high-resolution MS(n) data. The metabolic profile of the five flavonoids in HLMs involved hydroxylation, oxidation and demethylation. Among them, hydroxylation was the predominant biotransformation of the five flavonoids in HLMs, occurring in combination with other metabolic reactions. Assay with recombinant P450s revealed that CYP2C9 and CYP2C19 played an important role in the hydroxylation of flavonoids in HLMs. To the best of our knowledge, this is the first in vitro evaluation of the metabolic profile of loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone in HLMs. PMID: 28376352 [PubMed - indexed for MEDLINE]

Related Articles Effect of Furan Fatty Acids and 3-Methyl-2,4-nonanedione on Light-Induced Off-Odor in Soybean Oil. J Agric Food Chem. 2017 Mar 15;65(10):2136-2140 Authors: Sano T, Okabe R, Iwahashi M, Imagi J, Sato T, Yamashita T, Fukusaki E, Bamba T Abstract Soybean oil is one of the most widely consumed vegetable oils. However, under photooxidative conditions, this oil develops a beany and green off-odor through a mechanism that has not yet been elucidated. Upon photooxidation, 3-methyl-2,4-nonanedione (3-MND) produces a strong aroma. In this study, the effect of furan fatty acids and 3-MND on odor reversion in soybean oil was investigated. Our findings suggest that the observed light-induced off-odor was likely attributable to the furan fatty acids present in the oil through the generation of 3-MND. While 3-MND may not be directly responsible for the development of light-induced off-odor, this compound appears to be involved because off-odor was detected in canola oil samples containing added 3-MND. In addition, in the present work, 3-hydroxy-3-methyl-2,4-nonanedione, which is derived from 3-MND, was identified for the first time in light-exposed soybean oil and shown to be one of the compounds responsible for odor reversion. PMID: 28215079 [PubMed - indexed for MEDLINE]

Related Articles CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs. J Cell Biol. 2017 Mar 06;216(3):675-693 Authors: Schatton D, Pla-Martin D, Marx MC, Hansen H, Mourier A, Nemazanyy I, Pessia A, Zentis P, Corona T, Kondylis V, Barth E, Schauss AC, Velagapudi V, Rugarli EI Abstract Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target messenger RNAs. In the absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the fetal-neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions. PMID: 28188211 [PubMed - indexed for MEDLINE]

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Related Articles Gastric cancer: Metabolic and metabolomics perspectives (Review). Int J Oncol. 2017 May 16;: Authors: Xiao S, Zhou L Abstract Gastric cancer is one of the most malignant tumors worldwide and remains a major health threat in Asia-Pacific regions, while its pathological mechanism is generally unknown. Recent research has advanced the understanding of the relationship between metabolic reprogramming and carcinogenesis. In particular, metabolic regulation and cancer research are being further brought into sharp focus with the emergence of metabolomics. Not only can metabolomics provide global information on metabolic profiles of specific tumors, but it can also act as a promising tool to discover biomarkers regarding diagnosis, metastatic surveillance and chemotherapeutic sensitivity prediction. Meanwhile, metabolism-based anticancer therapies will be further discovered. Up to now, accumulative studies have highlighted the application of metabolomics in gastric cancer research regarding different aspects; therefore we summarized the current available results of how metabolic changes are linked to gastric carcinogenesis, and how metabolomics holds promise for the diagnosis, metastatic surveillance, treatment and prognosis prediction of gastric cancer. PMID: 28535006 [PubMed - as supplied by publisher]

