PubMed

Related Articles Combined use of cutinase and high-resolution mass-spectrometry to query the molecular architecture of cutin. Plant Methods. 2018;14:117 Authors: Bhunia RK, Showman LJ, Jose A, Nikolau BJ Abstract Background: Cutin is a complex, highly cross-linked polyester consisting of hydroxylated and epoxidated acyl lipid monomers. Because of the complexity of the polymer it has been difficult to define the chemical architecture of the polymer, which has further limited the ability to identify the catalytic components that assemble the polymer. Analogous to methods that define the structure of oligosaccharides, we demonstrate a strategy that utilizes cutinase to generate cutin subfragments consisting of up to four monomeric units, whose structure and spatial distribution in the polymer is revealed by high-resolution mass spectrometry. Moreover, the application of mass-spectrometric fragmentation and labelling of the end of the oligomers, one is able to define the order of monomers in the oligomer. The systematic application of this strategy can greatly facilitate understanding the chemical architecture of this complex polymer. Results: The chemical architecture of plant cutin is dissected by coupling an enzymatic system that deconstructs the polymer into subfragments consisting of dimers, trimers and tetramers of cutin monomers, with group-specific labeling and mass spectrometry. These subfragments can be generated with one of over 1200 of cutinases identified from diverse biological sources. The parallel chemical labeling of the polymer with dansyl, alkyl or p-dimethylaminophenacyl reagents can identify the chemical distribution of non-esterified hydroxyl- and carboxyl-groups among the monomers. This combined strategy is applied to cutin isolated from with apple fruit skins, and a combination of gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-quadrupole time-of-flight (Q-TOF) MS is used to determine the order of the monomers in the cutinase-generated subfragments. Finally, we demonstrate the use of matrix-assisted laser desorption-ionization-MS to determine the spatial distribution of the cutinase-generated subfragments. Conclusion: Our experimental results demonstrate an advancement to overcome the current limitations in identifying cutin oligomeric structure and allows one to more efficiently address new biological questions about cutin biosynthesis. We submit that the systematic application of these methods will enable the construction of more accurate architectural models of cutin, which is a prerequisite to identifying cutin-biosynthetic components. PMID: 30603042 [PubMed]

Related Articles Random Forest Analysis of Untargeted Metabolomics Data Suggests Increased Use of Omega Fatty Acid Oxidation Pathway in Drosophila Melanogaster Larvae Fed a Medium Chain Fatty Acid Rich High-Fat Diet. Metabolites. 2018 Dec 31;9(1): Authors: Oza VH, Aicher JK, Reed LK Abstract Obesity is a complex disease, shaped by both genetic and environmental factors such as diet. In this study, we use untargeted metabolomics and Drosophila melanogaster to model how diet and genotype shape the metabolome of obese phenotypes. We used 16 distinct outbred genotypes of Drosophila larvae raised on normal (ND) and high-fat (HFD) diets, to produce three distinct phenotypic classes; genotypes that stored more triglycerides on a ND relative to the HFD, genotypes that stored more triglycerides on a HFD relative to ND, and genotypes that showed no change in triglyceride storage on either of the two diets. Using untargeted metabolomics we characterized 350 metabolites: 270 with definitive chemical IDs and 80 that were chemically unidentified. Using random forests, we determined metabolites that were important in discriminating between the HFD and ND larvae as well as between the triglyceride phenotypic classes. We found that flies fed on a HFD showed evidence of an increased use of omega fatty acid oxidation pathway, an alternative to the more commonly used beta fatty acid oxidation pathway. Additionally, we observed no correlation between the triglyceride storage phenotype and free fatty acid levels (laurate, caprate, caprylate, caproate), indicating that the distinct metabolic profile of fatty acids in high-fat diet fed Drosophila larvae does not propagate into triglyceride storage differences. However, dipeptides did show moderate differences between the phenotypic classes. We fit Gaussian graphical models (GGMs) of the metabolic profiles for HFD and ND flies to characterize changes in metabolic network structure between the two diets, finding the HFD to have a greater number of edges indicating that metabolome varies more across samples on a HFD. Taken together, these results show that, in the context of obesity, metabolomic profiles under distinct dietary conditions may not be reliable predictors of phenotypic outcomes in a genetically diverse population. PMID: 30602659 [PubMed]

