Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Multi-omics signature of brain amyloid deposition in asymptomatic individuals at-risk for Alzheimer's disease: The INSIGHT-preAD study.

Sun, 08/09/2019 - 12:44
Related Articles Multi-omics signature of brain amyloid deposition in asymptomatic individuals at-risk for Alzheimer's disease: The INSIGHT-preAD study. EBioMedicine. 2019 Sep 03;: Authors: Xicota L, Ichou F, Lejeune FX, Colsch B, Tenenhaus A, Leroy I, Fontaine G, Lhomme M, Bertin H, Habert MO, Epelbaum S, Dubois B, Mochel F, Potier MC, INSIGHT study group Abstract BACKGROUND: One of the biggest challenge in Alzheimer's disease (AD) is to identify pathways and markers of disease prediction easily accessible, for prevention and treatment. Here we analysed blood samples from the INveStIGation of AlzHeimer's predicTors (INSIGHT-preAD) cohort of elderly asymptomatic individuals with and without brain amyloid load. METHODS: We performed blood RNAseq, and plasma metabolomics and lipidomics using liquid chromatography-mass spectrometry on 48 individuals amyloid positive and 48 amyloid negative (SUVr cut-off of 0·7918). The three data sets were analysed separately using differential gene expression based on negative binomial distribution, non-parametric (Wilcoxon) and parametric (correlation-adjusted Student't) tests. Data integration was conducted using sparse partial least squares-discriminant and principal component analyses. Bootstrap-selected top-ten features from the three data sets were tested for their discriminant power using Receiver Operating Characteristic curve. Longitudinal metabolomic analysis was carried out on a subset of 22 subjects. FINDINGS: Univariate analyses identified three medium chain fatty acids, 4-nitrophenol and a set of 64 transcripts enriched for inflammation and fatty acid metabolism differentially quantified in amyloid positive and negative subjects. Importantly, the amounts of the three medium chain fatty acids were correlated over time in a subset of 22 subjects (p < 0·05). Multi-omics integrative analyses showed that metabolites efficiently discriminated between subjects according to their amyloid status while lipids did not and transcripts showed trends. Finally, the ten top metabolites and transcripts represented the most discriminant omics features with 99·4% chance prediction for amyloid positivity. INTERPRETATION: This study suggests a potential blood omics signature for prediction of amyloid positivity in asymptomatic at-risk subjects, allowing for a less invasive, more accessible, and less expensive risk assessment of AD as compared to PET studies or lumbar puncture. FUND: Institut Hospitalo-Universitaire and Institut du Cerveau et de la Moelle Epiniere (IHU-A-ICM), French Ministry of Research, Fondation Alzheimer, Pfizer, and Avid. PMID: 31492558 [PubMed - as supplied by publisher]

Physiological and metabolomics analyses of young and old leaves from wild and cultivated soybean seedlings under low-nitrogen conditions.

Sun, 08/09/2019 - 12:44
Related Articles Physiological and metabolomics analyses of young and old leaves from wild and cultivated soybean seedlings under low-nitrogen conditions. BMC Plant Biol. 2019 Sep 06;19(1):389 Authors: Liu Y, Li M, Xu J, Liu X, Wang S, Shi L Abstract BACKGROUND: It is critical to study the low nitrogen tolerance in wild soybean with extensive genetic diversity for improving cultivated soybean nitrogen use efficiency. Focusing on plant young and old leaves could provide new insights to low nitrogen tolerance research. This study compared the low nitrogen group with the control group on physiological and metabolomics changes in young and old leaves, respectively, then analyzed and compared the differences of these changes between cultivated and wild soybean. This study aimed to provide a theoretical basis for the molecular mechanism of soybean low nitrogen stress tolerance. RESULTS: Wild soybean was less affected by low-nitrogen stress than cultivated soybean as assessed by plant biomass paraments, total carbon content and total nitrogen content. Gas-exchange coefficients and chlorophylls contents maintained relatively stable in wild soybean young leaves, but opposite in cultivated soybean. Wild soybean young leaves also increased the transport of beneficial ions, such as B3+, Fe3+, Mn2+, H2PO4- and C2O42-. In wild soybean old leaves, the nitrogen metabolism pathway was significant enhanced, especially the aspartic acid and GABA metabolisms. While in cultivated soybean, the nitrogen metabolism decreased obviously in young leaves but had no significant change in old leaves. The phenylpropanoid metabolism pathway was also activated in wild soybean. Contrary to cultivated soybeans, wild soybean tricarboxylic acid cycle and carbon metabolism including polyols and organic acids consolidated in old leaves and maintained a relative normal state in young leaves. These strategies could improve the antioxidant and N-fixation capacity in wild soybean. CONCLUSION: The survival and growth of wild soybean under low nitrogen stress conditions relied on physiological adjustments and metabolic changes that occurred at the cellular level. Compared with cultivated soybean, wild soybean young leaves could maintain a relatively normal growth mainly owing to a significant enhancement of key amino acids and nonprotein nitrogen metabolism in old leaves, especially aspartic acid, proline metabolism which provided basis for nitrogen reutilization from old leaves to young leaves. Consolidating the tricarboxylic acid cycle, intensifying phenylpropanoid metabolism, and accumulating more polyols and organic acids also had positive effect on it. PMID: 31492111 [PubMed - in process]

