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metabolomics
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metabolomics; +16 new citations
16 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 2019/09/04PubMed 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.
metabolomics; +16 new citations
16 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 2019/09/04PubMed 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.
Chronic kidney disease: Biomarker diagnosis to therapeutic targets.
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Chronic kidney disease: Biomarker diagnosis to therapeutic targets.
Clin Chim Acta. 2019 Aug 30;:
Authors: Wang YN, Ma SX, Chen YY, Chen L, Liu BL, Liu QQ, Zhao YY
Abstract
Chronic kidney disease (CKD), characterized as renal dysfunction, is recognized as a major public health problem with high morbidity and mortality worldwide. Unfortunately, there are no obvious clinical symptoms in early stage disease until severe damage has occurred. Further complicating early diagnosis and treatment is the lack of sensitive and specific biomarkers. As such, novel biomarkers are urgently needed. Metabolomics has shown an increasing potential for identifying underlying disease mechanisms, facilitating clinical diagnosis and developing pharmaceutical treatments for CKD. Recent advances in metabolomics revealed that CKD was closely associated with the dysregulation of numerous metabolites, such as amino acids, lipids, nucleotides and glycoses, that might be exploited as potential biomarkers. In this review, we summarize recent metabolomic applications based on animal model studies and in patients with CKD and highlight several biomarkers that may play important roles in diagnosis, intervention and development of new therapeutic strategies.
PMID: 31476302 [PubMed - as supplied by publisher]
Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation.
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Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation.
J Am Heart Assoc. 2019 Sep 03;8(17):e012809
Authors: Choi J, Shoaib M, Yin T, Nayyar G, Shinozaki K, Stevens JF, Becker LB, Kim J
Abstract
Background Cardiac arrest (CA) has been a leading cause of death for many decades. Despite years of research, we still do not understand how each organ responds to the reintroduction of blood flow after prolonged CA. Following changes in metabolites of individual organs after CA and resuscitation gives context to the efficiency and limitations of current resuscitation protocols. Methods and Results Adult male Sprague-Dawley rats were arbitrarily assigned into 3 groups: control, 20 minutes of CA, or 20 minutes of CA followed by 30 minutes of cardiopulmonary bypass resuscitation. The rats were euthanized by decapitation to harvest brain, heart, kidney, and liver tissues. The obtained tissue samples were analyzed by ultra-high-performance liquid chromatography-high-accuracy mass spectrometry for comprehensive metabolomics evaluation. After resuscitation, the brain showed decreased glycolysis metabolites and fatty acids and increased amino acids compared with control. Similarly, the heart displayed alterations mostly in amino acids. The kidney showed decreased amino acid and fatty acid pools with severely increased tricarboxylic acid cycle metabolites following resuscitation, while the liver showed minimal alterations with slight changes in the lipid pool. Each tissue has a distinct pattern of metabolite changes after ischemia/reperfusion. Furthermore, resuscitation worsens the metabolic dysregulation in the brain and kidney, while it normalizes metabolism in the heart. Conclusions Developing metabolic profiles using a global metabolome analysis identifies the variable nature of metabolites in individual organs after CA and reperfusion, establishing a stark contrast between the normalized heart and liver and the exacerbated brain and kidney, only after the reestablishment of blood circulation.
PMID: 31475603 [PubMed - in process]
The Diversity of Nutritional Metabolites: Origin, Dissection, and Application in Crop Breeding.
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The Diversity of Nutritional Metabolites: Origin, Dissection, and Application in Crop Breeding.
Front Plant Sci. 2019;10:1028
Authors: Fang C, Luo J, Wang S
Abstract
The chemical diversity of plants is very high, and plant-based foods provide almost all the nutrients necessary for human health, either directly or indirectly. With advancements in plant metabolomics studies, the concept of nutritional metabolites has been expanded and updated. Because the concentration of many nutrients is usually low in plant-based foods, especially those from crops, metabolome-assisted breeding techniques using molecular markers associated with the synthesis of nutritional metabolites have been developed and used to improve nutritional quality of crops. Here, we review the origins of the diversity of nutrient metabolites from a genomic perspective and the role of gene duplication and divergence. In addition, we systematically review recent advances in the metabolomic and genetic basis of metabolite production in major crops. With the development of genome sequencing and metabolic detection technologies, multi-omic integrative analysis of genomes, transcriptomes, and metabolomes has greatly facilitated the deciphering of the genetic basis of metabolic pathways and the diversity of nutrient metabolites. Finally, we summarize the application of nutrient diversity in crop breeding and discuss the future development of a viable alternative to metabolome-assisted breeding techniques that can be used to improve crop nutrient quality.