Related Articles Metabolic response of longitudinal muscles to acute hypoxia in sea cucumber Apostichopus japonicus (Selenka): A metabolome integrated analysis. Comp Biochem Physiol Part D Genomics Proteomics. 2018 Dec 27;29:235-244 Authors: Li L, Chen M, Storey KB Abstract Hypoxia is a severe problem in aquatic environments worldwide and has caused mass mortality of sea cucumbers (& other species) for decades, seriously affecting the sustainable development of aquaculture. Investigations of the metabolic disruptions and biochemical responses associated with acute hypoxia stress in sea cucumbers can provide a theoretical basis and guidance for improving aquaculture. A metabolomics approach to characterize changes in the profiles of endogenous small molecules in response to acute hypoxia can help to identify the main underlying causes of metabolic damage and potentially suggest solutions to alleviate to improve viability. The current study uses liquid chromatography-mass spectrometry (LC-MS) and multivariate analysis methods to evaluate the metabolic profile of longitudinal muscles from A. japonicus exposed to acute hypoxia stress (by bubbling the aquaria water with nitrogen aeration to decrease dissolved oxygen to 2 mg/L in 2 min) for 6 or 24 h (experimental groups EG6 or EG24) and control group (CG, n = 10, respectively). The results showed that 29 and 62 metabolites were influenced significantly in EG6 and EG24, respectively, mainly including lipids, glycosides and their derivatives. Levels of most lipids (fatty acids, glycerolipids, glycerophospholipids, sphingolipids and sterols) were elevated in both experimental groups, and increased with elongation of hypoxia, implying that the homeostasis of synthesis and degradation of lipids and their derivatives was strongly affected by hypoxia stress. Pathway enrichment analysis was performed to further assess the importance of differential metabolite expression to the development of the A. japonicus response to hypoxia, showing that 4 (fatty acid biosynthesis, d-glutamine and d-glutamate metabolism, glycolysis/gluconeogenesis, glyoxylate and dicarboxylate metabolism) and 2 (steroid biosynthesis, longevity regulating pathway) pathways were markedly enriched in EG6 and EG24, respectively. These results suggested that fatty acid synthesis was strengthened significantly in both treatment groups, and the degree was higher in EG24 than in EG6, providing valuable information towards understanding the special adaptive mechanism of A. japonicus to hypoxia stress. PMID: 30602139 [PubMed - as supplied by publisher]

Related Articles Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival. Cancer. 2019 Jan 02;: Authors: Vantaku V, Donepudi SR, Piyarathna DWB, Sekhar Amara C, Ambati CR, Tang W, Putluri V, Chandrashekar DS, Varambally S, Terris MK, Davies K, Ambs S, Bollag R, Apolo AB, Sreekumar A, Putluri N Abstract BACKGROUND: African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. METHODS: Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. RESULTS: Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. CONCLUSIONS: This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities. PMID: 30602056 [PubMed - as supplied by publisher]

Related Articles MetFlow: An interactive and integrated workflow for metabolomics data cleaning and differential metabolite discovery. Bioinformatics. 2019 Jan 02;: Authors: Shen X, Zhu ZJ Abstract Summary: Mass spectrometry-based metabolomics aims to profile the metabolic changes in biological systems and identify differential metabolites related to physiological phenotypes and aberrant activities. However, many confounding factors during data acquisition complicate metabolomics data, which is characterized by high dimensionality, uncertain degrees of missing and zero values, nonlinearity, unwanted variations, and non-normality. Therefore, prior to differential metabolite discovery analysis, various types of data cleaning such as batch alignment, missing value imputation, data normalization, and scaling are essentially required for data post-processing. Here, we developed an interactive web server, namely, MetFlow, to provide an integrated and comprehensive workflow for metabolomics data cleaning and differential metabolite discovery. Availability and implementation: The MetFlow is freely available on http://metflow.zhulab.cn/. Supplementary information: Supplementary data are available at Bioinformatics online. PMID: 30601938 [PubMed - as supplied by publisher]

