PubMed

Related Articles Improved Algal Toxicity Test System for Robust Omics-Driven Mode-of-Action Discovery in Chlamydomonas reinhardtii. Metabolites. 2019 May 10;9(5): Authors: Schade S, Butler E, Gutsell S, Hodges G, Colbourne JK, Viant MR Abstract Algae are key components of aquatic food chains. Consequently, they are internationally recognised test species for the environmental safety assessment of chemicals. However, existing algal toxicity test guidelines are not yet optimized to discover molecular modes of action, which require highly-replicated and carefully controlled experiments. Here, we set out to develop a robust, miniaturised and scalable Chlamydomonas reinhardtii toxicity testing approach tailored to meet these demands. We primarily investigated the benefits of synchronised cultures for molecular studies, and of exposure designs that restrict chemical volatilisation yet yield sufficient algal biomass for omics analyses. Flow cytometry and direct-infusion mass spectrometry metabolomics revealed significant and time-resolved changes in sample composition of synchronised cultures. Synchronised cultures in sealed glass vials achieved adequate growth rates at previously unachievably-high inoculation cell densities, with minimal pH drift and negligible chemical loss over 24-h exposures. Algal exposures to a volatile test compound (chlorobenzene) yielded relatively high reproducibility of metabolic phenotypes over experimental repeats. This experimental test system extends existing toxicity testing formats to allow highly-replicated, omics-driven, mode-of-action discovery. PMID: 31083411 [PubMed]

Related Articles T-Probe: An Integrated Microscale Device for Online In Situ Single Cell Analysis and Metabolic Profiling Using Mass Spectrometry. Anal Chem. 2018 09 18;90(18):11078-11085 Authors: Liu R, Pan N, Zhu Y, Yang Z Abstract The exploration of single cells reveals cell heterogeneity and biological principle of cellular metabolism. Although a number of mass spectrometry (MS) based single cell MS (SCMS) techniques have been dedicatedly developed with high efficiency and sensitivity, limitations still exist. In this work, we introduced a microscale multifunctional device, the T-probe, which integrates cellular contents extraction and immediate ionization, to implement online in situ SCMS analysis at ambient conditions with minimal sample preparation. With high sensitivity and reproducibility, the T-probe was employed for MS analysis of single HeLa cells under control and anticancer drug treatment conditions. Intracellular species and xenobiotic metabolites were detected, and changes of cellular metabolic profiles induced by drug treatment were measured. Combining SCMS experiments with statistical data analyses, including Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) and two-sample t-test, we provided biological insights into cellular metabolic response to drug treatment. Online MS/MS analysis was conducted at single cell level to identify species of interest, including endogenous metabolites and the drug compound. Using the T-probe SCMS technique combined with comprehensive data analyses, we provide an approach to understanding cellular metabolism and evaluate chemotherapies at the single cell level. PMID: 30119596 [PubMed - indexed for MEDLINE]

17 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 2019/05/14PubMed 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.

17 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 2019/05/14PubMed 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.

Related Articles Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus. J Assist Reprod Genet. 2019 May 12;: Authors: Tardieu A, Chazelas P, Faye PA, Favreau F, Nadal-Desbarats L, Sallée C, Margueritte F, Couquet CY, Marquet P, Guellec CB, Gauthier T Abstract INTRODUCTION: The development of uterine transplantation (UTx) from deceased donors requires knowledge of the tolerance of the uterus to prolonged cold ischemia (CI). This can be evaluated through the use of biological parameters to assess degradation of the organ between its procurement and transplantation. The objective of this study was to analyze changes in the metabolic composition of the storage solution in cases of prolonged CI in uteri from ewes. METHODS: Eighteen uterine auto-transplantations were performed in ewes. CI time was 1 h (T1) or 24 h (T24). Samples of Celsior® were taken when the explanted uterus was flushed (T0) and at the end of CI. A dual approach to metabolic analyses was followed: targeted biochemical analyses targeting several predefined metabolites and non-targeted metabolomics analyses based on nuclear magnetic resonance (NMR). RESULTS: Metabolic analyses were performed on 16 explanted uteri. Metabolomic profiles differed significantly between T1 and T24 (p = 0.003). Hypoxia-associated degradation of the organ was demonstrated by the significantly higher lactate levels at T24 than at T1 (p < 0.05), accompanied by cell lysis, and significantly higher levels of creatine kinase activity in T24 than in T1 uteri (p < 0.05). Oxidative stress increased over time, with a significantly higher oxidized glutathione/glutathione ratio for T24 than for T1 uteri (p < 0.05). CONCLUSION: The metabolic results indicate a significant degradation of the uterus during 24 h of CI. Metabolic analysis of the storage solution could be used as a non-invasive tool for evaluating uterine degradation during CI before transplantation. PMID: 31079269 [PubMed - as supplied by publisher]