PMID: 31475024 [PubMed]
Distinct Morphological, Physiological, and Biochemical Responses to Light Quality in Barley Leaves and Roots.
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Distinct Morphological, Physiological, and Biochemical Responses to Light Quality in Barley Leaves and Roots.
Front Plant Sci. 2019;10:1026
Authors: Klem K, Gargallo-Garriga A, Rattanapichai W, Oravec M, Holub P, Veselá B, Sardans J, Peñuelas J, Urban O
Abstract
Light quality modulates plant growth, development, physiology, and metabolism through a series of photoreceptors perceiving light signal and related signaling pathways. Although the partial mechanisms of the responses to light quality are well understood, how plants orchestrate these impacts on the levels of above- and below-ground tissues and molecular, physiological, and morphological processes remains unclear. However, the re-allocation of plant resources can substantially adjust plant tolerance to stress conditions such as reduced water availability. In this study, we investigated in two spring barley genotypes the effect of ultraviolet-A (UV-A), blue, red, and far-red light on morphological, physiological, and metabolic responses in leaves and roots. The plants were grown in growth units where the root system develops on black filter paper, placed in growth chambers. While the growth of above-ground biomass and photosynthetic performance were enhanced mainly by the combined action of red, blue, far-red, and UV-A light, the root growth was stimulated particularly by supplementary far-red light to red light. Exposure of plants to the full light spectrum also stimulates the accumulation of numerous compounds related to stress tolerance such as proline, secondary metabolites with antioxidative functions or jasmonic acid. On the other hand, full light spectrum reduces the accumulation of abscisic acid, which is closely associated with stress responses. Addition of blue light induced accumulation of γ-aminobutyric acid (GABA), sorgolactone, or several secondary metabolites. Because these compounds play important roles as osmolytes, antioxidants, UV screening compounds, or growth regulators, the importance of light quality in stress tolerance is unequivocal.
PMID: 31475023 [PubMed]
Erratum to "Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder" [Eur Urol Focus 2018;4:907-915].
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Erratum to "Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder" [Eur Urol Focus 2018;4:907-915].
Eur Urol Focus. 2019 Aug 29;:
Authors: Piyarathna DWB, Rajendiran TM, Putluri V, Vantaku V, Soni T, von Rundstedt FC, Donepudi SR, Jin F, Maity S, Ambati CR, Dong J, Gödde D, Roth S, Störkel S, Degener S, Michailidis G, Lerner SP, Pennathur S, Lotan Y, Coarfa C, Sreekumar A, Putluri N
PMID: 31474581 [PubMed - as supplied by publisher]
Proton Transfer Reaction Mass Spectrometry for Plant Metabolomics.
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Proton Transfer Reaction Mass Spectrometry for Plant Metabolomics.
Trends Plant Sci. 2019 Aug 29;:
Authors: Majchrzak T, Wojnowski W, Wasik A
PMID: 31474555 [PubMed - as supplied by publisher]
Metabolomics study on the therapeutic effect of traditional Chinese medicine Xue-Fu-Zhu-Yu decoction in coronary heart disease based on LC-Q-TOF/MS and GC-MS analysis.
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Metabolomics study on the therapeutic effect of traditional Chinese medicine Xue-Fu-Zhu-Yu decoction in coronary heart disease based on LC-Q-TOF/MS and GC-MS analysis.
Drug Metab Pharmacokinet. 2019 Aug 02;:
Authors: Yi M, Li Q, Zhao Y, Nie S, Wu N, Wang D
Abstract
The present study aims is to investigate the metabolic mechanism of Xue-Fu-Zhu-Yu decoction (XFZYD) in the treatment of blood-stasis syndrome in Coronary Heart Disease (CHD). To that end, 30 CHD patients with Blood-Stasis Syndrome (BSS) and 20 healthy subjects were enrolled. LC-Q-TOF/MS analysis determined that in comparison between CHD with BSS patients (Group A) and healthy subjects (Group C), 59 significantly differential metabolites in the positive mode and 18 significantly differential metabolites in the negative mode. The metabolite constituents in the plasma of 30 CHD with BSS patients before (group A) and after 30 days of treatment (Group B), and 20 healthy subjects (Group C) were analyzed using LC-Q-TOF/MS and GC-MS. Based on multivariate statistical analysis (PCA, PLS-DA and OPLS-DA), we determined 69 differential metabolites. The levels of hemorheology indexes were significantly down-regulated after treatment. Metabolic pathway attribution analysis showed that lipid metabolism, amino acid metabolism and bile acid metabolism pathways are involved. Our study identifies the metabolic networks of CHD and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effect of XFZYC on CHD.