Related Articles Obesity Leads to Distinct Metabolomic Signatures in the Follicular Fluid of Women Undergoing in vitro Fertilization. Am J Physiol Endocrinol Metab. 2019 Jan 02;: Authors: Ruebel ML, Piccolo BD, Mercer KE, Pack L, Moutos D, Shankar K, Andres A Abstract While obesity negatively influences the metabolic homeostasis of cells within a broad range of tissues, its impact on oocyte metabolism is not fully understood. Prior evidence suggests obesity increases expression of oocyte genes associated with inflammation, oxidative stress, and lipid metabolism; however, the metabolic impact of these genetic differences is not known. To address this gap, we conducted an exploratory assessment of the follicular fluid (FF) metabolome in 8 overweight/obese (OW) and 9 normal weight (NW) women undergoing in vitro fertilization. FF and serum were collected and analyzed by untargeted metabolomics using GC-QTOF-MS and CSH-ESI QTOF MS/MS. Untargeted metabolomics identified obesity-associated changes in FF metabolites related to oxidative stress/antioxidant capacity, xenometabolism/amino acid biosynthesis, and lipid metabolism. Discriminant FF metabolites included elevated uric acid, isothreonic acid, 1 unknown primary metabolite, and 6 unknown complex lipids in OW compared to NW women. Conversely, 2-dimethylacetal-ketoglucose, aminomalonate, 2 unknown primary metabolites, and 2 unknown complex lipids were decreased in FF of OW relative to NW women. Indole-3-propionic acid (IPA), a bacterial derived metabolite, was also decreased in both FF and serum of OW women (p<0.05). The significant correlation between antioxidant IPA in serum and FF (R= 0.95, p<0.0001), suggests a potential serum biomarker of FF antioxidant status or reflection of the gut metabolism interaction with the follicle. These results suggest that obesity has important consequences on the follicular environment during the pre-conception period, a window of time that may be important for lifestyle interventions to ameliorate obesity-associated risk factors. PMID: 30601701 [PubMed - as supplied by publisher]

Related Articles Metabolomics: A Powerful Tool to Enrich our Understanding of the Impact of Food on Health. Mol Nutr Food Res. 2019 Jan;63(1):e1870087 Authors: Brennan L PMID: 30601603 [PubMed - in process]

Related Articles High throughput screening of complex biological samples with mass spectrometry - from bulk measurements to single cell analysis. Analyst. 2019 Jan 02;: Authors: Kempa EE, Hollywood KA, Smith CA, Barran PE Abstract High throughput screening (HTS) of molecular analytes is in high demand from and implemented in many areas of chemistry, medicine and industrial biotechnology including the discovery of biomarkers and the development of new chemical entities. Despite its prevalence, technical challenges remain in many of the new application areas of HTS which require rapid results from complex mixtures, for example in: screening biotransformations; targeted metabolomics; and in locating drugs and/or metabolites in biological matrices. Common to all of these are lengthy and costly sample preparation stages, involving recovery from cell cultures, extractions followed by low throughput LC-MS/MS methods or specific fluorescence measurements. In the latter the target molecules need to be inherently fluorescent or to include a fluorescent label or tag which can adversely influence a cellular system. Direct infusion mass spectrometry coupled with robotic sample infusion is a viable contender for information rich HTS with sub-second analysis times, and recent developments in ambient ionisation have heralded a new era where screening can be performed on crude cell lysates or even from live cells. Besides commercially available technologies such as RapidFire, Acoustic Mist Ionisation, and the TriVersa ChipMate there are promising new developments from academic groups. Novel applications using desorption electrospray ionisation, microfluidics, rapid LC-separation and 'one cell' direct infusion methods offer much potential for increasing throughput from 'messy' complex samples and for significantly reducing the amount of material that needs to be analysed. Here we review recent advances in HTS coupled with MS with an emphasis on methods that reduce or remove all sample preparation and will facilitate single cell screening approaches. PMID: 30601490 [PubMed - as supplied by publisher]

