PubMed
Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers?
Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers?
PLoS One. 2017;12(7):e0177738
Authors: Savolainen O, Fagerberg B, Vendelbo Lind M, Sandberg AS, Ross AB, Bergström G
Abstract
AIM: The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers.
METHODS: Gas chromatography-tandem mass spectrometry metabolomics was used in a nested case-control study based on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years follow-up. The metabolomics results were used as a standalone prediction model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D.
RESULTS: Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738-0.850]) and 0.808 [0.749-0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having a lower predictive power (0.657 [0.577-0.736]). Prediction based on non-blood based measures was 0.638 [0.565-0.711]).
CONCLUSIONS: Established measures of T2D risk remain the best predictor of T2D risk in this population. Additional markers detected using metabolomics are likely related to these measures as they did not enhance the overall prediction in a combined model.
PMID: 28692646 [PubMed - in process]
Comparison of fully-wettable RPLC stationary phases for LC-MS-based cellular metabolomics.
Comparison of fully-wettable RPLC stationary phases for LC-MS-based cellular metabolomics.
Electrophoresis. 2017 Jul 10;:
Authors: Si-Hung L, Causon TJ, Hann S
Abstract
Reversed-phase LC combined with high-resolution mass spectrometry (HRMS) is one of the most popular methods for cellular metabolomics studies. Due to the difficulties in analysing a wide range of polarities encountered in the metabolome, 100%-wettable reversed-phase materials are frequently used to maximise metabolome coverage within a single analysis. Packed with silica-based sub-3 μm diameter particles, these columns allow high separation efficiency and offer a reasonable compromise for metabolome coverage within a single analysis. While direct performance comparison can be made using classical chromatographic characterisation approaches, a comprehensive assessment of the column's performance for cellular metabolomics requires use of a full LC-HRMS workflow in order to reflect realistic study conditions used for cellular metabolomics. In this study, a comparison of several reversed-phase LC columns for metabolome analysis using such a dedicated workflow is presented. All columns were tested under the same analytical conditions on an LC-Time-of-Flight-MS (LC-TOFMS) platform using a variety of authentic metabolite standards and biotechnologically-relevant yeast cell extracts. Data on total workflow performance including retention behaviour, peak capacity, coverage, and molecular feature extraction repeatability from these columns are presented with consideration for both non-targeted screening and differential metabolomics workflows using authentic standards and Pichia pastoris cell extract samples. This article is protected by copyright. All rights reserved.
PMID: 28691762 [PubMed - as supplied by publisher]
Nuclear magnetic resonance- and mass spectometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats.
Nuclear magnetic resonance- and mass spectometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats.
J Appl Toxicol. 2017 Jul 10;:
Authors: Wu C, Chen CH, Chen HC, Liang HJ, Chen ST, Lin WY, Wu KY, Chiang SY, Lin CY
Abstract
Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using (1) H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg(-1) ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F2α ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity.
PMID: 28691739 [PubMed - as supplied by publisher]
Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs.
Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs.
Anal Bioanal Chem. 2017 Jul 10;:
Authors: Shu Y, Liu Z, Zhao S, Song Z, He D, Wang M, Zeng H, Lu C, Lu A, Liu Y
Abstract
Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic fashion with the synergistic function of multiple characteristic constituents. The holism philosophy of TCM is coincident with global and systematic theories of metabolomics. The proposed pseudotargeted metabolomics methodologies were employed for the establishment of reliable quality control markers for use in the screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages of both targeted and untargeted methods. In the present study, targeted metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for in vivo quantitative plasma pharmacochemistry study of characteristic prototypic constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS with better specificity and selectivity was employed for identification of untargeted metabolites in the complex plasma matrix. In all, 32 prototypic metabolites were quantitatively determined, and 66 biotransformed metabolites were convincingly identified after being orally administered with standard extracts of four labeled Citrus TCMs. The global absorption and metabolism process of complex TCMs was depicted in a systematic manner.
PMID: 28691151 [PubMed - as supplied by publisher]
Comparison of Salt Tolerance in Soja Based on Metabolomics of Seedling Roots.
Comparison of Salt Tolerance in Soja Based on Metabolomics of Seedling Roots.