Analysis of widely targeted metabolites of the euhalophyte Suaeda salsa under saline conditions provides new insights into salt tolerance and nutritional value in halophytic species.

Sun, 08/09/2019 - 12:44
Related Articles Analysis of widely targeted metabolites of the euhalophyte Suaeda salsa under saline conditions provides new insights into salt tolerance and nutritional value in halophytic species. BMC Plant Biol. 2019 Sep 06;19(1):388 Authors: Li Q, Song J Abstract BACKGROUND: Suaeda salsa L. (S. salsa) is an annual euhalophyte with high salt tolerance and high value as an oil crop, traditional Chinese medicine and vegetable. However, there are few comprehensive studies on the metabolomics of S. salsa under saline conditions. RESULTS: Seedlings of S. salsa were cultured with 0, 200 and 500 mM NaCl for two days. Then, widely targeted metabolites were detected with ultra performance liquid chromatography and tandem mass spectrometry. A total of 639 metabolites were annotated. Among these, 253 metabolites were differential metabolites. Salt treatment increased the content of certain metabolites, such as nucleotide and its derivates, organic acids, the content of amino acids, lipids such as α-linolenic acid, and certain antioxidants such as quercetin. These substances may be correlated to osmotic tolerance, increased antioxidant activity, and medical and nutritional value in the species. CONCLUSION: This study comprehensively analyzed the metabolic response of S. salsa under salinity from the perspective of omics, and provides an important theoretical basis for understanding salt tolerance and evaluating nutritional value in the species. PMID: 31492100 [PubMed - in process]

Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis.

Sun, 08/09/2019 - 12:44
Related Articles Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis. Int J Mol Sci. 2019 Sep 05;20(18): Authors: Salic K, Gart E, Seidel F, Verschuren L, Caspers M, van Duyvenvoorde W, Wong KE, Keijer J, Bobeldijk-Pastorova I, Wielinga PY, Kleemann R Abstract Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr -/-.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (-17%) and hepatic steatosis (-22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD. PMID: 31491949 [PubMed - in process]

metabolomics; +19 new citations

Sat, 07/09/2019 - 15:36
19 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 2019/09/07PubMed 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; +19 new citations

Sat, 07/09/2019 - 12:35
19 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 2019/09/07PubMed 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.

Analysis of metabolites in chardonnay dry white wine with various inactive yeasts by 1H NMR spectroscopy combined with pattern recognition analysis.

Fri, 06/09/2019 - 15:29
Related Articles Analysis of metabolites in chardonnay dry white wine with various inactive yeasts by 1H NMR spectroscopy combined with pattern recognition analysis. AMB Express. 2019 Sep 05;9(1):140 Authors: Hu B, Cao Y, Zhu J, Xu W, Wu W Abstract The study aimed to investigate the effect of five inactive yeasts on the metabolites of Chardonnay dry white wines vinified in 2016 in Shacheng Manor Wine Co. Ltd., Hebei province, China. In this research, proton nuclear magnetic resonance (NMR) spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) were applied to identify and discriminate the different wine products. The results of principle component analysis (PCA) showed that there was significant difference between the metabolites of sample wines with different inactive yeasts, among them, the content of polyols, organic acids, amino acids and choline was notably influenced. The results of partial least squares discrimination analysis (PLS-DA) confirmed that the metabolites contributed to the discrimination of the wines were 2,3-butanediol, ethyl acetate, malic acid, valine, succinic acid, lactic acid, tartaric acid, glycerol, gallic acid, choline, proline, and alanine. PMID: 31486932 [PubMed]

The Design and Application of an Appropriate Parkinson's Disease Animal Model in Regenerative Medicine.

