PubMed

Related Articles Digging into the low molecular weight peptidome with the OligoNet web server. Sci Rep. 2017 Sep 15;7(1):11692 Authors: Liu Y, Forcisi S, Lucio M, Harir M, Bahut F, Deleris-Bou M, Krieger-Weber S, Gougeon RD, Alexandre H, Schmitt-Kopplin P Abstract Bioactive peptides play critical roles in regulating many biological processes. Recently, natural short peptides biomarkers are drawing significant attention and are considered as "hidden treasure" of drug candidates. High resolution and high mass accuracy provided by mass spectrometry (MS)-based untargeted metabolomics would enable the rapid detection and wide coverage of the low-molecular-weight peptidome. However, translating unknown masses (<1 500 Da) into putative peptides is often limited due to the lack of automatic data processing tools and to the limit of peptide databases. The web server OligoNet responds to this challenge by attempting to decompose each individual mass into a combination of amino acids out of metabolomics datasets. It provides an additional network-based data interpretation named "Peptide degradation network" (PDN), which unravels interesting relations between annotated peptides and generates potential functional patterns. The ab initio PDN built from yeast metabolic profiling data shows a great similarity with well-known metabolic networks, and could aid biological interpretation. OligoNet allows also an easy evaluation and interpretation of annotated peptides in systems biology, and is freely accessible at https://daniellyz200608105.shinyapps.io/OligoNet/ . PMID: 28916823 [PubMed - in process]

Related Articles Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc Natl Acad Sci U S A. 2017 Sep 15;: Authors: Mills RJ, Titmarsh DM, Koenig X, Parker BL, Ryall JG, Quaife-Ryan GA, Voges HK, Hodson MP, Ferguson C, Drowley L, Plowright AT, Needham EJ, Wang QD, Gregorevic P, Xin M, Thomas WG, Parton RG, Nielsen LK, Launikonis BS, James DE, Elliott DA, Porrello ER, Hudson JE Abstract The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of an adult. However, the key drivers of this process remain poorly defined. We are currently unable to recapitulate postnatal maturation in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), limiting their potential as a model system to discover regenerative therapeutics. Here, we provide a summary of our studies, where we developed a 96-well device for functional screening in human pluripotent stem cell-derived cardiac organoids (hCOs). Through interrogation of >10,000 organoids, we systematically optimize parameters, including extracellular matrix (ECM), metabolic substrate, and growth factor conditions, that enhance cardiac tissue viability, function, and maturation. Under optimized maturation conditions, functional and molecular characterization revealed that a switch to fatty acid metabolism was a central driver of cardiac maturation. Under these conditions, hPSC-CMs were refractory to mitogenic stimuli, and we found that key proliferation pathways including β-catenin and Yes-associated protein 1 (YAP1) were repressed. This proliferative barrier imposed by fatty acid metabolism in hCOs could be rescued by simultaneous activation of both β-catenin and YAP1 using genetic approaches or a small molecule activating both pathways. These studies highlight that human organoids coupled with higher-throughput screening platforms have the potential to rapidly expand our knowledge of human biology and potentially unlock therapeutic strategies. PMID: 28916735 [PubMed - as supplied by publisher]

Related Articles Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers. Ophthalmology. 2017 Aug 31;: Authors: Laíns I, Kelly RS, Miller JB, Silva R, Vavvas DG, Kim IK, Murta JN, Lasky-Su J, Miller JW, Husain D Abstract PURPOSE: To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). DESIGN: Cross-sectional observational study. PARTICIPANTS: We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. METHODS: All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. MAIN OUTCOME MEASURES: The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. RESULTS: We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10(-9)) among these metabolites. CONCLUSIONS: Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease. PMID: 28916333 [PubMed - as supplied by publisher]