Front Plant Sci. 2017;8:1101
Authors: Li M, Guo R, Jiao Y, Jin X, Zhang H, Shi L
Abstract
Soybean is an important economic crop that is continually threatened by abiotic stresses, especially salt stress. Wild soybean is an important germplasm resource for the breeding of cultivated soybean. The root system plays a very important role in plant salt tolerance. To explore the salt tolerance-related mechanisms among Soja, we have demonstrated the seedling roots' growth and metabolomics in wild soybean, semi-wild soybean, and cultivated soybean under two types of salt stress by using gas chromatography-mass spectrometry. We characterized 47 kinds of differential metabolites under neutral salt stress, and isoleucine, serine, l-allothreonine, glutamic acid, phenylalanine, asparagines, aspartic acid, pentadecanoic acid, lignoceric acid, oleic acid, galactose, tagatose, d-arabitol, dihydroxyacetone, 3-hydroxybutyric acid, and glucuronic acid increased significantly in the roots of wild soybean seedlings. However, these metabolites were suppressed in semi-wild and cultivated soybeans. Amino acid, fatty acid, sugars, and organic acid synthesis and the secondary metabolism of antioxidants increased significantly in the roots of wild soybean seedling. Under alkaline salt stress, wild soybean contained significantly higher amounts of proline, glutamic acid, aspartic acid, l-allothreonine, isoleucine, serine, alanine, arachidic acid, oleic acid, cis-gondoic acid, fumaric acid, l-malic acid, citric acid, malonic acid, gluconic acid, 5-methoxytryptamine, salicylic acid, and fluorene than semi-wild and cultivated soybeans. Our study demonstrated that carbon and nitrogen metabolism, and the tricarboxylic acid (TCA) cycle and receiver operating characteristics (especially the metabolism of phenolic substances) of the seedling roots were important to resisting salt stress and showed a regular decreasing trend from wild soybean to cultivated soybean. The metabolomics's changes were critical factors in the evolution of salt tolerance among Soja. This study provides new insights into salt tolerance in soybean, and presents quantitative parameters for a salt tolerant soybean breeding system, which is conducive to the rational use and protection of wild soybean resources.
PMID: 28690628 [PubMed - in process]
Metabolite profiling in early clinical drug development: Current status and future prospects.
Metabolite profiling in early clinical drug development: Current status and future prospects.
Expert Opin Drug Metab Toxicol. 2017 Jul 10;:
Authors: Ufer M, Juif PE, Boof ML, Muehlan C, Dingemanse J
PMID: 28689432 [PubMed - as supplied by publisher]
Factors affecting separation and detection of bile acids by liquid chromatography coupled with mass spectrometry in negative mode.
Factors affecting separation and detection of bile acids by liquid chromatography coupled with mass spectrometry in negative mode.
Anal Bioanal Chem. 2017 Jul 08;:
Authors: Yin S, Su M, Xie G, Li X, Wei R, Liu C, Lan K, Jia W
Abstract
Bile acids (BAs) are cholesterol metabolites with important biological functions. They undergo extensive host-gut microbial co-metabolisms during the enterohepatic circulation, creating a vast structural diversity and resulting in great challenges to separate and detect them. Based on the bioanalytical reports in the past decade, this work developed three chromatographic gradient methods to separate a total of 48 BA standards on an ethylene-bridged hybrid (BEH) C18 column and high-strength silica (HSS) T3 column and accordingly unraveled the factors affecting the separation and detection of them by liquid chromatography coupled with mass spectrometry (LC-MS). It was shown that both the acidity and ammonium levels in mobile phases reduced the electrospray ionization (ESI) of BAs as anions of [M-H](-), especially for those unconjugated ones without 12-hydroxylation. It was also found that the retention of taurine conjugates on the BEH C18 column was sensitive to the strength of formic acid and ammonium in mobile phases. By using the volatile buffers with an equivalent ammonium level as mobile phases, we comprehensively demonstrated the effects of the elution pH value on the retention behaviors of BAs on both the BEH C18 column and HSS T3 column. Based on the retention data acquired on a C18 column, we presented the ionization constants (pK a) of various BAs with the widest coverage beyond those of previous reports. When we made attempts to establish the structure-retention relationships (SRRs) of BAs, the lack of discriminative structural descriptors for BA stereoisomers emerged as the bottleneck problem. The methods and results presented in this work are especially useful for the development of reliable, sensitive, high-throughput, and robust LC-MS bioanalytical protocols for the quantitative metabolomic studies. Graphical Abstract Nonlinear curve fitting of capacity factors and elution pH value for the separation of common unconjugated bile acids.