Related Articles Dydrogesterone exposure induces zebrafish ovulation but leads to oocytes over-ripening: An integrated histological and metabolomics study. Environ Int. 2019 May 09;128:390-398 Authors: Jiang YX, Shi WJ, Ma DD, Zhang JN, Ying GG, Zhang H, Ong CN Abstract Dydrogesterone (DDG) is a synthetic progestin widely used in numerous gynecological diseases. DDG has been shown to disturb fish reproduction, however, the mechanism is still unclear. Here we studied the histological changes and differences of metabolome between exposed and control fish gonads after exposure of zebrafish (Danio rerio) embryos to 2.8, 27.6, and 289.8 ng/L DDG until sexual maturity for a total of 140 days. Dydrogesterone exposure led to male-biased zebrafish sex ratios. Histological examination revealed that DDG induced postovulatory follicles and atretic follicles in the ovary of the female fish. Postovulatory follicles indicated the occurrence of ovulation. DDG also increased spermatids and spermatozoa in the male fish testis, suggesting promotion of spermatogenesis. Ovarian metabolome showed that DDG increased the concentrations of free amino acids, urea, putrescine, free fatty acids, acylcarnitines, lysophospholipids, and other metabolites catabolized from phospholipids. Most of these metabolites are biodegradation products of proteins and lipids, suggesting the existence of ovulated oocytes over-ripening. Further, DDG upregulated arachidonic acid (AA) and its 5‑lipoxygenase (5-LOX) metabolites 5‑oxo‑6,8,11,14‑eicosatetraenoic acid (5-oxo-ETE) in the ovary, which could lead to suppression of AA cyclooxygenase (COX) metabolite prostaglandin F2α (PGF2α). It is believed that AA induced oocyte maturation, while 5-oxo-ETE and related metabolites in purinergic signaling promoted ovulation. Whereas, the suppression of PGF2α production might block spawning and damaged follicular tissue digestion, which explained the oocytes over-ripening and atretic follicles in the treated ovary. Overall, our results suggested that DDG exposure induced zebrafish oocyte maturation and ovulation but led to oocytes over-ripening via the AA metabolic pathway and purinergic signaling. PMID: 31078873 [PubMed - as supplied by publisher]

Related Articles 2H and 13C metabolic flux analysis elucidates in vivo thermodynamics of the ED pathway in Zymomonas mobilis. Metab Eng. 2019 May 09;: Authors: Jacobson TB, Adamczyk PA, Stevenson DM, Regner M, Ralph J, Reed J, Amador-Noguez D Abstract Zymomonas mobilis is an industrially relevant bacterium notable for its ability to rapidly ferment simple sugars to ethanol using the Entner-Doudoroff (ED) glycolytic pathway, an alternative to the well-known Embden-Meyerhof-Parnas (EMP) pathway used by most organisms. Recent computational studies have predicted that the ED pathway is substantially more thermodynamically favorable than the EMP pathway, a potential factor explaining the high glycolytic rate in Z. mobilis. Here, to investigate the in vivo thermodynamics of the ED pathway and central carbon metabolism in Z. mobilis, we implemented a network-level approach that integrates quantitative metabolomics with 2H and 13C metabolic flux analysis to estimate reversibility and Gibbs free energy (ΔG) of metabolic reactions. This analysis revealed a strongly thermodynamically favorable ED pathway in Z. mobilis that is nearly twice as favorable as the EMP pathway in E. coli or S. cerevisiae. The in vivo step-by-step thermodynamic profile of the ED pathway was highly similar to previous in silico predictions, indicating that maximizing ΔG for each pathway step likely constitutes a cellular objective in Z. mobilis. Our analysis also revealed novel features of Z. mobilis metabolism, including phosphofructokinase-like enzyme activity, tricarboxylic acid cycle anaplerosis via PEP carboxylase, and a metabolic imbalance in the pentose phosphate pathway resulting in excretion of shikimate pathway intermediates. The integrated approach we present here for in vivo ΔG quantitation may be applied to the thermodynamic profiling of pathways and metabolic networks in other microorganisms and will contribute to the development of quantitative models of metabolism. PMID: 31078792 [PubMed - as supplied by publisher]