Related Articles Derivatization enhanced separation and sensitivity of long chain-free fatty acids: Application to asthma using targeted and non-targeted liquid chromatography-mass spectrometry approach. Anal Chim Acta. 2017 Oct 09;989:59-70 Authors: Bian X, Sun B, Zheng P, Li N, Wu JL Abstract Long chain-free fatty acids (LCFFAs) play pivotal roles in various physiological functions, like inflammation, insulin resistance, hypertension, immune cell behavior and other biological activities. However, the detection is obstructed by the low contents, structural diversity, high structural similarity, and matrix interference. Herein, a fast cholamine-derivatization, within 1 min at room temperature, coupled with liquid chromatography-mass spectrometry (LC-MS) approach was developed to determine LCFFAs in complex samples. After derivatization, the ionization and separation efficiency were significantly improved, which resulted in up to 2000-fold increase of sensitivity compared with non-derivatization method, and the limits of detection were at low femtogram level. As well, this approach was applied successfully in the rapid profiling or quantification of targeted and non-targeted LCFFAs in the sera of healthy human and asthma patients. The targeted metabolomics method showed that the contents of 17 PUFAs were significantly changed in asthma patients, especially hydroxyeicosatetraenoic acids (HETEs), hydroperoxyeicosatetraenoic acid (HPETEs) and prostaglandins (PGs). The non-targeted method resulted in the tentatively identification of 35 LCFFAs including 31 saturated and mono-unsaturated LCFFAs, and 4 bile acids, except for 27 poly-unsaturated fatty acids (PUFAs), and the multivariate analysis indicated that eicosapentaenoic acid (EPA), ursodeoxycholic acid, deoxycholic acid, isodeoxycholic acid, palmitic acid, 2-lauroleic acid and lauric acid also have significant difference between healthy and asthma groups except for 17 PUFAs. To the best of our knowledge, this is the first report on the relationship of asthma with 5(S)-, 15(S)-HPETE, 8(S)-, 11(S)-HETE, 15(S)-HEPE, PGA2, PGB2, PGE1, PGF1α, PGJ2, and 13, 14-dehydro-15-keto PGF2α (DK-PGF2α). PMID: 28915943 [PubMed - in process]

Related Articles Development of a validated LC- MS/MS method for the quantification of 19 endogenous asthma/COPD potential urinary biomarkers. Anal Chim Acta. 2017 Oct 09;989:45-58 Authors: Khamis MM, Adamko DJ, El-Aneed A Abstract Obstructive airways inflammatory diseases sometimes show overlapping symptoms that hinder their early and correct diagnosis. Current clinical tests are tedious and are of inadequate specificity in special population such as the elderly and children. Therefore, we are developing tandem mass spectrometric (MS/MS) methods for targeted analysis of urine biomarkers. Recently, proton-nuclear magnetic resonance ((1)H-NMR) analysis proposed 50 urinary metabolites as potential diagnostic biomarkers among asthma and chronic obstructive pulmonary disease (COPD) patients. Metabolites are divided into 3 groups based on chemical nature. For group 1 (amines and phenols, 19 urinary metabolites), we developed and validated a high performance liquid chromatographic (HPLC)-MS/MS method using differential isotope labeling (DIL) with dansyl chloride. Method development included the optimization of the derivatization reaction, the MS/MS conditions, and the chromatographic separation. Linearity varied from 2 to 4800 ng/mL and the use of (13)C2-labeled derivatives allowed for the correction of matrix effects as well as the unambiguous confirmation of the identity of each metabolite in the presence of interfering isomers in urine. Despite the challenges associated with method validation, the method was fully validated as per the food and drug administration (FDA) and the European medicines agency (EMA) recommendations. Validation criteria included linearity, precision, accuracy, dilution integrity, selectivity, carryover, and stability. Challenges in selectivity experiments included the isotopic contributions of the analyte towards its internal standard (IS), that was addressed via the optimization of the IS concentration. In addition, incurred sample analysis was performed to ensure that results from patient samples are accurate and reliable. The method was robust and reproducible and is currently being applied in a cohort of asthma and COPD patient urine samples for biomarker discovery purposes. PMID: 28915942 [PubMed - in process]