PMID: 28689325 [PubMed - as supplied by publisher]
Metabolic signature for severe cirrhosis with inflammation or hepatic encephalopathy: do we really face two different entities?
Metabolic signature for severe cirrhosis with inflammation or hepatic encephalopathy: do we really face two different entities?
J Hepatol. 2017 Jul 05;:
Authors: Weiss N, Colsch B, Fenaille F, Junot C, Thabut D
PMID: 28688802 [PubMed - as supplied by publisher]
Preparation and evaluation of mesoporous silica layers on radially elongated pillars.
Preparation and evaluation of mesoporous silica layers on radially elongated pillars.
J Chromatogr A. 2017 Jun 24;:
Authors: Futagami S, Hara T, Ottevaere H, Baron GV, Desmet G, De Malsche W
Abstract
The present paper describes the application of a sol-gel procedure on radially elongated pillars (REPs) using tetramethoxysilane and methyltrimethoxysilane. After octadecylsilylation, the quality of the porous layered REP (PLREP) columns was evaluated by in-situ determination of migration velocities and band broadening of coumarin dyes with fluorescence microscopy in reversed-phase liquid chromatography. Based on the increase in retention due to the sol-gel process, an increase in accessible specific surface by a factor of 112 was observed. Argon physisorption measurements on bulk monoliths prepared with the same method revealed a predominant pore size of 91Å. Plate heights as low as 0.4-0.8μm (k=0-1.97) could be obtained thanks to the very low dispersion of the REP format and to the fact that the applied silica layer was conformally and uniformly deposited on the flow-through channels. A kinetic plot analysis demonstrated that the studied PLREP column will deliver more theoretical plates per unit of time than a 5μm core shell packed bed when more than 1.0×10(4) theoretical plates are required.
PMID: 28688720 [PubMed - as supplied by publisher]
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Comparative toxicity of chloro- and bromo-nitromethanes in mice based on a metabolomic method.
Comparative toxicity of chloro- and bromo-nitromethanes in mice based on a metabolomic method.
Chemosphere. 2017 Jun 29;185:20-28
Authors: Yin J, Wu B, Zhang XX, Xian Q
Abstract
Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts have been widely found in drinking water. In vitro test found HNMs could induce higher cytotoxicity and genotoxicity than trihalomethanes and haloacetic acids. However, data on toxic effect from in vivo experiment is limited. In this study, bromonitromethane (BNM), bromochloronitromethane (BCNM) and trichloronitromethane (TCNM) were chosen as target HNMs, and exposed to mice for 30 d. Hepatic toxicity and serum metabolic profiles were determined to reveal toxic effects and mechanisms of the three HNMs. Results showed the three HNMs significantly decreased relative liver weight, indicating liver is one of the target organs. Further, the three HNMs exposure damaged hepatic antioxidant defense system, and increased oxidative DNA damage. Nuclear magnetic resonance based metabolomics analysis found amino acid metabolism and carbohydrate metabolism were disturbed by HNMs exposure. Some metabolites in these metabolisms are related to oxidative stress and damage. Combined with above results, BNM had the highest toxicity, followed by BCNM and TCNM, indicating bromo-HNMs had higher toxicity than chloro-HNMs. Induction of oxidative stress is one of the toxicity mechanisms of HNMs. This study firstly provides the insight into in vivo toxicity of HNMs and their underlying mechanisms based on metabolomics methods, which is very useful for their health risk assessment in drinking water.
PMID: 28683333 [PubMed - as supplied by publisher]
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.