Related Articles Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort. Alzheimers Dement. 2019 Apr 28;: Authors: Kim M, Snowden S, Suvitaival T, Ali A, Merkler DJ, Ahmad T, Westwood S, Baird A, Proitsi P, Nevado-Holgado A, Hye A, Bos I, Vos S, Vandenberghe R, Teunissen C, Ten Kate M, Scheltens P, Gabel S, Meersmans K, Blin O, Richardson J, De Roeck E, Sleegers K, Bordet R, Rami L, Kettunen P, Tsolaki M, Verhey F, Sala I, Lléo A, Peyratout G, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Engelborghs S, Frisoni GB, Molinuevo JL, Wallin A, Popp J, Martinez-Lage P, Bertram L, Barkhof F, Ashton N, Blennow K, Zetterberg H, Streffer J, Visser PJ, Lovestone S, Legido-Quigley C Abstract INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. RESULTS: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. DISCUSSION: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures. PMID: 31078433 [PubMed - as supplied by publisher]

Related Articles Evaluating sub-lethal stress from Roundup® exposure in Artemia franciscana using 1H NMR and GC-MS. Aquat Toxicol. 2019 May 01;212:77-87 Authors: Morgan MA, Griffith CM, Dinges MM, Lyon YA, Julian RR, Larive CK Abstract Global salinization trends present an urgent need for methods to monitor aquatic ecosystem health and characterize known and emerging stressors for water bodies that are becoming increasingly saline. Environmental metabolomics methods that combine quantitative measurements of metabolite levels and multivariate statistical analysis are powerful tools for ascertaining biological impacts and identifying potential biomarkers of exposure. We propose the use of the saltwater aquatic crustacean, Artemia franciscana, as a model organism for environmental metabolomics in saltwater ecosystems. Artemia are a good choice for ecotoxicity assays and metabolomics analysis because they have a short life cycle, their hemolymph is rich in metabolites and they tolerate a wide salinity range. In this work we explore the potential of Artemia franciscana for environmental metabolomics through exposure to the broad-spectrum herbicide, glyphosate. The LC50 for a 48 h exposure of Roundup® was determined to be 237 ± 23 ppm glyphosate in the Roundup® formulation. Artemia cysts were hatched and exposed to sub-lethal glyphosate concentrations of 1.00, 10.0, 50.0, or 100 ppm glyphosate in Roundup®. We profiled 48 h old Artemia extracts using 1H NMR and GC-MS. Dose-dependent metabolic perturbation was evident for several metabolites using univariate and multivariate analyses. Metabolites significantly affected by Roundup® exposure included aspartate, formate, betaine, glucose, tyrosine, phenylalanine, gadusol, and isopropylamine. Biochemical pathway analysis with the KEGG database suggests impairment of carbohydrate and energy metabolism, folate-mediated one-carbon metabolism, Artemia molting and development, and microbial metabolism. PMID: 31077969 [PubMed - as supplied by publisher]

Related Articles Experiments with direct detection of multiple FIDs. J Magn Reson. 2019 Apr 30;304:16-34 Authors: Kupče Ē, Mote KR, Madhu PK Abstract Pulse schemes with direct observation of multiple free induction decays (FIDs) offer a dramatic increase in the spectral information content of NMR experiments and often yield substantial improvement in measurement sensitivity per unit time. Availability of multiple receivers on the state-of-the-art commercial spectrometers allows spectra from different nuclear species to be recorded in parallel routinely. Experiments with multi-FID detection have been designed with both, homonuclear and multinuclear acquisition. We provide a brief overview of such techniques designed for applications in liquid- and solid- state NMR as well as in hyperpolarized samples. Here we show how these techniques have led to design of experiments that allow structure elucidation of small molecules and resonance assignment in proteins from a single measurement. Probes with multiple RF micro-coils routed to multiple NMR receivers provide an alternative way of increasing the throughput of modern NMR systems. Solid-state NMR experiments have also benefited immensely from both parallel and simultaneous FID acquisition in a variety of multi-dimensional pulse schemes. We believe that multi-FID detection will become an essential component of the future NMR methodologies effectively increasing the information content of NMR experiments and reducing the cost of NMR analysis. PMID: 31077929 [PubMed - as supplied by publisher]