Related Articles Development and clinical application of radiomics in lung cancer. Radiat Oncol. 2017 Sep 15;12(1):154 Authors: Chen B, Zhang R, Gan Y, Yang L, Li W Abstract Since the discovery of X-rays at the end of the 19(th) century, medical imageology has progressed for 100 years, and medical imaging has become an important auxiliary tool for clinical diagnosis. With the launch of the human genome project (HGP) and the development of various high-throughput detection techniques, disease exploration in the post-genome era has extended beyond investigations of structural changes to in-depth analyses of molecular abnormalities in tissues, organs and cells, on the basis of gene expression and epigenetics. These techniques have given rise to genomics, proteomics, metabolomics and other systems biology subspecialties, including radiogenomics. Radiogenomics is an important revolution in the traditional visually identifiable imaging technology and constitutes a new branch, radiomics. Radiomics is aimed at extracting quantitative imaging features automatically and developing models to predict lesion phenotypes in a non-invasive manner. Here, we summarize the advent and development of radiomics, the basic process and challenges in clinical practice, with a focus on applications in pulmonary nodule evaluations, including diagnostics, pathological and molecular classifications, treatment response assessments and prognostic predictions, especially in radiotherapy. PMID: 28915902 [PubMed - in process]

Related Articles Rapid transcriptional and metabolic regulation of the deacclimation process in cold acclimated Arabidopsis thaliana. BMC Genomics. 2017 Sep 16;18(1):731 Authors: Pagter M, Alpers J, Erban A, Kopka J, Zuther E, Hincha DK Abstract BACKGROUND: During low temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. This is accompanied by dampened oscillations of circadian clock genes and disrupted oscillations of output genes and metabolites. During deacclimation in response to warm temperatures, cold acclimated plants lose freezing tolerance and resume growth and development. While considerable effort has been directed toward understanding the molecular and metabolic basis of cold acclimation, much less information is available about the regulation of deacclimation. RESULTS: We report metabolic (gas chromatography-mass spectrometry) and transcriptional (microarrays, quantitative RT-PCR) responses underlying deacclimation during the first 24 h after a shift of Arabidopsis thaliana (Columbia-0) plants cold acclimated at 4 °C back to warm temperature (20 °C). The data reveal a faster response of the transcriptome than of the metabolome and provide evidence for tightly regulated temporal responses at both levels. Metabolically, deacclimation is associated with decreasing contents of sugars, amino acids, glycolytic and TCA cycle intermediates, indicating an increased need for carbon sources and respiratory energy production for the activation of growth. The early phase of deacclimation also involves extensive down-regulation of protein synthesis and changes in the metabolism of lipids and cell wall components. Hormonal regulation appears particularly important during deacclimation, with extensive changes in the expression of genes related to auxin, gibberellin, brassinosteroid, jasmonate and ethylene metabolism. Members of several transcription factor families that control fundamental aspects of morphogenesis and development are significantly regulated during deacclimation, emphasizing that loss of freezing tolerance and growth resumption are transcriptionally highly interrelated processes. Expression patterns of some clock oscillator components resembled those under warm conditions, indicating at least partial re-activation of the circadian clock during deacclimation. CONCLUSIONS: This study provides the first combined metabolomic and transcriptomic analysis of the regulation of deacclimation in cold acclimated plants. The data indicate cascades of rapidly regulated genes and metabolites that underlie the developmental switch resulting in reduced freezing tolerance and the resumption of growth. They constitute a large-scale dataset of genes, metabolites and pathways that are crucial during the initial phase of deacclimation. The data will be an important reference for further analyses of this and other important but under-researched stress deacclimation processes. PMID: 28915789 [PubMed - in process]