Cell Metab. 2017 Jul 05;26(1):212-229.e12
Authors: Martínez-Sánchez N, Seoane-Collazo P, Contreras C, Varela L, Villarroya J, Rial-Pensado E, Buqué X, Aurrekoetxea I, Delgado TC, Vázquez-Martínez R, González-García I, Roa J, Whittle AJ, Gomez-Santos B, Velagapudi V, Tung YCL, Morgan DA, Voshol PJ, Martínez de Morentin PB, López-González T, Liñares-Pose L, Gonzalez F, Chatterjee K, Sobrino T, Medina-Gómez G, Davis RJ, Casals N, Orešič M, Coll AP, Vidal-Puig A, Mittag J, Tena-Sempere M, Malagón MM, Diéguez C, Martínez-Chantar ML, Aspichueta P, Rahmouni K, Nogueiras R, Sabio G, Villarroya F, López M
Abstract
Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
PMID: 28683288 [PubMed - in process]
Metabolomic Studies of Indonesian Jamu Medicines: Prediction of Jamu Efficacy and Identification of Important Metabolites.
Metabolomic Studies of Indonesian Jamu Medicines: Prediction of Jamu Efficacy and Identification of Important Metabolites.
Mol Inform. 2017 Jul 06;:
Authors: Wijaya SH, Batubara I, Nishioka T, Altaf-Ul-Amin M, Kanaya S
Abstract
In order to obtain a better understanding why some Jamu formulas can be used to treat a specific disease, we performed metabolomic studies of Jamu by taking into consideration the biologically active compounds existing in plants used as Jamu ingredients. A thorough integration of information from omics is expected to provide solid evidence-based scientific rationales for the development of modern phytomedicines. This study focused on prediction of Jamu efficacy based on its component metabolites and also identification of important metabolites related to each efficacy group. Initially, we compared the performance of Support Vector Machines and Random Forest to predict the Jamu efficacy with three different data pre-processing approaches, such as no filtering, Single Filtering algorithm, and a combination of Single Filtering algorithm and feature selection using Regularized Random Forest. Both classifiers performed very well and according to 5-fold cross-validation results, the mean accuracy of Support Vector Machine with linear kernel was slightly better than Random Forest. It can be concluded that machine learning methods can successfully relate Jamu efficacy with metabolites. In addition, we extended our analysis by identifying important metabolites from the Random Forest model. The inTrees framework was used to extract the rules and to select important metabolites for each efficacy group. Overall, we identified 94 significant metabolites associated to 12 efficacy groups and many of them were validated by published literature and KNApSAcK Metabolite Activity database.
PMID: 28682479 [PubMed - as supplied by publisher]
Assessment of the Therapeutic Potential of Persimmon Leaf Extract on Prediabetic Subjects.
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Assessment of the Therapeutic Potential of Persimmon Leaf Extract on Prediabetic Subjects.
Mol Cells. 2017 Jul 06;:
Authors: Khan MM, Tran BQ, Jang YJ, Park SH, Fondrie WE, Chowdhury K, Yoon SH, Goodlett DR, Chae SW, Chae HJ, Seo SY, Goo YA
Abstract
Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.
PMID: 28681595 [PubMed - as supplied by publisher]
Untargeted metabolomics of neuronal cell culture: A model system for the toxicity testing of insecticide chemical exposure.
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Untargeted metabolomics of neuronal cell culture: A model system for the toxicity testing of insecticide chemical exposure.
J Appl Toxicol. 2017 Jul 06;:
Authors: Hayton S, Maker GL, Mullaney I, Trengove RD
Abstract
Toxicity testing is essential for the protection of human health from exposure to toxic environmental chemicals. As traditional toxicity testing is carried out using animal models, mammalian cell culture models are becoming an increasingly attractive alternative to animal testing. Combining the use of mammalian cell culture models with screening-style molecular profiling technologies, such as metabolomics, can uncover previously unknown biochemical bases of toxicity. We have used a mass spectrometry-based untargeted metabolomics approach to characterize for the first time the changes in the metabolome of the B50 cell line, an immortalised rat neuronal cell line, following acute exposure to two known neurotoxic chemicals that are common environmental contaminants; the pyrethroid insecticide permethrin and the organophosphate insecticide malathion. B50 cells were exposed to either the dosing vehicle (methanol) or an acute dose of either permethrin or malathion for 6 and 24 hours. Intracellular metabolites were profiled by gas chromatography-mass spectrometry. Using principal components analysis, we selected the key metabolites whose abundance was altered by chemical exposure. By considering the major fold changes in abundance (>2.0 or <0.5 from control) across these metabolites, we were able to elucidate important cellular events associated with toxic exposure including disrupted energy metabolism and attempted protective mechanisms from excitotoxicity. Our findings illustrate the ability of mammalian cell culture metabolomics to detect finer metabolic effects of acute exposure to known toxic chemicals, and validate the need for further development of this process in the application of trace-level dose and chronic toxicity studies, and toxicity testing of unknown chemicals.