Related Articles Structural characteristics and hepatoprotective potential of Aralia elata root bark polysaccharides and their effects on SCFAs produced by intestinal flora metabolism. Carbohydr Polym. 2019 Mar 01;207:256-265 Authors: Xia YG, Wang TL, Yu SM, Liang J, Kuang HX Abstract The structural characteristics of the polysaccharides from Aralia elata root barks (AERP) were systematically investigated by FT-IR, HPSEC-ELSD and colorimetric methods as well as by GCMS based monosaccharide compositions, Smith degradations, and methylation analysis. The result showed average molecular weights of AERP were between 42.7 kDa and 93.9 kDa. AERP was composed of Ara, Rha, GlcA, Man, Glc, and Gal in a molar ratio of 22.2: 10.3: 8.1: 32.7: 5.7: 21.2 along with a small number of sulfate (3.38%) and acetyl (4.87%) groups. The abundant glycosidic linkages of Man, Ara, Gal, and Rha were observed as more than 90% of all the monosaccharides detected. Studies to evaluate hepatoprotective potentials of AERP showed that they had potent hepatoprotective effects in vivo in carbon tetrachloride-induced acute liver injury (CIALI) in mice by histopathological evaluation, biochemical examinations and ELISA assays. GCMS was further used to determine the effects of AERP on the chemical profiles of nine common short-chain fatty acids (SCFAs) produced by intestinal flora metabolism in CIALI mice. These findings not only provide novel insights into the pharmacological actions of AERP on the protection from CIALI in mice, but they also demonstrate that determining SCFA profiles by targeted GC-MS metabolomics is an effective technique to investigate the molecular mechanisms of the effects of plant polysaccharides on intestinal flora metabolism. PMID: 30600007 [PubMed - in process]

Related Articles Impact of conventional/non-conventional extraction methods on the untargeted phenolic profile of Moringa oleifera leaves. Food Res Int. 2019 Jan;115:319-327 Authors: Rocchetti G, Blasi F, Montesano D, Ghisoni S, Marcotullio MC, Sabatini S, Cossignani L, Lucini L Abstract The impact of different extraction methods, namely maceration, homogenizer-assisted extraction, rapid solid-liquid dynamic extraction, microwave-assisted extraction and ultrasound-assisted extraction, on polyphenols of Moringa oleifera leaves was studied. The phenolic composition of alcoholic (methanol 100%) and hydroalcoholic (methanol/water 50:50, v/v) extracts was compared by using an untargeted metabolomics-based profiling approach followed by multivariate statistics. With this aim, ultra-high-pressure liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometry was used to profile phenolic compounds under the different extraction conditions. Besides, the in vitro antioxidant activities of Moringa leaves were also investigated as ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). The metabolomic approach allowed to putatively annotate 262 phenolic compounds. In particular, glycosidic forms of quercetin (i.e., quercetin 3-O-galactoside, quercetin 3-O-glucoside, and quercetin 4'-O-glucoside) were the most represented compounds among flavonoids. Furthermore, protocatechuic acid was found to be the most abundant hydroxybenzaldheyde derivative, while the isomeric forms of hydroxybenzoic acid characterized the phenolic acids class. Overall, the extractions in methanol 100% were found to be the most effective for phenolic compounds recovering, when compared with those in methanol/water (50:50, v/v). Homogenizer-assisted extraction of M. oleifera leaves using 100% methanol allowed extracting the highest amounts of polyphenols (35.19 mg/g) and produced the highest oxygen radical absorbance capacity (536.27 μmol Trolox Equivalents/g). The supervised orthogonal projection to latent structures discriminant analysis identified phenolic acids as the phenolic class mostly affected by the different extraction technologies. These findings demonstrate that each extraction method promoted the recovery of specific phenolic subclasses with different efficiencies. PMID: 30599948 [PubMed - in process]