Related Articles Metabolomics for improving pregnancy outcomes in women undergoing assisted reproductive technologies. Cochrane Database Syst Rev. 2017 May 23;5:CD011872 Authors: Siristatidis CS, Sertedaki E, Vaidakis D Abstract BACKGROUND: In order to overcome the low effectiveness of assisted reproductive technologies (ART) and the high incidence of multiple births, metabolomics is proposed as a non-invasive method to assess oocyte quality, embryo viability, and endometrial receptivity, and facilitate a targeted subfertility treatment. OBJECTIVES: To evaluate the effectiveness and safety of metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity for improving live birth or ongoing pregnancy rates in women undergoing ART, compared to conventional methods of assessment. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL and two trial registers (November 2016). We also examined the reference lists of primary studies and review articles, citation lists of relevant publications, and abstracts of major scientific meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) on metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity in women undergoing ART. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary outcomes were rates of live birth or ongoing pregnancy (composite outcome) and miscarriage. Secondary outcomes were clinical pregnancy, multiple and ectopic pregnancy, cycle cancellation, and foetal abnormalities. We combined data to calculate odds ratios (ORs) for dichotomous data and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: We included four trials with a total of 802 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity.We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.11, 95% CI 0.83 to 1.48; I² = 0%; four RCTs; N = 802), or miscarriage (OR 0.96, 95% CI 0.52 to 1.78; I² = 0%; two RCTs; N = 434). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.99, 95% CI 0.71 to 1.38; I² = 0%; two RCTs; N = 621). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics.We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.22, 95% CI 0.92 to 1.62; I²= 26%; four trials; N = 802), or multiple pregnancy (OR 1.52, 95% CI 0.71 to 3.23; I² = 0%; two RCTs, N = 181). There was very low-quality evidence of little or no difference between groups in ectopic pregnancy rates (OR 3.37, 95% CI 0.14 to 83.40; one RCT; N = 309), and foetal abnormalities (no events; one RCT; N = 125), and very low-quality evidence of higher rates of cycle cancellation in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.14, 95% CI 0.83 to 1.57; I² = 0%; two RCTs; N = 621).The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials. AUTHORS' CONCLUSIONS: According to current trials in women undergoing ART, there is insufficient evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, or miscarriage rates. The existing evidence varied from very low to low-quality. Data on adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available. PMID: 28534597 [PubMed - as supplied by publisher]

Related Articles The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid and endocannabinoid metabolites associated with inflammation in vivo. Metabolomics. 2016 Oct;12(10): Authors: Willis MS, Ilaiwy A, Montgomery MD, Simpson PC, Jensen BC Abstract INTRODUCTION: Alpha-1-adrenergic receptors (α1-ARs) are G-protein coupled receptors (GPCRs) with three highly homologous subtypes (α1A, α1B, and α1D). Of these three subtypes, only the α1A and α1B are expressed in the heart. Multiple pre-clinical models of heart injury demonstrate cardioprotective roles for the α1A. Non-selective α1-AR activation promotes glycolysis in the heart, but the functional α1-AR subtype and broader metabolic effects have not been studied. OBJECTIVES: Given the high metabolic demands of the heart and previous evidence indicating benefit from α1A activation, we chose to investigate the effects of α1A activation on the cardiac metabolome in vivo. METHODS: Mice were treated for one week with a low, subpressor dose of A61603, a highly selective and potent α1A agonist. Cardiac tissue and serum were analyzed using a non-targeted metabolomics approach. RESULTS: We identified previously unrecognized metabolic responses to α1A activation, most notably broad reduction in the abundance of polyunsaturated fatty acids (PUFAs) and endocannabinoids (ECs). CONCLUSION: Given the well characterized roles of PUFAs and ECs in inflammatory pathways, these findings suggest a possible role for cardiac α1A-ARs in the regulation of inflammation and may offer novel insight into the mechanisms underlying the cardioprotective benefit of selective pharmacologic α1A activation. PMID: 28533737 [PubMed - in process]

Related Articles Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes. Sci Rep. 2017 May 22;7(1):2235 Authors: Piontek U, Wallaschofski H, Kastenmüller G, Suhre K, Völzke H, Do KT, Artati A, Nauck M, Adamski J, Friedrich N, Pietzner M Abstract The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population consisted of 430 men and 343 women, aged 20-80 years, who were recruited for the cross-sectional population-based Study of Health in Pomerania (SHIP-TREND), Germany. We used linear regression models to identify associations between testosterone, androstenedione and dehydroepiandrosterone-sulfate (DHEAS) as well as sex hormone-binding globulin and plasma or urine metabolites measured by mass spectrometry. The analyses revealed major sex-specific differences in androgen-associated metabolites, particularly for levels of urate, lipids and metabolic surrogates of lifestyle factors, like cotinine or piperine. In women, in particular in the postmenopausal state, androgens showed a greater impact on the metabolome than in men (especially DHEAS and lipids were highly related in women). We observed a novel association of androstenedione on the metabolism of biogenic amines and only a small sex-overlap of associations within steroid metabolism. The present study yields new insights in the interaction between androgens and metabolism, especially about their implication in female metabolism. PMID: 28533544 [PubMed - in process]