PMID: 28681389 [PubMed - as supplied by publisher]
Simultaneous production of intracellular triacylglycerols and extracellular polyol esters of fatty acids by Rhodotorula babjevae and Rhodotorula aff. paludigena.
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Simultaneous production of intracellular triacylglycerols and extracellular polyol esters of fatty acids by Rhodotorula babjevae and Rhodotorula aff. paludigena.
J Ind Microbiol Biotechnol. 2017 Jul 05;:
Authors: Garay LA, Sitepu IR, Cajka T, Cathcart E, Fiehn O, German JB, Block DE, Boundy-Mills KL
Abstract
Microbial oils have been analyzed as alternatives to petroleum. However, just a handful of microbes have been successfully adapted to produce chemicals that can compete with their petroleum counterparts. One of the reasons behind the low success rate is the overall economic inefficiency of valorizing a single product. This study presents a lab-scale analysis of two yeast species that simultaneously produce multiple high-value bioproducts: intracellular triacylglycerols (TG) and extracellular polyol esters of fatty acids (PEFA), two lipid classes with immediate applications in the biofuels and surfactant industries. At harvest, the yeast strain Rhodotorula aff. paludigena UCDFST 81-84 secreted 20.9 ± 0.2 g L(-1) PEFA and produced 8.8 ± 1.0 g L(-1) TG, while the yeast strain Rhodotorula babjevae UCDFST 04-877 secreted 11.2 ± 1.6 g L(-1) PEFA and 18.5 ± 1.7 g L(-1) TG. The overall glucose conversion was 0.24 and 0.22 g(total lipid) g (glucose)(-1) , respectively. The results present a stable and scalable microbial growth platform yielding multiple co-products.
PMID: 28681129 [PubMed - as supplied by publisher]
Novel immune checkpoint blocker to treat Merkel cell carcinoma.
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Novel immune checkpoint blocker to treat Merkel cell carcinoma.
Oncoimmunology. 2017;6(6):e1315496
Authors: Galluzzi L, Kroemer G
PMID: 28680746 [PubMed - in process]
Plasma acylcarnitines are associated with pulmonary hypertension.
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Plasma acylcarnitines are associated with pulmonary hypertension.
Pulm Circ. 2017 Mar;7(1):211-218
Authors: Luo N, Craig D, Ilkayeva O, Muehlbauer M, Kraus WE, Newgard CB, Shah SH, Rajagopal S
Abstract
Quantifying metabolic derangements in pulmonary hypertension (PH) by plasma metabolomics could identify biomarkers useful for diagnosis and treatment. The objective of this paper is to test the hypotheses that circulating metabolites are differentially expressed in PH patients compared with controls and among different hemodynamic subtypes of PH associated with left heart disease. We studied patients enrolled in the CATHGEN biorepository with PH (right heart catheterization mPAP ≥ 25 mmHg; n = 280). Of these, 133 met criteria for postcapillary PH, 82 for combined precapillary and postcapillary PH (CpcPH), and 65 for precapillary PH. Targeted profiling of 63 metabolites (acylcarnitines, amino acids, and ketones) was performed using tandem flow injection mass spectrometry. Multivariable linear regression was used to determine differences in metabolite factors derived from a principal components analysis between PH cases, PH subtypes, and non-PH controls. In adjusted models, the metabolite factor loaded with long-chain acylcarnitines was higher in all PH cases versus non-PH controls (P = 0.00008), but did not discriminate between CpcPH and postcapillary PH (P = 0.56). In analyses of subtypes, CpcPH patients had lower levels of factors loaded with urea cycle amino acids and short chain acylcarnitines as compared to controls (P = 0.002 and P = 0.01, respectively) and as compared to postcapillary PH (P = 0.04 and P = 0.02, respectively). Compared to controls, PH was strongly associated with greater concentrations of long-chain acylcarnitines. Postcapillary PH and CpcPH were weakly associated with distinct metabolomic profiles. These findings suggest the presence of unique metabolic abnormalities in subtypes of PH and may reflect underlying pathophysiology.