Related Articles Saliva NMR metabolomics: analytical issues in paediatric oral health research. Oral Dis. 2019 May 11;: Authors: Pereira JL, Duarte D, Carneiro TJ, Ferreira S, Cunha B, Soares D, Costa AL, Gil AM Abstract OBJECTIVES: Saliva metabolome is a promising diagnostic tool concerning oral and systemic diseases. We aimed at establishing a suitable protocol for saliva collection and gauging the relative impacts of gender, dentition stage and caries on the saliva metabolome of a small children cohort. SUBJECTS AND METHODS: A Nuclear Magnetic Resonance-based metabolomics cross-sectional study of children saliva (n=38) compared the effects of i) stimulation and unstimulation conditions and ii) collection through passive drool and using an absorbing device. Multivariate and univariate statistical analysis were applied to evaluate such effects, and those related to gender, dentition stage and caries. RESULTS: No significant differences were found between unstimulated and stimulated saliva and the former was used for subsequent studies. Swab collection induced significant changes in sample composition, indicating passive drool as preferential. The impacts of gender and dentition stage were not significant compared to that of caries, which induced variations in the levels of 21 metabolites. These comprised amino acids and monosaccharides observed for the first time to our knowledge regarding children caries, suggesting protein hydrolysis and deglycosylation. CONCLUSIONS: Unstimulated passive drool saliva metabolome may carry a caries signature. This article is protected by copyright. All rights reserved. PMID: 31077633 [PubMed - as supplied by publisher]

Related Articles Effects of Thiosulfate as a Sulfur Source on Plant Growth, Metabolites Accumulation and Gene Expression in Arabidopsis and Rice. Plant Cell Physiol. 2019 May 11;: Authors: Nakajima T, Kawano Y, Ohtsu I, Maruyuama-Nakashita A, Allahham A, Sato M, Sawada Y, Hirai MY, Yokoyama T, Ohkama-Ohtsu N Abstract Plants are considered to absorb sulfur from their roots in the form of sulfate. In bacteria like Escherichia coli, thiosulfate is a preferred sulfur source. It is converted into cysteine (Cys). This transformation consumes less NADPH and ATP than sulfate assimilation into Cys. In Saccharomyces cerevisiae, thiosulfate promoted growth more than sulfate. In the present study, the availability of thiosulfate, the metabolite transformations, and gene expressions it induces were investigated in Arabidopsis and rice as model dicots and monocots, respectively. In Arabidopsis the thiosulfate-amended plants had lower biomass than those receiving sulfate when sulfur concentrations in the hydroponic medium were above 300 μM. In contrast, rice biomass was similar for plants raised on thiosulfate and sulfate at 300 μM sulfur. Therefore, both plants can use thiosulfate but it is a better sulfur source for rice. In both plants, thiosulfate levels significantly increased in roots following thiosulfate application, indicating that the plants absorbed thiosulfate into their root cells. Thiosulfate is metabolized in plants by a different pathway from that used for sulfate metabolism. Thiosulfate increases plant sulfide and cysteine-persulfide levels which means that plants are in a more reduced state with thiosulfate than with sulfate. The microarray analysis of Arabidopsis roots revealed that 13 genes encoding Cys-rich proteins were upregulated more with thiosulfate than with sulfate. These results together with those of the widely-targeted metabolomics analysis were used to proposes a thiosulfate assimilation pathway in plants. PMID: 31077319 [PubMed - as supplied by publisher]

Related Articles Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State. Inflamm Bowel Dis. 2019 May 11;: Authors: Diab J, Hansen T, Goll R, Stenlund H, Ahnlund M, Jensen E, Moritz T, Florholmen J, Forsdahl G Abstract BACKGROUND: The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects. METHODS: Treatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified. RESULTS: The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups. CONCLUSION: This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state. PMID: 31077307 [PubMed - as supplied by publisher]

Related Articles Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease. Dig Dis Sci. 2019 May 10;: Authors: Gao B, Lang S, Duan Y, Wang Y, Shawcross DL, Louvet A, Mathurin P, Ho SB, Stärkel P, Schnabl B Abstract BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis. PMID: 31076986 [PubMed - as supplied by publisher]