Fri, 06/09/2019 - 15:29
Related Articles The Design and Application of an Appropriate Parkinson's Disease Animal Model in Regenerative Medicine. Adv Exp Med Biol. 2019 Sep 05;: Authors: Larijani B, Goodarzi P, Payab M, Tayanloo-Beik A, Sarvari M, Gholami M, Gilany K, Nasli-Esfahani E, Yarahmadi M, Ghaderi F, Arjmand B Abstract OBJECTIVES: Aging as an inevitable and complex physiological process occurs through a progressive decrease in the potential of tissue regeneration. Given the increasing global outbreak of aging and age-related disorders, it is important to control this phenomenon. Parkinson's disease (one of the age-related neurodegenerative and progressive disorders) resulted from predominant dopaminergic neurons deficiency. Usual Parkinson's disease treatments just can lead to symptomatically relieving. Recently, cell therapy and regenerative medicine a great promise in the treatment of several types of disorders including Parkinson's disease. Herein, before starting clinical trials, preclinical studies should be performed to answer some fundamental questions about the safety and efficacy of various treatments. Additionally, developing a well-designed and approved study is required to provide an appropriate animal model with strongly reliable validation methods. Hereupon, this review will discuss about the design and application of an appropriate Parkinson's disease animal model in regenerative medicine. EVIDENCE ACQUISITION: In order to conduct the present review, numbers of Parkinson's disease preclinical studies, as well as literatures related to the animal modeling, were considered. RESULTS: Appropriate animal models which approved by related authorize committees should have a high similarity to humans from anatomical, physiological, behavioral, and genetic characteristics view of point. CONCLUSION: It is concluded that animal studies before starting clinical trials have an important role in answering the crucial questions about the various treatments safety and efficacy. Therein, it is recommended that all of animal modeling stages be assessed by animal ethics and welfare guidelines and also evaluated by different validation tests. However, it is better to find some alternatives to replacement, refinement, and, reduction of animals. Nowadays, some novel technologies such as using imaging methods have been introduced. PMID: 31485993 [PubMed - as supplied by publisher]

Generation of a Small Library of Natural Products Designed to Cover Chemical Space Inexpensively.

Fri, 06/09/2019 - 15:29
Related Articles Generation of a Small Library of Natural Products Designed to Cover Chemical Space Inexpensively. Pharm Front. 2019;1(1):e190005 Authors: O'Hagan S, Kell DB Abstract Natural products space includes at least 200,000 compounds and the structures of most of these compounds are available in digital format. Previous analyses showed (i) that although they were capable of taking up synthetic pharmaceutical drugs, such exogenous molecules were likely the chief 'natural' substrates in the evolution of the transporters used to gain cellular entry by pharmaceutical drugs, and (ii) that a relatively simple but rapid clustering algorithm could produce clusters from which individual elements might serve to form a representative library covering natural products space. This exploited the fact that the larger clusters were likely to be formed early in evolution (and hence to have been accompanied by suitable transporters), so that very small clusters, including singletons, could be ignored. In the latter work, we assumed that the molecule chosen might be that in the middle of the cluster. However, this ignored two other criteria, namely the commercial availability and the financial cost of the individual elements of these clusters. We here develop a small representative library in which we to seek to satisfy the somewhat competing criteria of coverage ('representativeness'), availability and cost. It is intended that the library chosen might serve as a testbed of molecules that may or may not be substrates for known or orphan drug transporters. A supplementary spreadsheet provides details, and their availability via a particular supplier. PMID: 31485581 [PubMed]

Effects of Moxibustion and Moxa Smoke on Behavior Changes and Energy Metabolism in APP/PS1 Mice.