Related Articles Revealing anti-inflammation mechanism of water-extract and oil of forsythiae fructus on carrageenan-Induced edema rats by serum metabolomics. Biomed Pharmacother. 2017 Sep 11;95:929-937 Authors: Yuan A, Gong L, Luo L, Dang J, Gong X, Zhao M, Li Y, Li Y, Peng C Abstract Forsythiae Fructus is an important Chinese medicine which shows a significant effect against inflammation. This study aimed to investigate the preventive anti-inflammation mechanism of Forsythiae Fructus by serum metabolomics strategy and compare the difference of the metabolism pathways between Forsythia extract and Forsythia oil in rat. Four groups (control group, model group, Forsythia extract group and Forsythia oil group) were orally administered 10mL/kg 0.5% Tween 80 solution, 10mL/kg 0.5% Tween 80 solution, 5g/kg Forsythia extract and 0.48mL/kg Forsythia oil respectively. 30min after drug administration, rat acute inflammation was induced by subcutaneous injection of carrageenan in the right paw in model group, Forsythia extract group and Forsythia oil group. After being administered Forsythia extract and Forsythia oil, the percentage of rat paw edema was significantly decreased (P<0.05) compared with model group. Metabolomics based on UPLC-Q-TOF-MS/MS was used to analyze the collected serum sample. Multivariate analysis was established for metabolomics analysis. According to Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) results, four groups were clearly separated. And thirteen alterative biomarkers were identified in the serum, namely PC (19:0/0:0), LysoPC (20:0), LysoPC (20:1), LysoPC (17:0), Sphingosine, Linoleic acid, 3R-hydroxy-butanoic acid (3-HB), 2-hydroxyhexadecanoic acid, Lactic acid, L-Threonine, L-Leucine, Maleic acid, Adipic acid. The change of biomarkers suggested that Forsythia extract affected Linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, Sphingolipid metabolism and Glycerophospholipid metabolism. Forsythia oil affected Sphingolipid metabolism and Glycerophospholipid metabolism. It indicated that Forsythia extract and Forsythia oil both showed significant preventive anti-inflammatory effect through acting on different metabolism pathways. Moreover, efficacy mechanism of Forsythiae Fructus could recover metabolites disturb in the body through affecting particular drug targets associated with the inflammatory pathway. PMID: 28915534 [PubMed - as supplied by publisher]

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Related Articles Investigation of the effects of storage and freezing on mixes of heavy-labeled metabolite and amino acid standards. Rapid Commun Mass Spectrom. 2017 Sep 14;: Authors: Culp-Hill R, Reisz JA, Hansen KC, D'Alessandro A Abstract RATIONALE: High-throughput metabolomics has now made it possible for small/medium-sized laboratories to analyze thousands of samples/year from the most diverse biological matrices including biofluids, cell and tissue extracts. In large scale metabolomics studies, stable isotope-labeled standards are increasingly used to normalize for matrix effects and control for technical reproducibility (e.g. extraction efficiency, chromatographic retention times and mass spectrometry signal stability). However, it is currently unknown how stable mixes of commercially-available standards are following repeated freeze/thaw cycles or prolonged storage of aliquots. METHODS: Standard mixes for (13) C, (15) N or deuterated isotopologues of amino acids and key metabolites from the central carbon and nitrogen pathways (e.g. glycolysis, Krebs cycle, redox homeostasis, purines) were either repeatedly frozen/thawed for up to 10 cycles, or diluted into aliquots prior to frozen storage for up to 42 days. Samples were characterized by ultra-high pressure liquid chromatography-mass spectrometry to determine the stability of the aliquoted standards upon freezing/thawing or prolonged storage. RESULTS: Metabolite standards were stable over up to 10 freeze/thaw cycles, with the exception of adenosine and glutathione, showing technical variability across aliquots in a freeze/thaw-cycle-independent fashion. Storage for up to 42 days of mixes of commercially available standards did not significantly affect the stability of amino acid or metabolite standards for the first two weeks, while progressive degradation (statistically-significant for fumarate ) was observed after three weeks. CONCLUSIONS: Refrigerated or frozen preservation for at least 2 weeks of aliquoted heavy-labeled standard mixes for metabolomics analysis is a feasible and time-/resource-saving strategy for standard metabolomics laboratories. PMID: 28910859 [PubMed - as supplied by publisher]