Related Articles Differential Transcriptomic and Metabolomic Responses in the Liver of Nile Tilapia (Oreochromis niloticus) Exposed to Acute Ammonia. Mar Biotechnol (NY). 2019 May 10;: Authors: Zhu ZX, Jiang DL, Li BJ, Qin H, Meng ZN, Lin HR, Xia JH Abstract Ammonia is toxic to aquatic animal. Currently, only limited works were reported on the responses of aquatic animals after ammonia exposure using "omics" technologies. Tilapia suffers from the stress of ammonia-nitrogen during intensive recirculating aquaculture. Optimizing ammonia stress tolerance has become an important issue in tilapia breeding. The molecular and biochemical mechanisms of ammonia-nitrogen toxicity have not been understood comprehensively in tilapia yet. In this study, using RNA-seq and gas chromatograph system coupled with a Pegasus HT time-of-flight mass spectrometer (GC-TOF-MS) techniques, we investigated differential expressed genes (DEGs) and metabolomes in the liver at 6 h post-challenges (6 hpc) and 24 h post-challenges (24 hpc) under high concentration of ammonia-nitrogen treatment. We detected 2258 DEGs at 6 hpc and 315 DEGs at 24 hpc. Functional enrichment analysis indicated that DEGs were significantly associated with cholesterol biosynthesis, steroid and lipid metabolism, energy conservation, and mitochondrial tissue organization. Metabolomic analysis detected 31 and 36 metabolites showing significant responses to ammonia-nitrogen stress at 6 and 24 hpc, respectively. D-(Glycerol 1-phosphate), fumaric acid, and L-malic acid were found significantly down-regulated at both 6 and 24 hpc. The integrative analysis of transcriptomics and metabolomics suggested considerable alterations and precise control of gene expression at both physiological and molecular levels in response to the stress of ammonia-nitrogen in tilapia. PMID: 31076921 [PubMed - as supplied by publisher]

Related Articles Characterization of Glycolytic Enzymes and Pyruvate Kinase M2 in Type 1 and 2 Diabetic Nephropathy. Diabetes Care. 2019 May 10;: Authors: Gordin D, Shah H, Shinjo T, St-Louis R, Qi W, Park K, Paniagua SM, Pober DM, Wu IH, Bahnam V, Brissett MJ, Tinsley LJ, Dreyfuss JM, Pan H, Dong Y, Niewczas MA, Amenta P, Sadowski T, Kannt A, Keenan HA, King GL Abstract OBJECTIVE: Elevated glycolytic enzymes in renal glomeruli correlated with preservation of renal function in the Medalist Study, individuals with ≥50 years of type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings in a separate cohort of type 1 and type 2 diabetes and discover new circulatory biomarkers for renal protection through proteomics and metabolomics of Medalists' plasma. We hypothesize that increased glycolytic flux and improved mitochondrial biogenesis will halt the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: Immunoblots analyzed selected glycolytic and mitochondrial enzymes in postmortem glomeruli of non-Medalists with type 1 diabetes (n = 15), type 2 diabetes (n = 19), and no diabetes (n = 5). Plasma proteomic (SOMAscan) (n = 180) and metabolomic screens (n = 214) of Medalists with and without stage 3b chronic kidney disease (CKD) were conducted and significant markers validated by ELISA. RESULTS: Glycolytic (PKM1, PKM2, and ENO1) and mitochondrial (MTCO2) enzymes were significantly elevated in glomeruli of CKD- versus CKD+ individuals with type 2 diabetes. Medalists' plasma PKM2 correlated with estimated glomerular filtration rate (r 2 = 0.077; P = 0.0002). Several glucose and mitochondrial enzymes in circulation were upregulated with corresponding downregulation of toxic metabolites in CKD-protected Medalists. Amyloid precursor protein (APP) was also significantly upregulated, tumor necrosis factor receptors downregulated, and both confirmed by ELISA. CONCLUSIONS: Elevation of enzymes involved in the metabolism of intracellular free glucose and its metabolites in renal glomeruli are connected to preserving kidney function in both type 1 and type 2 diabetes. The renal profile of elevated glycolytic enzymes and reduced toxic glucose metabolites is reflected in the circulation, supporting their use as biomarkers for endogenous renal protective factors in people with diabetes. PMID: 31076418 [PubMed - as supplied by publisher]

Related Articles A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia. Chin J Nat Med. 2019 Apr;17(4):275-290 Authors: Hua YL, Ma Q, Yuan ZW, Zhang XS, Yao WL, Ji P, Hu JJ, Wei YM Abstract Danggui Buxue Tang (DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague-Dawley(SD) rats were randomly divided into 3 groups including control (NC, Saline), the DBT (at a dose of 8.10 g-1), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry (LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component-target protein interaction network and establish a component, protein and hub metabolite protein-protein interaction (PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-l-methionine, glycine, l-cysteine, arachidonic acid (AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia. PMID: 31076131 [PubMed - in process]