Related Articles Killing method affects the browning and the quality of the protein fraction of Black Soldier Fly (Hermetia illucens) prepupae: a metabolomics and proteomic insight. Food Res Int. 2019 Jan;115:116-125 Authors: Leni G, Caligiani A, Sforza S Abstract Insects are being explored as novel protein sources in order to overcome the future food demands connected to world growing population. Insects for food/feed uses are currently slowly killed through freezing by most insect rearing companies, and typically, enzymatic browning takes place in the insect proteins fractions. However, very little is known about the influence of these enzymatic reactions on the protein physical, chemical, nutritional and technological properties. In this work a metabolomics and proteomic study was conducted on Black Soldier Fly (Hermetia illucens) prepupae, killed by two different methods: freezing (commonly used), and blanching (with the aim to inhibit the enzymatic activities). Proton nuclear magnetic resonance (1H NMR) metabolomics demonstrated that slow killing method by freezing, compared with blanching, elicits the activation of several enzymatic pathways, among them melanisation with tyrosine consumption, energetic metabolism and lipolysis. These metabolic changes have an impact also on protein nutritional quality, with a loss of cysteine and lysine, likely involved in the process of melanisation and enzymatic browning. A strong effect was also observed on protein extractability: proteins from prepupae killed by blanching were found to be more extractable in milder conditions by chemical methods, and more prone to enzymatic digestion (97% of proteins released in solution upon proteolysis) than proteins from prepupae killed by freezing. All these data indicate that killing by blanching inhibits the browning reaction and other enzymatic changes occurring during slow killing by freezing, increasing the extractability of proteins in aqueous solutions, avoiding essential amino acid loss, and improving enzymatic digestibility. PMID: 30599922 [PubMed - in process]

Related Articles Metabolite changes in blood predict the onset of tuberculosis. Nat Commun. 2018 12 06;9(1):5208 Authors: Weiner J, Maertzdorf J, Sutherland JS, Duffy FJ, Thompson E, Suliman S, McEwen G, Thiel B, Parida SK, Zyla J, Hanekom WA, Mohney RP, Boom WH, Mayanja-Kizza H, Howe R, Dockrell HM, Ottenhoff THM, Scriba TJ, Zak DE, Walzl G, Kaufmann SHE, GC6-74 consortium Abstract New biomarkers of tuberculosis (TB) risk and disease are critical for the urgently needed control of the ongoing TB pandemic. In a prospective multisite study across Subsaharan Africa, we analyzed metabolic profiles in serum and plasma from HIV-negative, TB-exposed individuals who either progressed to TB 3-24 months post-exposure (progressors) or remained healthy (controls). We generated a trans-African metabolic biosignature for TB, which identifies future progressors both on blinded test samples and in external data sets and shows a performance of 69% sensitivity at 75% specificity in samples within 5 months of diagnosis. These prognostic metabolic signatures are consistent with development of subclinical disease prior to manifestation of active TB. Metabolic changes associated with pre-symptomatic disease are observed as early as 12 months prior to TB diagnosis, thus enabling timely interventions to prevent disease progression and transmission. PMID: 30523338 [PubMed - indexed for MEDLINE]

Related Articles On Mass Ambiguities in High-Resolution Shotgun Lipidomics. Anal Chem. 2017 03 07;89(5):2986-2994 Authors: Bielow C, Mastrobuoni G, Orioli M, Kempa S Abstract Mass-spectrometry-based lipidomics aims to identify as many lipid species as possible from complex biological samples. Due to the large combinatorial search space, unambiguous identification of lipid species is far from trivial. Mass ambiguities are common in direct-injection shotgun experiments, where an orthogonal separation (e.g., liquid chromatography) is missing. Using the rich information within available lipid databases, we generated a comprehensive rule set describing mass ambiguities, while taking into consideration the resolving power (and its decay) of different mass analyzers. Importantly, common adduct species and isotopic peaks are accounted for and are shown to play a major role, both for perfect mass overlaps due to identical sum formulas and resolvable mass overlaps. We identified known and hitherto unknown mass ambiguities in high- and ultrahigh resolution data, while also ranking lipid classes by their propensity to cause ambiguities. On the basis of this new set of ambiguity rules, guidelines and recommendations for experimentalists and software developers of what constitutes a solid lipid identification in both MS and MS/MS were suggested. For researchers new to the field, our results are a compact source of ambiguities which should be accounted for. These new findings also have implications for the selection of internal standards, peaks used for internal mass calibration, optimal choice of instrument resolution, and sample preparation, for example, in regard to adduct ion formation. PMID: 28193003 [PubMed - indexed for MEDLINE]