Related Articles p53-mediated regulation of bile acid disposition attenuates cholic acid-induced cholestasis in mice. Br J Pharmacol. 2017 Sep 14;: Authors: Chen P, Li D, Chen Y, Sun J, Fu K, Guan L, Zhang H, Jiang Y, Li X, Zeng X, Chen X, Huang M, Bi H Abstract BACKGROUND AND PURPOSE: Tumor suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have emerged on discovering its functions in metabolic diseases. Here we investigated the role of p53 in the regulation bile acid disposition and cholestasis. EXPERIMENTAL APPROACH: Bile acid disposition related gene expression profile altered by p53 activation was assessed in mouse primary hepatocytes with p53 depletion and in Trp53-null mice. Dual luciferase reporter assay was used to detect the transcriptional activities of target genes. Anticholestatic effects of p53 activator doxorubicin (Dox) were investigated in a 0.5% cholic acid (CA)-fed mouse model of cholestasis. The changes of bile acids were analyzed using metabolomics analysis. KEY RESULTS: Dox-mediated p53 activation induced Cyp2b10, Sult2a1 and Abcc2/3/4 expression of mice in vitro and in vivo. ABCC3 and CYP2B6 (human ortholog of Cyp2b10) were identified as direct p53 target genes. Dox attenuated CA-induced cholestasis in mice, as demonstrated by shrunken gallbladder size, decreased serum total bile acid and total bilirubin levels and ALP activity. Targeted metabolomics analysis revealed that Dox enhanced the excretion of bile acid metabolites from serum and liver to intestine and feces. Upregulation of Cyp2b10, Sult2a1 and Abcc2/3/4 expression was further confirmed in cholestastic mice. p53 deficiency aggregated CA -induced cholestatic injury in mice and bile acid abundance was decreased in intestine and feces. CONCLUSION AND IMPLICATIONS: Our findings suggest a novel role of p53 in promoting bile acid disposition and alleviating cholestastic syndrome, which provides a potential therapeutic target for cholestasis. PMID: 28910492 [PubMed - as supplied by publisher]

Related Articles Correction: Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study. PLoS Genet. 2017 Sep;13(9):e1007002 Authors: Nowak C, Salihovic S, Ganna A, Brandmaier S, Tukiainen T, Broeckling CD, Magnusson PK, Prenni JE, Wang-Sattler R, Peters A, Strauch K, Meitinger T, Giedraitis V, Ärnlöv J, Berne C, Gieger C, Ripatti S, Lind L, Pedersen NL, Sundström J, Ingelsson E, Fall T Abstract [This corrects the article DOI: 10.1371/journal.pgen.1006379.]. PMID: 28910285 [PubMed - in process]

Related Articles The aetiology of cardiovascular disease: a role for mitochondrial DNA? Cardiovasc J Afr. 2017 Aug 25;28:1-12 Authors: Venter M, van der Westhuizen FH, Elson JL Abstract Cardiovascular disease (CVD) is a world-wide cause of mortality in humans and its incidence is on the rise in Africa. In this review, we discuss the putative role of mitochondrial dysfunction in the aetiology of CVD and consequently identify mitochondrial DNA (mtDNA) variation as a viable genetic risk factor to be considered. We then describe the contribution and pitfalls of several current approaches used when investigating mtDNA in relation to complex disease. We also propose an alternative approach, the adjusted mutational load hypothesis, which would have greater statistical power with cohorts of moderate size, and is less likely to be affected by population stratification. We therefore address some of the shortcomings of the current haplogroup association approach. Finally, we discuss the unique challenges faced by studies done on African populations, and recommend the most viable methods to use when investigating mtDNA variation in CVD and other common complex disease. PMID: 28906532 [PubMed - as supplied by publisher]

Related Articles Benefits and Limitations of DNA Barcoding and Metabarcoding in Herbal Product Authentication. Phytochem Anal. 2017 Sep 14;: Authors: Raclariu AC, Heinrich M, Ichim MC, de Boer H Abstract INTRODUCTION: Herbal medicines play an important role globally in the health care sector and in industrialised countries they are often considered as an alternative to mono-substance medicines. Current quality and authentication assessment methods rely mainly on morphology and analytical phytochemistry-based methods detailed in pharmacopoeias. Herbal products however are often highly processed with numerous ingredients, and even if these analytical methods are accurate for quality control of specific lead or marker compounds, they are of limited suitability for the authentication of biological ingredients. OBJECTIVE: To review the benefits and limitations of DNA barcoding and metabarcoding in complementing current herbal product authentication. METHOD: Recent literature relating to DNA based authentication of medicinal plants, herbal medicines and products are summarised to provide a basic understanding of how DNA barcoding and metabarcoding can be applied to this field. RESULTS: Different methods of quality control and authentication have varying resolution and usefulness along the value chain of these products. DNA barcoding can be used for authenticating products based on single herbal ingredients and DNA metabarcoding for assessment of species diversity in processed products, and both methods should be used in combination with appropriate hyphenated chemical methods for quality control. CONCLUSIONS: DNA barcoding and metabarcoding have potential in the context of quality control of both well and poorly regulated supply systems. Standardisation of protocols for DNA barcoding and DNA sequence-based identification are necessary before DNA-based biological methods can be implemented as routine analytical approaches and approved by the competent authorities for use in regulated procedures. Copyright © 2017 John Wiley & Sons, Ltd. PMID: 28906059 [PubMed - as supplied by publisher]