PMID: 31474470 [PubMed - as supplied by publisher]
Characterizing the metabotype and its persistency in lactating Holstein cows: An approach toward metabolic efficiency measures.
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Characterizing the metabotype and its persistency in lactating Holstein cows: An approach toward metabolic efficiency measures.
J Dairy Sci. 2019 Jul;102(7):6559-6570
Authors: Derno M, Nürnberg G, Kuhla B
Abstract
The variation in feed efficiency among dairy cows is due to differences in fermentation and digestion characteristics, but recent studies have suggested that various aspects of postabsorptive metabolic processes including heat production or the metabolizable energy for maintenance are more crucial. Thus, metabolic efficiency largely determines feed efficiency, but whether divergent feed efficient cows differ in O2 consumption and metabolic CO2 production, directly determining the metabolic rate has not been investigated. Therefore, the objective of the present study was to determine whether variation in ME intake (MEI), O2 consumption, and metabolic CO2 production account for the variation in metabolic efficiency of dairy cows and whether this effect persists across the lactation cycle. Eighteen cows with different German breeding value functional herd life were kept in freestalls with ad libitum access to a total mixed ration that was kept constant in composition throughout the first lactation. Cows were blood sampled and weighed at wk 5, 13, and 42 postpartum (pp) and transferred into respiration chambers. Animals were retrospectively clustered according to MEI, O2 consumption, and metabolic CO2 production, each normalized to metabolic body weight (mBW). Cluster analysis revealed 9 high metabolically efficient (high-Meff) and 9 low metabolically efficient cows. The high-Meff cows had greater MEI and feed conversion efficiency, produced less metabolic CO2 and methane, had a stronger negative energy balance, and tended to have a lower metabolic respiratory quotient. Further, high-Meff cows had lower residual MEI, less heat energy loss, and lower plasma glucose concentrations, but used a greater portion of body reserves instead of feed energy for milk synthesis, particularly at wk 5 and 13 pp. However, these group differences did not persist by wk 42 pp. Cow groups were not different in O2 consumption, milk yield, metabolizable energy for maintenance, or the efficiency of tissue utilization for milk synthesis, but high-Meff cows tended to have the lower German relative breeding value functional herd life, indicating a link between metabolic performance and productive lifespan. In conclusion, the use of a clustering approach involving MEI/mBW, O2/mBW, and CO2/mBW seems to be a promising method to differentiate cows with divergent metabolic efficiency but does not allow identifying an individual metabotype that persists across the whole lactation cycle.
PMID: 31103305 [PubMed - indexed for MEDLINE]
A NMR-Based Metabonomics Approach to Determine Protective Effect of a Combination of Multiple Components Derived from Naodesheng on Ischemic Stroke Rats.
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A NMR-Based Metabonomics Approach to Determine Protective Effect of a Combination of Multiple Components Derived from Naodesheng on Ischemic Stroke Rats.
Molecules. 2019 May 13;24(9):
Authors: Luo L, Kang J, He Q, Qi Y, Chen X, Wang S, Liang S
Abstract
Naodesheng (NDS) is a widely used traditional Chinese medicine (TCM) prescription for the treatment of ischemic stroke. A combination of 10 components is derived from NDS. They are: Notoginsenoside R1, ginsenoside Rg1, ginsenoside b1, ginsenoside Rd, hydroxysafflor yellow A, senkyunolide I, puerarin, daidzein, vitexin, and ferulic acid. This study aimed to investigate the protective effect of the ten-component combination derived from NDS (TCNDS) on ischemic stroke rats with a middle cerebral artery occlusion (MCAO) model by integrating an NMR-based metabonomics approach with biochemical assessment. Our results showed that TCNDS could improve neurobehavioral function, decrease the cerebral infarct area, and ameliorate pathological features in MCAO model rats. In addition, TCNDS was found to decrease plasma lactate dehydrogenase (LDH) and malondialdehyde (MDA) production and increase plasma superoxide dismutase (SOD) production. Furthermore, 1H-NMR metabonomic analysis indicated that TCNDS could regulate the disturbed metabolites in the plasma, urine, and brain tissue of MCAO rats, and the possible mechanisms were involved oxidative stress, energy metabolism, lipid metabolism, amino acid metabolism, and inflammation. Correlation analysis were then performed to further confirm the metabolites involved in oxidative stress. Correlation analysis showed that six plasma metabolites had high correlations with plasma LDH, MDA, and SOD. This study provides evidence that an NMR-based metabonomics approach integrated with biochemical assessment can help to better understand the underlying mechanisms as well as the holistic effect of multiple compounds from TCM.