Related Articles NMR-Based Tissular and Developmental Metabolomics of Tomato Fruit. Metabolites. 2019 May 09;9(5): Authors: Lemaire-Chamley M, Mounet F, Deborde C, Maucourt M, Jacob D, Moing A Abstract Fruit is a complex organ containing seeds and several interconnected tissues with dedicated roles. However, most biochemical or molecular studies about fleshy fruit development concern the entire fruit, the fruit without seeds, or pericarp only. We studied tomato (Solanum lycopersicum) fruit at four stages of development (12, 20, 35, and 45 days post-anthesis). We separated the seeds and the other tissues, exocarp, mesocarp, columella with placenta and locular tissue, and analyzed them individually using proton NMR metabolomic profiling for the quantification of major polar metabolites, enzymatic analysis of starch, and LC-DAD analysis of isoprenoids. Pericarp tissue represented about half of the entire fruit mass only. The composition of each fruit tissue changed during fruit development. An ANOVA-PCA highlighted common, and specific metabolite trends between tissues e.g., higher contents of chlorogenate in locular tissue and of starch in columella. Euclidian distances based on compositional data showed proximities within and between tissues. Several metabolic regulations differed between tissues as revealed by the comparison of metabolite networks based on correlations between compounds. This work stressed the role of specific tissues less studied than pericarp but that impact fruit organoleptic quality including its shape and taste, and fruit processing quality. PMID: 31075946 [PubMed]

Related Articles Comparison of Bi- and Tri-Linear PLS Models for Variable Selection in Metabolomic Time-Series Experiments. Metabolites. 2019 May 09;9(5): Authors: Gao Q, Dragsted LO, Ebbels T Abstract Metabolomic studies with a time-series design are widely used for discovery and validation of biomarkers. In such studies, changes of metabolic profiles over time under different conditions (e.g., control and intervention) are compared, and metabolites responding differently between the conditions are identified as putative biomarkers. To incorporate time-series information into the variable (biomarker) selection in partial least squares regression (PLS) models, we created PLS models with different combinations of bilinear/trilinear X and group/time response dummy Y. In total, five PLS models were evaluated on two real datasets, and also on simulated datasets with varying characteristics (number of subjects, number of variables, inter-individual variability, intra-individual variability and number of time points). Variables showing specific temporal patterns observed visually and determined statistically were labelled as discriminating variables. Bootstrapped-VIP scores were calculated for variable selection and the variable selection performance of five PLS models were assessed based on their capacity to correctly select the discriminating variables. The results showed that the bilinear PLS model with group × time response as dummy Y provided the highest recall (true positive rate) of 83-95% with high precision, independent of most characteristics of the datasets. Trilinear PLS models tend to select a small number of variables with high precision but relatively high false negative rate (lower power). They are also less affected by the noise compared to bilinear PLS models. In datasets with high inter-individual variability, bilinear PLS models tend to provide higher recall while trilinear models tend to provide higher precision. Overall, we recommend bilinear PLS with group x time response Y for variable selection applications in metabolomics intervention time series studies. PMID: 31075899 [PubMed]

Related Articles Acute Tumor Transition Angle on Computed Tomography Predicts Chromosomal Instability Status of Primary Gastric Cancer: Radiogenomics Analysis from TCGA and Independent Validation. Cancers (Basel). 2019 May 09;11(5): Authors: Lai YC, Yeh TS, Wu RC, Tsai CK, Yang LY, Lin G, Kuo MD Abstract Chromosomal instability (CIN) of gastric cancer is correlated with distinct outcomes. This study aimed to investigate the role of computed tomography (CT) imaging traits in predicting the CIN status of gastric cancer. We screened 443 patients in the Cancer Genome Atlas gastric cancer cohort to filter 40 patients with complete CT imaging and genomic data as the training cohort. CT imaging traits were subjected to logistic regression to select independent predictors for the CIN status. For the validation cohort, we prospectively enrolled 18 gastric cancer patients for CT and tumor genomic analysis. The imaging predictors were tested in the validation cohort using receiver operating characteristic curve (ROC) analysis. Thirty patients (75%) in the training cohort and 9 patients (50%) in the validation cohort had CIN subtype gastric cancers. Smaller tumor diameter (p = 0.017) and acute tumor transition angle (p = 0.045) independently predict CIN status in the training cohort. In the validation cohort, acute tumor transition angle demonstrated the highest accuracy, sensitivity, and specificity of 88.9%, 88.9%, and 88.9%, respectively, and areas under ROC curve of 0.89. In conclusion, this pilot study showed acute tumor transition angle on CT images may predict the CIN status of gastric cancer. PMID: 31075839 [PubMed]