Related Articles Novel metabolic disturbances in marginal vitamin B6-deficient rat heart. J Nutr Biochem. 2018 Dec 04;65:26-34 Authors: Kumrungsee T, Nirmagustina DE, Arima T, Onishi K, Sato K, Kato N, Yanaka N Abstract Vitamin B6 deficiency is associated with cardiovascular disease (CVD). Although plasma biomarkers have been proposed, no studies have yet directly profiled heart tissue, and the mechanisms have to be fully defined. Thus, in order to provide better insight into vitamin B6-deficient effects on cardiac functions, we sought to identify the metabolic profile in heart tissue consequent to change in dietary vitamin B6 levels by applying metabolomics. Heart tissues of rats fed a basal diet containing a marginal vitamin B6-deficient, vitamin B6-recommended or vitamin B6-supplemented level were analyzed by metabolomics analysis. Among over 500 detected metabolites, imidazole metabolites including carnosine, anserine, homocarnosine and histamine exhibited the highest decrease upon vitamin B6 deficiency (>-45%, P<.01), along with their precursors β-alanine, γ-aminobutyric acid (GABA) and 1-methylhistidine. Ornithine was the only metabolite exhibiting an increased level in the vitamin B6-deficient group. Vitamin B6 deficiency significantly attenuated the activity of heart tissue glutamate decarboxylase (GAD), although there was undetectable activity of aspartate decarboxylase (ADC), suggesting that the involvement of vitamin B6 in imidazole metabolite synthesis occurs partly through GABA production by regulating GAD rather than through a straightforward β-alanine production pathway via ADC in the heart. Notably, vitamin B6 deficiency significantly attenuated citric acid cycle metabolite levels, suggesting cardiac energy metabolism impairment. This study provides a new link between vitamin B6 and cardiac functions, in which marginal vitamin B6 deficiency impairs imidazole and energy metabolism in heart. This newly revealed cardiac metabolic profile may reveal novel molecular targets or foodstuffs for CVD prevention. PMID: 30599394 [PubMed - as supplied by publisher]

Related Articles Predictive metabolic signatures for the occurrence and development of diabetic nephropathy and the intervention of Ginkgo biloba leaves extract based on gas or liquid chromatography with mass spectrometry. J Pharm Biomed Anal. 2018 Dec 26;166:30-39 Authors: Du Y, Xu BJ, Deng X, Wu XW, Li YJ, Wang SR, Wang YN, Ji S, Guo MZ, Yang DZ, Tang DQ Abstract Diabetic nephropathy (DN) is one of the leading causes of death in diabetes mellitus (DM). Early warning and therapy has significant clinical value for DN. This research sought to find biomarkers to predict the occurrence and development of DN and the intervention of Ginkgo biloba leaves extract (GBE) by quantifying fatty acids, amino acids, and nucleosides and nucleobases in rat plasma. Samples were respectively collected at the weekend of 5-10 weeks after diabetic rats induced by streptozotocin were defined. Plasma fasting blood-glucose, kidney index, blood urea nitrogen, creatinine, urine albumin excretion and ultrastructural morphology of kidney were measured or observed. Fatty acids, amino acids and nucleosides and nucleobases in rat plasma were analyzed by gas chromatography or liquid phase chromatography and mass spectrometry, respectively. From the biochemical index and morphological change of kidney, the rats from the 5th to 7th week were in the stage of DM while from the begin of 8th week the rats were suggested in the early stage of DN. The results of quantitative metabolomics showed that 16 differential metabolites were related to the progression of DN, and oleic acid, glutamate and guanosine might be the potential biomarkers of kidney injury. 14 differential metabolites were related to GBE against the progression of DN, while oleic acid and glutamate might be the potential biomarkers of GBE against kidney injury. Those findings potentially promote the understanding of the pathogenic progression of DN and reveal the therapeutic mechanism of GBE against DN. PMID: 30599279 [PubMed - as supplied by publisher]