PMID: 31086027 [PubMed - indexed for MEDLINE]
Fucose-Functionalized Precision Glycomacromolecules Targeting Human Norovirus Capsid Protein.
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Fucose-Functionalized Precision Glycomacromolecules Targeting Human Norovirus Capsid Protein.
Biomacromolecules. 2018 09 10;19(9):3714-3724
Authors: Bücher KS, Yan H, Creutznacher R, Ruoff K, Mallagaray A, Grafmüller A, Dirks JS, Kilic T, Weickert S, Rubailo A, Drescher M, Schmidt S, Hansman G, Peters T, Uetrecht C, Hartmann L
Abstract
Norovirus infection is the major cause of nonbacterial gastroenteritis in humans and has been the subject of numerous studies investigating the virus's biophysical properties and biochemical function with the aim of deriving novel and highly potent entry inhibitors to prevent infection. Recently, it has been shown that the protruding P domain dimer (P-dimer) of a GII.10 Norovirus strain exhibits two new binding sites for l-fucose in addition to the canonical binding sites. Thus, these sites provide a novel target for the design of multivalent fucose ligands as entry inhibitors of norovirus infections. In this current study, a first generation of multivalent fucose-functionalized glycomacromolecules was synthesized and applied as model structures to investigate the potential targeting of fucose binding sites in human norovirus P-dimer. Following previously established solid phase polymer synthesis, eight precision glycomacromolecules varying in number and position of fucose ligands along an oligo(amidoamine) backbone were obtained and then used in a series of binding studies applying native MS, NMR, and X-ray crystallography. We observed only one fucose per glycomacromolecule binding to one P-dimer resulting in similar binding affinities for all fucose-functionalized glycomacromolecules, which based on our current findings we attribute to the overall size of macromolecular ligands and possibly to steric hindrance.
PMID: 30071731 [PubMed - indexed for MEDLINE]
Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults.
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Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults.
Physiol Rep. 2018 07;6(14):e13799
Authors: Hulston CJ, Woods RM, Dewhurst-Trigg R, Parry SA, Gagnon S, Baker L, James LJ, Markey O, Martin NRW, Ferguson RA, van Hall G
Abstract
Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.5 ± 0.6 kg/m2 ) and 8 obese (33.6 ± 1.2 kg/m2 ) physically active young adults participated in a study that determined muscle protein synthesis and intracellular signaling at rest and following an acute bout of resistance exercise. Mixed muscle protein synthesis was determined by combining stable isotope tracer ([13 C6 ]phenylalanine) infusion with serial biopsies of the vastus lateralis. A unilateral leg resistance exercise model was adopted so that resting and postexercise measurements of muscle protein synthesis could be obtained simultaneously. Obesity was associated with higher basal levels of serum insulin (P < 0.05), plasma triacylglycerol (P < 0.01), plasma cholesterol (P < 0.01), and plasma CRP (P < 0.01), as well as increased insulin resistance determined by HOMA-IR (P < 0.05). However, resting and postexercise rates of muscle protein synthesis were not significantly different between lean and obese participants (P = 0.644). Furthermore, resistance exercise stimulated muscle protein synthesis (~50% increase) in both groups (P < 0.001), with no difference between lean and obese (P = 0.809). Temporal increases in the phosphorylation of intracellular signaling proteins (AKT/4EBP1/p70S6K) were observed within the exercised leg (P < 0.05), with no differences between lean and obese. These findings suggest a normal anabolic response to muscle loading in obese young adults.