Related Articles Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women. Am J Clin Nutr. 2017 Sep 13;: Authors: Savolainen O, Lind MV, Bergström G, Fagerberg B, Sandberg AS, Ross A Abstract Background: Diet is frequently associated with both the development and prevention of type 2 diabetes (T2D), but there is a lack of objective tools for assessing the relation between diet and T2D. Biomarkers of dietary intake are unconfounded by recall and reporting bias, and using multiple dietary biomarkers could help strengthen the link between a healthy diet and the prevention of T2D.Objective: The objective of this study was to explore how diet is related to glucose tolerance status (GTS) and to future development of T2D irrespective of common T2D and cardiovascular disease risk factors by using multiple dietary biomarkers.Design: Dietary biomarkers were measured in plasma from 64-y-old Swedish women with different GTS [normal glucose tolerance (NGT; n = 190), impaired glucose tolerance (IGT; n = 209), and diabetes (n = 230)]. The same subjects were followed up after 5 y to determine changes in glucose tolerance (n = 167 for NGT, n = 174 for IGT, and n = 159 for diabetes). ANCOVA and logistic regression were used to explore baseline data for associations between dietary biomarkers, GTS, and new T2D cases at follow-up (n = 69).Results: Of the 10 dietary biomarkers analyzed, β-alanine (beef) (P-raw < 0.001), alkylresorcinols C17 and C19 (whole-grain wheat and rye) (P-raw = 0.003 and 0.011), eicosapentaenoic acid (fish) (P-raw = 0.041), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (fish) (P-raw = 0.002), linoleic acid (P-raw < 0.001), oleic acid (P-raw = 0.003), and α-tocopherol (margarine and vegetable oil) (P-raw < 0.001) were associated with GTS, and CMPF (fish) (OR: 0.72; 95% CI: 0.56, 0.93; P-raw = 0.013) and α-tocopherol (OR: 0.71; 95% CI: 0.51, 0.98; P-raw = 0.041) were inversely associated with future T2D development.Conclusions: Several circulating dietary biomarkers were strongly associated with GTS after correction for known T2D risk factors, underlining the role of diet in the development and prevention of T2D. To our knowledge, this study is the first to use multiple dietary biomarkers to investigate the link between diet and disease risk. PMID: 28903960 [PubMed - as supplied by publisher]

Related Articles Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon. Cancer Res. 2017 Jun 15;77(12):3352-3363 Authors: Dermadi D, Valo S, Ollila S, Soliymani R, Sipari N, Pussila M, Sarantaus L, Linden J, Baumann M, Nyström M Abstract Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase risks of colorectal cancer. Here, we performed a long-term diet study in mice to follow tumorigenesis and characterize structural and metabolic changes in colon mucosa associated with WD and predisposition to colorectal cancer. WD increased colon tumor numbers, and mucosa proteomic analysis indicated severe deregulation of intracellular bile acid (BA) homeostasis and activation of cell proliferation. WD also increased crypt depth and colon cell proliferation. Despite increased luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA transporters FABP6, OSTβ, and ASBT and decreased concentrations of secondary BA deoxycholic acid and lithocholic acid, indicating reduced activity of the nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer risk by FXR inactivation, leading to BA deregulation and increased colon cell proliferation. Cancer Res; 77(12); 3352-63. ©2017 AACR. PMID: 28416481 [PubMed - indexed for MEDLINE]