Related Articles A Lipidomics Study Reveals Lipid Signatures Associated with Early Allograft Dysfunction in Living Donor Liver Transplantation. J Clin Med. 2018 Dec 29;8(1): Authors: Tsai HI, Lo CJ, Zheng CW, Lee CW, Lee WC, Lin JR, Shiao MS, Cheng ML, Yu HP Abstract Liver transplantation has become the ultimate treatment for patients with end stage liver disease. However, early allograft dysfunction (EAD) has been associated with allograft loss or mortality after transplantation. We aim to utilize a metabolomic platform to identify novel biomarkers for more accurate correlation with EAD using blood samples collected from 51 recipients undergoing living donor liver transplantation (LDLT) by 1H-nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography coupled with mass spectrometry (LC-MS). Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were used to search for a relationship between the metabolomic profiles and the presence of EAD.Cholesteryl esters (CEs), triacylglycerols (TGs), phosphatidylcholines (PCs) and lysophosphatidylcholine (lysoPC) were identified in association with EAD and a combination of cholesterol oleate, PC (16:0/16:0), and lysoPC (16:0) gave an optimal area under the curve (AUC) of 0.9487 and 0.7884 in the prediction of EAD and in-hospital mortality, respectively after LDLT. Such biomarkers may add as a potential clinical panel for the prediction of graft function and mortality after LDLT. PMID: 30597989 [PubMed]

Related Articles Metabolic fingerprint of insulin resistance in human polymorphonuclear leucocytes. PLoS One. 2018;13(7):e0199351 Authors: Palomino-Schätzlein M, Simó R, Hernández C, Ciudin A, Mateos-Gregorio P, Hernández-Mijares A, Pineda-Lucena A, Herance JR Abstract The present study was aimed at determining the metabolic profile of PMNs in obese subjects, and to explore its potential relationship with insulin resistance (IR). To achieve this goal, a pilot clinical study was performed using PMNs from 17 patients with obesity and IR, and 17 lean controls without IR, which was validated in an additional smaller cohort (consisting of 10 patients and 10 controls). PMNs were isolated from peripheral blood and nuclear magnetic resonance was used to perform the metabolomic analysis. A total of 48 metabolites were quantified. The main metabolic change found in PMNs was a significant increase in 2-aminoisobutyric acid with a direct correlation with HOMA-IR (p<0.001), BMI (p<0.000001) and waist circumference (p<0.000001). By contrast, a decrease of 3-hydroxyisovalerate was observed with an inverse correlation with HOMA-IR (p = 0.001), BMI (p = 0.001) and waist circumference (p = 0.0001). Notably, the metabolic profile in plasma was different than that obtained in PMNs. In summary, our results suggest that the change in 3-hydroxyisovalerate and 2-aminoisobutyric is the key metabolic fingerprint in PMNs of obese subjects with IR. In addition, our methodology could be an easy and reliable tool for monitoring the effect of treatments in the setting of precision medicine. PMID: 30005063 [PubMed - indexed for MEDLINE]

Related Articles Time-Dependent Lactate Production and Amino Acid Utilization in Cultured Astrocytes Under High Glucose Exposure. Mol Neurobiol. 2018 02;55(2):1112-1122 Authors: Wang D, Zhao L, Zheng H, Dong M, Pan L, Zhang X, Zhang H, Gao H Abstract Accumulating investigations have focused on the severity of central nervous system (CNS) complications in diabetic patients. The effects of the high glucose (HG) probably attribute to the metabolic disturbances in CNS. Astrocytes, with powerful ability of metabolic regulation, play crucial roles in physiological and pathological processes in CNS. Hence, an in-depth analysis as to metabolic alterations of astrocytes exposure to HG would facilitate to explore the underlying pathogenesis. In this study, the 1H NMR-based metabonomic approach was performed to characterize the metabolic variations of intracellular metabolites and corresponding culture media in a time-dependent manner. Our results revealed a significant elevation in lactate production and release. Four amino acids, leucine, isoleucine, methionine and tyrosine, were the most important metabolites for utilization. Also, profound disturbances of several metabolic pathways, including osmoregulation, energy metabolism, and cellular biosynthesis were observed. In that sense, the detailed information of astrocyte metabolism under HG exposure provides us a comprehensive understanding of the intrinsic metabolic disorders in CNS during hyperglycemia or diabetes. PMID: 28092089 [PubMed - indexed for MEDLINE]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/01/01PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/01/01PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.