PMID: 30009507 [PubMed - indexed for MEDLINE]
Pseudoqc: A Regression-Based Simulation Software for Correction and Normalization of Complex Metabolomics and Proteomics Datasets.
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Pseudoqc: A Regression-Based Simulation Software for Correction and Normalization of Complex Metabolomics and Proteomics Datasets.
Proteomics. 2019 Aug 31;:e1900264
Authors: Wang S, Yang H
Abstract
Various types of unwanted and uncontrollable signal variations in mass spectrometry (MS)-based metabolomics and proteomics datasets severely disturb the accuracies of metabolite and protein profiling. Therefore, pooled quality control (QC) samples are often employed in quality management processes, which are indispensable to the success of metabolomics and proteomics experiments, especially in high-throughput cases and long-term projects. However, data consistency and QC sample stability are still difficult to guarantee because of the experimental operation complexity and differences between experimenters. To make things worse, numerous proteomics projects do not take QC samples into consideration at the beginning of experimental design. Herein, we present a powerful and interactive web-based software, named pseudoQC, to simulate QC sample data for actual metabolomics and proteomics datasets using four different machine learning-based regression methods. The simulated data are used for correction and normalization of the two published datasets, and the obtained results suggest that nonlinear regression methods perform better than linear ones. Additionally, the above software is available as a web-based graphical user interface (GUI) and can be utilized by scientists without a bioinformatics background. pseudoQC is open-source software and freely available at https://www.omicsolution.org/wukong/pseudoQC/. This article is protected by copyright. All rights reserved.
PMID: 31474000 [PubMed - as supplied by publisher]
Resveratrol-mediated glycemic regulation is blunted by curcumin and is associated to modulation of gut microbiota.
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Resveratrol-mediated glycemic regulation is blunted by curcumin and is associated to modulation of gut microbiota.
J Nutr Biochem. 2019 Jul 30;72:108218
Authors: Sreng N, Champion S, Martin JC, Khelaifia S, Christensen JE, Padmanabhan R, Azalbert V, Blasco-Baque V, Loubieres P, Pechere L, Landrier JF, Burcelin R, Sérée E
Abstract
The polyphenols resveratrol (RSV) and curcumin (Cur) are phytoalexines and natural antibiotics with numerous pharmacological functions and metabolic impacts. Recent evidences show a broad control of gut microbiota by polyphenols which could influence glycemic regulation. The aim of this work is to estimate the respective effect of RSV and Cur alone or in association on the control of glycemia and on gut microbiota. A 5-week chronic treatment of hyperglycemic mice with RSV and/or Cur resulted in a differential effect on glucose tolerance test and modified gut microbiome. We precisely identified groups of bacteria representing a specific signature of the glycemic effect of RSV. Inferred metagenomic analysis and metabolic pathway prediction showed that the sulfur and branched-chain amino-acid (BCAA) metabolic activities are tightly correlated with the efficacy of RSV for the control of glycaemia. The impact on BCAA metabolism was further validated by serum metabolomics analysis. Altogether, we show that polyphenols specifically impact gut microbiota and corresponding metabolic functions which could be responsible for their therapeutic role.
PMID: 31473511 [PubMed - as supplied by publisher]
A metabolomics study on effects of polyaromatic compounds in oil sand extracts on the respiratory, hepatic and nervous systems using three human cell lines.
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A metabolomics study on effects of polyaromatic compounds in oil sand extracts on the respiratory, hepatic and nervous systems using three human cell lines.
Environ Res. 2019 Aug 19;178:108680
Authors: Sarma SN, Kimpe LE, Doyon VC, Blais JM, Chan HM
Abstract
Polyaromatic compounds (PACs) are by-products of combustion and are the major pollutants from the oil and gas industry. However, the mechanism of PACs induced toxicity still remains elusive. The aim of this study was to elucidate the effects of a typical mixture of PACs found in oil sand extract (OSE) on the respiratory, hepatic and nervous systems in humans using in vitro cell culture models followed by non-targeted metabolomics analysis. OSE collected from Alberta, Canada was fractionated into PAC and alkane fractions, and their effects after 24 h exposure on the cell viability measured by MTT assay in three human cell lines (A549, HepG2, and SK-N-SH) were studied. The PAC fractions showed significant dose-dependent cytotoxicity. A549 cells showed the highest sensitivity to OSE extracts, followed by SK-N-SH and HepG2. In contrast, the alkane fractions showed no effects on cell viability. The three human cell lines were further exposed with the PACs at 10% and 20% lethal concentration for 24 h. Metabolomics analysis of the cell extracts indicated that PACs treatments showed different disruptions on possible metabolic pathways on the three cell lines. PACs altered the sex steroid hormone metabolism and regulated the levels of leukotrienes metabolites in all three cell types. The amino acids L-cysteine, L-glutamine, L-tyrosine that are known to cause respiratory effects were significantly up-regulated in A549 cells. The PACs treated HepG2 cells showed down-regulation in metabolites responsible for the inflammatory mediation. Treatment of the differentiated SK-N-SH cells showed up-regulated metabolites involved with butanoate, fatty acid, and pyrimidine metabolism. Leukotriene metabolites were found to be significantly increased in all PACs treated cells. In conclusion, our results showed that PACs in OSE can alter the metabolism of the human lung, liver and neuronal cells and may induce toxicity in multiple target organs.