PMID: 28680580 [PubMed - in process]
The Induction of Noble Rot (Botrytis cinerea) Infection during Postharvest Withering Changes the Metabolome of Grapevine Berries (Vitis vinifera L., cv. Garganega).
Related Articles
The Induction of Noble Rot (Botrytis cinerea) Infection during Postharvest Withering Changes the Metabolome of Grapevine Berries (Vitis vinifera L., cv. Garganega).
Front Plant Sci. 2017;8:1002
Authors: Negri S, Lovato A, Boscaini F, Salvetti E, Torriani S, Commisso M, Danzi R, Ugliano M, Polverari A, Tornielli GB, Guzzo F
Abstract
The natural or induced development of noble rot caused by the fungus Botrytis cinerea during the late stages of grapevine (Vitis vinifera L.) berry ripening is used in some traditional viticulture areas to produce high-quality wines such as Sauternes and Tokaji. In this research, we wanted to verify if by changing the environmental conditions during post-harvest withering we could induce the noble rot development on harvested berries in order to positively change the wine produced from withered Garganega berries. Therefore, we exposed the berries to postharvest withering under normal or artificially humid conditions, the latter to induce noble rot. The presence of noble rot symptoms was associated with the development of B. cinerea in the berries maintained under humid conditions. The composition of infected and non-infected berries was investigated by untargeted metabolomics using liquid chromatography/mass spectrometry. We also explored the effects of the two withering methods on the abundance of volatile organic compounds in wine by yeast-inoculated micro-fermentation followed by targeted gas chromatography/mass spectrometry. These experiments revealed significant metabolic differences between berries withered under normal and humid conditions, indicating that noble rot affects berry metabolism and composition. As well as well-known botrytization markers, we detected two novel lipids that have not been observed before in berries infected with noble rot. Unraveling the specific metabolic profile of berries infected with noble rot may help to determine the compounds responsible for the organoleptic quality traits of botrytized Garganega wines.
PMID: 28680428 [PubMed - in process]
IgA N- and O-glycosylation profiling reveals no association with the pregnancy-related improvement in rheumatoid arthritis.
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IgA N- and O-glycosylation profiling reveals no association with the pregnancy-related improvement in rheumatoid arthritis.
Arthritis Res Ther. 2017 Jul 05;19(1):160
Authors: Bondt A, Nicolardi S, Jansen BC, Kuijper TM, Hazes JMW, van der Burgt YEM, Wuhrer M, Dolhain RJEM
Abstract
BACKGROUND: The Fc glycosylation of immunoglobulin G (IgG) is well known to associate with rheumatoid arthritis (RA) disease activity. The same may be true for other classes of Igs. In the present study, we sought to determine whether the glycosylation of IgA was different between healthy subjects and patients with RA, as well as whether it was associated with RA disease activity, in particular with the pregnancy-associated improvement thereof or the flare after delivery.
METHODS: A recently developed high-throughput method for glycoprofiling of IgA1 was applied to affinity-captured IgA from sera of patients with RA (n = 252) and healthy control subjects (n = 32) collected before, during and after pregnancy.
RESULTS: IgA1 O-glycans bore more sialic acids in patients with RA than in control subjects. In addition, levels of bisecting N-acetylglucosamine of the N-glycans at asparagine 144 were higher in the patients with RA. The levels of several N-glycosylation traits were shown to change with pregnancy, similar to what has been shown before for IgG. However, the changes in IgA glycosylation were not associated with improvement or a flare of disease activity.
CONCLUSIONS: The glycosylation of IgA differs between patients with RA and healthy control subjects. However, our data suggest only a minor, if any, association of IgA glycosylation with RA disease activity.
PMID: 28679431 [PubMed - in process]