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

metabolomics; +25 new citations

Tue, 28/04/2020 - 15:35
25 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 2020/04/28PubMed 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; +25 new citations

Tue, 28/04/2020 - 12:35
25 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 2020/04/28PubMed 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.

Time Course of Changes in Sorafenib-Treated Hepatocellular Carcinoma (HCC) Cells Suggests Involvement of Phospho-Regulated Signaling in Ferroptosis Induction.

Mon, 27/04/2020 - 15:27
Related Articles Time Course of Changes in Sorafenib-Treated Hepatocellular Carcinoma (HCC) Cells Suggests Involvement of Phospho-Regulated Signaling in Ferroptosis Induction. Proteomics. 2020 Apr 26;:e2000006 Authors: Werth EG, Rajbhandari P, Stockwell BR, Brown LM Abstract Ferroptosis is a form of regulated, non-apoptotic cell death characterized by excessive lipid peroxidation that can be triggered by inhibition of the cystine-glutamate antiporter, system Xc - . Sorafenib, an FDA-approved multi-kinase inhibitor drug that is used for treatment of hepatocellular carcinoma (HCC), has been shown to induce ferroptosis. Protein phosphorylation changes upon sorafenib treatment have been previously reported in patient studies and in cell culture. However, early phosphorylation changes during induction of ferroptosis are not reported. This work highlights these changes through a time course from 7 to 60 min of sorafenib treatment in human (SKHep1) HCC cells. A total of 6,170 unique phosphosites from 2,381 phosphoproteins were quantified, and phosphorylation changes occurred after as little as 30 minutes of sorafenib treatment. By 60 minutes, notable changes included phosphosites significantly changing on p53 (P04637), CAD protein (P27708), and proteins important for iron homeostasis, such as FTH1 (P02794), HMOX1 (P09601), and PCBP1 (Q15365). Additional sites on proteins in key regulatory pathways were identified, including sites in ferroptosis-related proteins, indicating the likely involvement of phospho-regulated signaling during ferroptosis induction. This article is protected by copyright. All rights reserved. PMID: 32336023 [PubMed - as supplied by publisher]

In memory of Michael J. O. Wakelam (1955-2020): a pioneer in lipid signalling and lipidomics.

Mon, 27/04/2020 - 15:27
Related Articles In memory of Michael J. O. Wakelam (1955-2020): a pioneer in lipid signalling and lipidomics. Metabolomics. 2020 Apr 25;16(5):60 Authors: Griffin JL PMID: 32335753 [PubMed - as supplied by publisher]

Metabolomics and hormonomics to crack the code of filbert growth.

Mon, 27/04/2020 - 15:27
Related Articles Metabolomics and hormonomics to crack the code of filbert growth. Metabolomics. 2020 Apr 25;16(5):62 Authors: Erland LAE, Turi CE, Saxena PK, Murch SJ Abstract INTRODUCTION: Plants respond to changes in their environments through hormonal activation of a physiological cascade that redirects metabolic resources and growth. In filberts (Corylus sp.), chelated iron promotes the growth of new shoots but the mechanism(s) are not understood. OBJECTIVES: To use untargeted metabolomics and hormonomics approaches to generate novel hypotheses for the morphoregulatory role of ferric ethylenediamine-N,N'-di-(ortho-hydroxyphenyl) acetic acid (Fe-EDDHA) in filbert shoot organogenesis in vitro. METHODS: Data were generated using previously optimized standardized untargeted metabolomics protocols with time of flight mass spectrometry. Multivariate statistical tools (principal component and partial least squares discriminant analysis) did not detect significant differences. Discovery tools Significance Analysis of Microarrays (SAM), multiple linear regression analysis, