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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 15 min ago

An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats.

Sun, 08/09/2019 - 12:44
An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. J Pharm Biomed Anal. 2019 Aug 26;177:112837 Authors: Chen JQ, Chen YY, Tao HJ, Pu ZJ, Shi XQ, Zhang J, Tan YJ, Yue SJ, Zhou GS, Shang EX, Tang YP, Duan JA Abstract The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20-EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine. PMID: 31493746 [PubMed - as supplied by publisher]

Phytotoxicity induced by engineered nanomaterials as explored by metabolomics: Perspectives and challenges.

Sun, 08/09/2019 - 12:44
Phytotoxicity induced by engineered nanomaterials as explored by metabolomics: Perspectives and challenges. Ecotoxicol Environ Saf. 2019 Sep 04;184:109602 Authors: Li X, Peng T, Mu L, Hu X Abstract Given the wide applications of engineered nanomaterials (ENMs) in various fields, the ecotoxicology of ENMs has attracted much attention. The traditional plant physiological activity (e.g., reactive oxygen species and antioxidant enzymes) are limited in that they probe one specific process of nanotoxicity, which may result in the loss of understanding of other important biological reactions. Metabolites, which are downstream of gene and protein expression, are directly related to biological phenomena. Metabolomics is an easily performed and efficient tool for solving the aforementioned problems because it involves the comprehensive exploration of metabolic profiles. To understand the roles of metabolomics in phytotoxicity, the analytical methods for metabolomics should be organized and discussed. Moreover, the dominant metabolites and metabolic pathways are similar in different plants, which determines the universal applicability of metabolomics analysis. The analysis of regulated metabolism will globally and scientifically help determine the ecotoxicology that is induced by ENMs. In the past several years, great developments in nanotoxicology have been achieved using metabolomics. However, many knowledge gaps remain, such as the relationships between biological responses that are induced by ENMs and the regulation of metabolism (e.g., carbohydrate, energy, amino acid, lipid and secondary metabolism). The phytotoxicity that is induced by ENMs has been explored by metabolomics, which is still in its infancy. The detrimental and defence mechanisms of plants in their response to ENMs at the level of metabolomics also deserve much attention. In addition, owing to the regulation of metabolism in plants by ENMs affected by multiple factors, it is meaningful to uniformly identify the key influencing factor. PMID: 31493589 [PubMed - as supplied by publisher]

Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation, Applications, and the Road Ahead.

Sun, 08/09/2019 - 12:44
Related Articles Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation, Applications, and the Road Ahead. J Am Soc Mass Spectrom. 2019 Sep 06;: Authors: Dodds JN, Baker ES Abstract Ion mobility spectrometry (IMS) is a rapid separation technique that has experienced exponential growth as a field of study. Interfacing IMS with mass spectrometry (IMS-MS) provides additional analytical power as complementary separations from each technique enable multidimensional characterization of detected analytes. IMS separations occur on a millisecond timescale, and therefore can be readily nested into traditional GC and LC/MS workflows. However, the continual development of novel IMS methods has generated some level of confusion regarding the advantages and disadvantages of each. In this critical insight, we aim to clarify some common misconceptions for new users in the community pertaining to the fundamental concepts of the various IMS instrumental platforms (i.e., DTIMS, TWIMS, TIMS, FAIMS, and DMA), while addressing the strengths and shortcomings associated with each. Common IMS-MS applications are also discussed in this review, such as separating isomeric species, performing signal filtering for MS, and incorporating collision cross-section (CCS) values into both targeted and untargeted omics-based workflows as additional ion descriptors for chemical annotation. Although many challenges must be addressed by the IMS community before mobility information is collected in a routine fashion, the future is bright with possibilities. PMID: 31493234 [PubMed - as supplied by publisher]

Role of purines in regulation of metabolic reprogramming.

