PubMed

Related Articles 'Omic' Approaches to Study Uropathogenic Escherichia coli Virulence. Trends Microbiol. 2017 May 24;: Authors: Lo AW, Moriel DG, Phan MD, Schulz BL, Kidd TJ, Beatson SA, Schembri MA Abstract Uropathogenic Escherichia coli (UPEC) is a pathogen of major significance to global human health and is strongly associated with rapidly increasing antibiotic resistance. UPEC is the primary cause of urinary tract infection (UTI), a disease that involves a complicated pathogenic pathway of extracellular and intracellular lifestyles during interaction with the host. The application of multiple 'omic' technologies, including genomics, transcriptomics, proteomics, and metabolomics, has provided enormous knowledge to our understanding of UPEC biology. Here we outline this progress and present a view for future developments using these exciting forefront technologies to fully comprehend UPEC pathogenesis in the context of infection. PMID: 28550944 [PubMed - as supplied by publisher]

Related Articles Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating. Br J Cancer. 2016 Sep 06;115(6):635-40 Authors: Michalopoulou E, Bulusu V, Kamphorst JJ Abstract Cancer is fundamentally a disease of uncontrolled cell proliferation. Tumour metabolism has emerged as an exciting new discipline studying how cancer cells obtain the necessary energy and cellular 'building blocks' to sustain growth. Glucose and glutamine have long been regarded as the key nutrients fuelling tumour growth. However, the inhospitable tumour microenvironment of certain cancers, like pancreatic cancer, causes the supply of these nutrients to be chronically insufficient for the demands of proliferating cancer cells. Recent work has shown that cancer cells are able to overcome this nutrient insufficiency by scavenging alternative substrates, particularly proteins and lipids. Here, we review recent work identifying the endocytic process of macropinocytosis and subsequent lysosomal processing as an important substrate-acquisition route. In addition, we discuss the impact of hypoxia on fatty acid metabolism and the relevance of exogenous lipids for supporting tumour growth as well as the routes by which tumour cells can access these lipids. Together, these cancer-specific scavenging pathways provide a promising opportunity for therapeutic intervention. PMID: 27537393 [PubMed - indexed for MEDLINE]

Related Articles Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis. J Am Soc Nephrol. 2016 Dec;27(12):3780-3787 Authors: Kurella Tamura M, Chertow GM, Depner TA, Nissenson AR, Schiller B, Mehta RL, Liu S, Sirich TL, FHN Study Abstract Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis. PMID: 27444566 [PubMed - indexed for MEDLINE]

Related Articles Early changes in the metabolic profile of activated CD8(+) T cells. BMC Cell Biol. 2016 Jul 07;17(1):28 Authors: Cammann C, Rath A, Reichl U, Lingel H, Brunner-Weinzierl M, Simeoni L, Schraven B, Lindquist JA Abstract BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes. RESULTS: We found that proliferation inducing conditions result in an increase in key glycolytic metabolites, whereas the citric acid cycle remains unaffected. The upregulation of glycolysis led to a strong lactate production, which depends upon AKT/PKB, but not mTOR. The observed upregulation of lactate dehydrogenase results in increased lactate production, which we found to be dependent on IL-2 and to be required for proliferation. Additionally we observed upregulation of Glucose-transporter 1 (GLUT1) and glucose uptake upon stimulation, which were surprisingly not influenced by AKT inhibition. CONCLUSIONS: Our findings suggest that AKT plays a central role in upregulating glycolysis via induction of lactate dehydrogenase expression, but has no impact on glucose uptake of T cells. Furthermore, under apoptosis inducing conditions, T cells are not able to upregulate glycolysis and induce lactate production. In addition maintaining high glycolytic rates strongly depends on IL-2 production. PMID: 27387758 [PubMed - indexed for MEDLINE]

Related Articles Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017 May 25;7(5):e014932 Authors: Xu H, Wang H, Guan J, Yi H, Qian Y, Zou J, Xia Y, Fu Y, Li X, Jiao X, Huang H, Dong P, Yu Z, Yang J, Xiang M, Li J, Chen Y, Wang P, Sun Y, Li Y, Zheng X, Jia W, Yin S Abstract OBJECTIVES: Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. METHODS/DESIGN: This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. TRIAL REGISTRATION NUMBER: NCT02886156; pre-results. PMID: 28550021 [PubMed - in process]

Related Articles Potential metabolomic biomarkers for reliable diagnosis of Behcet's disease using gas chromatography with time-of-flight mass spectrometry. Joint Bone Spine. 2017 May 23;: Authors: Ahn JK, Kim J, Hwang J, Song J, Kim KH, Cha HS Abstract OBJECTIVES: Although many diagnostic criteria of Behcet's disease (BD) have been developed and revised by experts, diagnosing BD is still complicated and challenging. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. The purposes of this study were to investigate distinctive metabolic changes in serum samples of BD patients and to identify metabolic candidate biomarkers for reliable diagnosis of BD using the metabolomics platform. METHODS: Metabolomic profiling of 90 serum samples from 45 BD patients and 45 healthy controls (HCs) was performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses. RESULTS: A total of 104 metabolites were identified from samples. The serum metabolite profiles obtained from GC/TOF-MS analysis can distinguish BD patients from HC group in discovery set. The variation values of the partial least squared-discrimination analysis (PLS-DA) model are R(2)X of 0.246, R(2)Y of 0.913, and Q(2) of 0.852, respectively, indicating strong explanation and prediction capabilities of the model. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid, and oleic acid were selected and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.998) in the discovery set and independent set. The principal component analysis showed clear discrimination of BD and HC groups by the five metabolic biomarkers in independent set. CONCLUSIONS: This is the first report on characteristic metabolic profiles and potential metabolite biomarkers in serum for reliable diagnosis of BD using GC/TOF-MS. PMID: 28549946 [PubMed - as supplied by publisher]

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]