Fri, 06/09/2019 - 15:29
Related Articles Effects of Moxibustion and Moxa Smoke on Behavior Changes and Energy Metabolism in APP/PS1 Mice. Evid Based Complement Alternat Med. 2019;2019:9419567 Authors: Ha L, Yu M, Yan Z, Rui Z, Zhao B Abstract Objective: To investigate the antiaging effects of moxibustion and moxa smoke on APP/PS1 mice and to illustrate the mechanism of moxibustion improving Alzheimer's disease (AD). Methods: 36 male APP/PS1 mice were randomly assigned into three groups (n = 12), including a model control group, a moxibustion group, and a moxa smoke group. In addition, 12 C57BL/6 normal mice served as a normal (negative) control group. Mice in the moxibustion group received moxibustion intervention using Guanyuan (RN4) acupoint. Mice in the moxa smoke group received moxa smoke exposure with the same frequency as the moxibustion group. Behavioral tests were implemented in the 9th week, 3 days after the completion of the intervention. Tricarboxylic acid cycle and fatty acid metabolomics assessments of the mice were determined after behavioral tests. Results: In this study, relative to normal mice, we found that AD mice showed altered tricarboxylic and fatty acid metabolism and showed behavioral changes consistent with the onset of AD. However, both the moxibustion and moxa smoke interventions were able to mitigate these effects to some degree in AD mice. Conclusions: The data suggest that tricarboxylic acid cycle and unsaturated fatty acid metabolomics changes may be a target of AD, and the beneficial effects of moxibustion on cognitive behaviors may be mediated by the energy metabolism system. PMID: 31485251 [PubMed]

Corrigendum: Urine Organic Acids as Potential Biomarkers for Autism-Spectrum Disorder in Chinese Children.

Fri, 06/09/2019 - 15:29
Related Articles Corrigendum: Urine Organic Acids as Potential Biomarkers for Autism-Spectrum Disorder in Chinese Children. Front Cell Neurosci. 2019;13:388 Authors: Chen Q, Qiao Y, Xu XJ, You X, Tao Y Abstract [This corrects the article DOI: 10.3389/fncel.2019.00150.]. PMID: 31485210 [PubMed - in process]

Hyperoxia but not AOX expression mitigates pathological cardiac remodeling in a mouse model of inflammatory cardiomyopathy.

Fri, 06/09/2019 - 15:29
Related Articles Hyperoxia but not AOX expression mitigates pathological cardiac remodeling in a mouse model of inflammatory cardiomyopathy. Sci Rep. 2019 Sep 04;9(1):12741 Authors: Dhandapani PK, Begines-Moreno IM, Brea-Calvo G, Gärtner U, Graeber TG, Javier Sanchez G, Morty RE, Schönig K, Hoeve JT, Wietelmann A, Braun T, Jacobs HT, Szibor M Abstract Constitutive expression of the chemokine Mcp1 in mouse cardiomyocytes creates a model of inflammatory cardiomyopathy, with death from heart failure at age 7-8 months. A critical pathogenic role has previously been proposed for induced oxidative stress, involving NADPH oxidase activation. To test this idea, we exposed the mice to elevated oxygen levels. Against expectation, this prevented, rather than accelerated, the ultrastructural and functional signs of heart failure. This result suggests that the immune signaling initiated by Mcp1 leads instead to the inhibition of cellular oxygen usage, for which mitochondrial respiration is an obvious target. To address this hypothesis, we combined the Mcp1 model with xenotopic expression of the alternative oxidase (AOX), which provides a sink for electrons blocked from passage to oxygen via respiratory complexes III and IV. Ubiquitous AOX expression provided only a minor delay to cardiac functional deterioration and did not prevent the induction of markers of cardiac and metabolic remodeling considered a hallmark of the model. Moreover, cardiomyocyte-specific AOX expression resulted in exacerbation of Mcp1-induced heart failure, and failed to rescue a second cardiomyopathy model directly involving loss of cIV. Our findings imply that mitochondrial involvement in the pathology of inflammatory cardiomyopathy is multifaceted and complex. PMID: 31484989 [PubMed - in process]

In situ metabolomics of aldosterone-producing adenomas.

Fri, 06/09/2019 - 15:29
Related Articles In situ metabolomics of aldosterone-producing adenomas. JCI Insight. 2019 Sep 05;4(17): Authors: Murakami M, Rhayem Y, Kunzke T, Sun N, Feuchtinger A, Ludwig P, Strom TM, Gomez-Sanchez C, Knösel T, Kirchner T, Williams TA, Reincke M, Walch AK, Beuschlein F Abstract Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism. Matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI was conducted, and metabolite profiles were analyzed with genotype/phenotype information, including digital image analysis from morphometry and IHC of steroidogenic enzymes. Distinct molecular signatures between KCNJ5- and CACNA1D-mutated APAs with significant differences of 137 metabolites, including metabolites of purine metabolism and steroidogenesis, were observed. Intratumor concentration of 18-oxocortisol and 18-hydroxycortisol were inversely correlated with the staining intensity of CYP11B1. Lower staining intensity of CYP11B1 and higher levels of 18-oxocortisol were associated with a higher probability of complete clinical success after surgery. The present study demonstrates distinct metabolomic profiles of APAs in relation to tumor genotype. In addition, we reveal an inverse correlation between cortisol derivatives and CYP11B1 and the impact of 18-oxocortisol and CYP11B1 on clinical outcome, which provides unprecedented insights into the pathophysiology, clinical features, and steroidogenesis of APAs. PMID: 31484828 [PubMed - in process]

NMR-Based Metabolomics Profiling for Radical Scavenging and Anti-Aging Properties of Selected Herbs.