Sun, 08/09/2019 - 12:44
Related Articles Role of purines in regulation of metabolic reprogramming. Purinergic Signal. 2019 Sep 06;: Authors: Tang Z, Ye W, Chen H, Kuang X, Guo J, Xiang M, Peng C, Chen X, Liu H Abstract Purines, among most influential molecules, are reported to have essential biological function by regulating various cell types. A large number of studies have led to the discovery of many biological functions of the purine nucleotides such as ATP, ADP, and adenosine, as signaling molecules that engage G protein-coupled or ligand-gated ion channel receptors. The role of purines in the regulation of cellular functions at the gene or protein level has been well documented. With the advances in multiomics, including those from metabolomic and bioinformatic analyses, metabolic reprogramming was identified as a key mechanism involved in the regulation of cellular function under physiological or pathological conditions. Recent studies suggest that purines or purine-derived products contribute to important regulatory functions in many fundamental biological and pathological processes related to metabolic reprogramming. Therefore, this review summarizes the role and potential mechanism of purines in the regulation of metabolic reprogramming. In particular, the molecular mechanisms of extracellular purine- and intracellular purine-mediated metabolic regulation in various cells during disease development are discussed. In summary, our review provides an extensive resource for studying the regulatory role of purines in metabolic reprogramming and sheds light on the utilization of the corresponding peptides or proteins for disease diagnosis and therapy. PMID: 31493132 [PubMed - as supplied by publisher]

Genome-wide association studies of 74 plasma metabolites of German shepherd dogs reveal two metabolites associated with genes encoding their enzymes.

Sun, 08/09/2019 - 12:44
Related Articles Genome-wide association studies of 74 plasma metabolites of German shepherd dogs reveal two metabolites associated with genes encoding their enzymes. Metabolomics. 2019 Sep 06;15(9):123 Authors: Soh PXY, Marin Cely JM, Mortlock SA, Jara CJ, Booth R, Natera S, Roessner U, Crossett B, Cordwell S, Singh Khatkar M, Williamson P Abstract INTRODUCTION: German shepherd dogs (GSDs) are a popular breed affected by numerous disorders. Few studies have explored genetic variations that influence canine blood metabolite levels. OBJECTIVES: To investigate genetic variants affecting the natural metabolite variation in GSDs. METHODS: A total of 82 healthy GSDs were genotyped on the Illumina CanineHD Beadchip, assaying 173,650 markers. For each dog, 74 metabolites were measured through liquid and gas chromatography mass spectrometry (LC-MS and GC-MS) and were used as phenotypes for genome-wide association analyses (GWAS). Sliding window and homozygosity analyses were conducted to fine-map regions of interest, and to identify haplotypes and gene dosage effects. RESULTS: Summary statistics for 74 metabolites in this population of GSDs are reported. Forty-one metabolites had significant associations at a false discovery rate of 0.05. Two associations were located around genes which encode for enzymes for the relevant metabolites: 4-hydroxyproline was significantly associated to D-amino acid oxidase (DAO), and threonine to L-threonine 3-dehydrogenase (LOC477365). Three of the top ten haplotypes associated to 4-hydroxyproline included at least one SNP on DAO. These haplotypes occurred only in dogs with the highest 15 measurements of 4-hydroxyproline, ranging in frequency from 16.67 to 20%. None of the dogs were homozygous for these haplotypes. The top two haplotypes associated to threonine included SNPs on LOC477365 and were also overrepresented in dogs with the highest 15 measurements of threonine. These haplotypes occurred at a frequency of 90%, with 80% of these dogs homozygous for the haplotypes. In dogs with the lowest 15 measurements of threonine, the haplotypes occurred at a frequency of 26.67% and 0% homozygosity. CONCLUSION: DAO and LOC477365 were identified as candidate genes affecting the natural plasma concentration of 4-hydroxyproline and threonine, respectively. Further investigations are needed to validate the effects of the variants on these genes. PMID: 31493001 [PubMed - in process]

Serotonin is elevated in risk-genotype carriers of TCF7L2 - rs7903146.

Sun, 08/09/2019 - 12:44
Related Articles Serotonin is elevated in risk-genotype carriers of TCF7L2 - rs7903146. Sci Rep. 2019 Sep 06;9(1):12863 Authors: Leiherer A, Muendlein A, Saely CH, Fraunberger P, Drexel H Abstract The transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146 is known to be tightly associated with an elevated risk for type 2 diabetes, whereas the molecular mechanisms remain elusive. We evaluated the metabolic profile of a total of 394 patients' serum samples with respect to their rs7903146 genotype using targeted metabolomics in a discovery (n = 154) and a validation (n = 240) study. We have identified serotonin as the top metabolite being increased in carriers of the risk allele. Serotonin was significantly associated with the rs7903146 genotype after full adjustment including type 2 diabetes and further top ranked metabolites. Given the role of peripheral serotonin in metabolic homeostasis and type 2 diabetes, this finding provides a first hint that the well-known impact of the TCF7L2 polymorphism on type 2 diabetes risk may involve a serotonin-dependent pathway. PMID: 31492908 [PubMed - in process]

Prognostic Relevance of Steroid Sulfation in Adrenocortical Carcinoma Revealed by Molecular Phenotyping Using High-Resolution Mass Spectrometry Imaging.