PMID: 31473503 [PubMed - as supplied by publisher]
Dynamic Metabolomics for Engineering Biology: Accelerating Learning Cycles for Bioproduction.
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Dynamic Metabolomics for Engineering Biology: Accelerating Learning Cycles for Bioproduction.
Trends Biotechnol. 2019 Aug 28;:
Authors: Vavricka CJ, Hasunuma T, Kondo A
Abstract
Metabolomics is a powerful tool to rationally guide the metabolic engineering of synthetic bioproduction pathways. Current reports indicate great potential to further develop metabolomics-directed synthetic bioproduction. Advanced mass metabolomics methods including isotope flux analysis, untargeted metabolomics, and system-wide approaches are assisting the characterization of metabolic pathways and enabling the biosynthesis of more complex products. More importantly, a design, build, test, and learn (DBTL) cycle is accelerating synthetic biology research and is highly compatible with metabolomics data to further expand bioproduction capability. However, learning processes are currently the weakest link in this workflow. Therefore, guidelines for the development of metabolic learning processes are proposed based on bioproduction examples. Linking dynamic mass spectrometry (MS) methodologies together with automated learning workflows is encouraged.
PMID: 31473013 [PubMed - as supplied by publisher]
Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids.
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Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids.
Microbiome. 2019 Aug 31;7(1):126
Authors: Wang S, Martins R, Sullivan MC, Friedman ES, Misic AM, El-Fahmawi A, De Martinis ECP, O'Brien K, Chen Y, Bradley C, Zhang G, Berry ASF, Hunter CA, Baldassano RN, Rondeau MP, Beiting DP
Abstract
BACKGROUND: The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn's disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease.
RESULTS: We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens, was associated with diet-induced remission in human pediatric Crohn's disease.
CONCLUSIONS: These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn's disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets.
PMID: 31472697 [PubMed - in process]
Study of metabolic disorders associated with BDE-47 exposure in Drosophila model by MS-based metabolomics.
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Study of metabolic disorders associated with BDE-47 exposure in Drosophila model by MS-based metabolomics.
Ecotoxicol Environ Saf. 2019 Aug 28;184:109606
Authors: Ji F, Wei J, Luan H, Li M, Cai Z
Abstract
Epidemiological and animal studies have revealed a possible linkage between 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) exposure and neurodegenerative disease such as Parkinson's disease (PD). However, whether or how BDE-47 would affect the PD progression remains unclear. Here, we carried out a metabolomics study based on liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to investigate the possible contribution of BDE-47 exposure to PD progression in Drosophila (fly) model. Transgenic PD flies were exposed to BDE-47 through diet for 30 days. Global metabolomic analysis identified 48 altered metabolites after the exposure. These metabolites were mainly involved in tryptophan metabolism, phenylalanine metabolism, purine metabolism, and alanine, aspartate and glutamate metabolism. Further, by quantifying metabolites of interest using LC-MS/MS, we confirmed that the formation of neuro-protector kynurenic acid was slowed down while the formation of neurotoxin 3-hydroxy-kynurenine was speeded up on the 20th exposure day. Moreover, the levels of SAM/SAH (an index of methylation potential) and GSH/GSSG (an indicator of oxidative stress) were found to decrease on the 30th exposure day. Our results suggest that BDE-47 could induce imbalance of kynurenine metabolism and methylation potential, and oxidative stress, which might further accelerate PD progression.
PMID: 31472382 [PubMed - as supplied by publisher]