Related Articles Impact of Maillard Reaction products on Nutrition and Health: Current knowledge and need to understand their fate in the human digestive system. Crit Rev Food Sci Nutr. 2017 Sep 13;:0 Authors: ALJahdali N, Carbonero F Abstract The Maillard Reaction (MR) is a non-enzymatic chemical reaction which results in the linkage between the amino group of amino acids and the carbonyl group of reduced sugars. MR products (MRPs) are common components of processed foods, mainly as a result of heating, especially in the Western diet. MRPs are classified as into three stages: initial, intermediate, and final stages, indicative of increased complexity and size, incurring different flavor, aroma, and texture. MRPs presence is known to reduce the nutritional quality of foods, particularly by reducing protein digestibility. Early reports have linked MRPs, especially advanced glycation end-products (AGEs) present in high concentration in the typical Western diet, to health conditions and diseases. However conflicting data has since been reported, and only a few (acrylamide, heterocyclic amines and 5-Hydroxymethylfurfural) MRPs have documented potential toxic or carcinogenic effects. High molecular weight MRPs are not available for direct absorption in the higher gastrointestinal tract, and are thus mostly metabolized by resident colonic microbes. MRPs have been the subject of sparse research interest in comparison with other non-digestible dietary elements. In this review, we outline the state of knowledge on MRPs in nutrition and health, and highlight the need to develop the limited knowledge on their impact on the gut microbiota and which metabolites derive from MRPs fermentation. PMID: 28901784 [PubMed - as supplied by publisher]

Related Articles UPLC‑QTOFMS‑based metabolomic analysis of the serum of hypoxic preconditioning mice. Mol Med Rep. 2017 Sep 13;: Authors: Liu J, Zhan G, Chen D, Chen J, Yuan ZB, Zhang EL, Gao YX, Xu G, Sun BD, Liao W, Gao YQ Abstract Hypoxic preconditioning (HPC) is well‑known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC. PMID: 28901489 [PubMed - as supplied by publisher]

Related Articles Comparative study on microsampling techniques in metabolic fingerprinting studies applying gas chromatography-MS analysis. Bioanalysis. 2017 Sep 13;: Authors: Cala MP, Meesters RJ Abstract AIM: Sample collection and preparation are important steps in the metabolomics workflow. Any improvement should be aimed toward making them simpler, faster and more reproducible. This paper describes the evaluation of different types of whole blood microsampling techniques applied in a metabolic fingerprinting study of breast cancer patients. RESULTS: A total of 139, 124 and 128 metabolites were identified in protein precipitation, dried matrix on paper discs and Mitra(®) volumetric absorptive microsampling, respectively in 80% of the sample sets, where the quality control samples had a relative standard deviation of <30%. Ten metabolites in breast cancer samples were detected as being altered significantly (p < 0.05). CONCLUSION: Our results suggest that whole blood microsampling techniques do not obtain statistically different results in comparison with the metabolomics applied standard reference method of protein precipitation, in terms of the number of detected compounds, the reproducibility and modeling of differences between the groups. PMID: 28901168 [PubMed - as supplied by publisher]

Related Articles Serum and Brain Metabolomic Variations Reveal Perturbation of Sleep Deprivation on Rats and Ameliorate Effect of Total Ginsenoside Treatment. Int J Genomics. 2017;2017:5179271 Authors: Gou XJ, Cen F, Fan ZQ, Xu Y, Shen HY, Zhou MM Abstract Sleep loss or sleep deprivation (SD) refers to shorter sleep than average baseline need, and SD has been a serious problem of modern societies which affects health and well-being. Panax ginseng is a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that total ginsenosides (GS), the extracts from Panax ginseng, could effectively improve cognition and behavior on SD rats. However, little is known about its metabolomic study. In this study, serum and brain metabolomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to evaluate the efficacy and study the mechanism of GS on a rat model of SD. With pattern recognition analysis of serum and brain tissue metabolite profile, a clear separation of the model group and control group was acquired for serum and brain tissue samples; the MGS (model + GS) group showed a tendency of recovering when compared to control group, which was consistent with behavioral and biochemical parameters. 39 and 40 potential biomarkers of brain tissues and serum samples, respectively, were identified and employed to explore the possible mechanism. Our work revealed that GS has significant protective effects on SD, and metabolomics is a useful tool for evaluating efficacy and elucidating mechanism in TCM. PMID: 28900617 [PubMed]