Sun, 08/09/2019 - 12:44
Related Articles Prognostic Relevance of Steroid Sulfation in Adrenocortical Carcinoma Revealed by Molecular Phenotyping Using High-Resolution Mass Spectrometry Imaging. Clin Chem. 2019 Sep 06;: Authors: Sun N, Kunzke T, Sbiera S, Kircher S, Feuchtinger A, Aichler M, Herterich S, Ronchi CL, Weigand I, Schlegel N, Waldmann J, Fragoso MCV, Whitsett TG, Gill AJ, Fassnacht M, Walch A, Kroiss M Abstract BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor with variable prognosis even within the same tumor stage. Cancer-related sex hormones and their sulfated metabolites in body fluids can be used as tumor markers. The role of steroid sulfation in ACC has not yet been studied. MALDI mass spectrometry imaging (MALDI-MSI) is a novel tool for tissue-based chemical phenotyping. METHODS: We performed phenotyping of formalin-fixed, paraffin-embedded tissue samples from 72 ACC by MALDI-MSI at a metabolomics level. RESULTS: Tumoral steroid hormone metabolites- estradiol sulfate [hazard ratio (HR) 0.26; 95% CI, 0.10-0.69; P = 0.005] and estrone 3-sulfate (HR 0.22; 95% CI, 0.07-0.63; P = 0.003)-were significantly associated with prognosis in Kaplan-Meier analyses and after multivariable adjustment for age, tumor stage, and sex (HR 0.29; 95% CI, 0.11-0.79; P = 0.015 and HR 0.30; 95% CI, 0.10-0.91; P = 0.033, respectively). Expression of sulfotransferase SULT2A1 was associated with prognosis to a similar extent and was validated to be a prognostic factor in two published data sets. We discovered the presence of estradiol-17β 3,17-disulfate (E2S2) in a subset of tumors with particularly poor overall survival. Electron microscopy revealed novel membrane-delimited organelles in only these tumors. By applying cluster analyses of metabolomic data, 3 sulfation-related phenotypes exhibited specific metabolic features unrelated to steroid metabolism. CONCLUSIONS: MALDI-MSI provides novel insights into the pathophysiology of ACC. Steroid hormone sulfation may be used for prognostication and treatment stratification. Sulfation-related metabolic reprogramming may be of relevance also in conditions beyond the rare ACC and can be directly investigated by the use of MALDI-MSI. PMID: 31492715 [PubMed - as supplied by publisher]

PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1.

Sun, 08/09/2019 - 12:44
Related Articles PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1. Mol Cell. 2019 Aug 22;: Authors: Qian X, Li X, Shi Z, Xia Y, Cai Q, Xu D, Tan L, Du L, Zheng Y, Zhao D, Zhang C, Lorenzi PL, You Y, Jiang BH, Jiang T, Li H, Lu Z Abstract The PTEN tumor suppressor is frequently mutated or deleted in cancer and regulates glucose metabolism through the PI3K-AKT pathway. However, whether PTEN directly regulates glycolysis in tumor cells is unclear. We demonstrate here that PTEN directly interacts with phosphoglycerate kinase 1 (PGK1). PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation. The protein phosphatase activity of PTEN dephosphorylates and inhibits autophosphorylated PGK1, thereby inhibiting glycolysis, ATP production, and brain tumor cell proliferation. In addition, knockin expression of a PGK1 Y324F mutant inhibits brain tumor formation. Analyses of human glioblastoma specimens reveals that PGK1 Y324 phosphorylation levels inversely correlate with PTEN expression status and are positively associated with poor prognosis in glioblastoma patients. This work highlights the instrumental role of PGK1 autophosphorylation in its activation and PTEN protein phosphatase activity in governing glycolysis and tumorigenesis. PMID: 31492635 [PubMed - as supplied by publisher]

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]

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