Fri, 06/09/2019 - 15:29
Related Articles NMR-Based Metabolomics Profiling for Radical Scavenging and Anti-Aging Properties of Selected Herbs. Molecules. 2019 Sep 03;24(17): Authors: Hussin M, Abdul Hamid A, Abas F, Ramli NS, Jaafar AH, Roowi S, Majid NA, Pak Dek MS Abstract Herbs that are usually recognized as medicinal plants are well known for their therapeutic effects and are traditionally used to treat numerous diseases, including aging. This study aimed to evaluate the metabolite variations among six selected herbs namely Curcurma longa, Oenanthe javanica, Vitex negundo, Pluchea indica, Cosmos caudatus and Persicaria minus using proton nuclear magnetic resonance (1H-NMR) coupled with multivariate data analysis (MVDA). The free radical scavenging activity of the extract was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assay. The anti-aging property was characterized by anti-elastase and anti-collagenase inhibitory activities. The results revealed that P. minus showed the highest radical scavenging activities and anti-aging properties. The partial least squares (PLS) biplot indicated the presence of potent metabolites in P. minus such as quercetin, quercetin-3-O-rhamnoside (quercitrin), myricetin derivatives, catechin, isorhamnetin, astragalin and apigenin. It can be concluded that P. minus can be considered as a potential source for an anti-aging ingredient and also a good free radical eradicator. Therefore, P. minus could be used in future development in anti-aging researches and medicinal ingredient preparations. PMID: 31484470 [PubMed - in process]

The Antialgal Mechanism of Luteolin-7-O-Glucuronide on Phaeocystis globosa by Metabolomics Analysis.

Fri, 06/09/2019 - 15:29
Related Articles The Antialgal Mechanism of Luteolin-7-O-Glucuronide on Phaeocystis globosa by Metabolomics Analysis. Int J Environ Res Public Health. 2019 Sep 03;16(17): Authors: Zhu J, Yang Y, Duan S, Sun D Abstract Antialgal compounds from plants have been identified as promising candidates for controlling harmful algal blooms (HABs). In our previous study, luteolin-7-O-glucuronide was used as a promising algistatic agent to control Phaeocystis globosa (P. globose) blooms; however, its antialgal mechanism on P. globosa have not yet been elaborated in detail. In this study, a liquid chromatography linked to tandem mass spectrometry (LC-MS/MS)-based untargeted metabolomic approach was used to investigate changes in intracellular and extracellular metabolites of P. globosa after exposure to luteolin-7-O-glucuronide. Significant differences in intracellular metabolites profiles were observed between treated and untreated groups; nevertheless, metabolic statuses for extracellular metabolites were similar among these two groups. For intracellular metabolites, 20 identified metabolites showed significant difference. The contents of luteolin, gallic acid, betaine and three fatty acids were increased, while the contents of α-Ketoglutarate and acetyl-CoA involved in tricarboxylic acid cycle, glutamate, and 11 organic acids were decreased. Changes in those metabolites may be induced by the antialgal compound in response to stress. The results revealed that luteolin played a vital role in the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, because luteolin increased the most in the treatment groups and had strong antialgal activity on P. globosa. α-Ketoglutarate and acetyl-CoA were the most inhibited metabolites, indicating that the antialgal compound inhibited the growth through disturbed the tricarboxylic acid (TCA) cycle of algal cells. To summarize, our data provides insights into the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, which can be used to further control P. globosa blooms. PMID: 31484378 [PubMed - in process]

metabolomics; +22 new citations

Thu, 05/09/2019 - 15:20
22 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 2019/09/05PubMed 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

Wed, 04/09/2019 - 15:12
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

Wed, 04/09/2019 - 12:12
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.

Tue, 03/09/2019 - 14:46
Related Articles 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.

Tue, 03/09/2019 - 14:46
Related Articles 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]

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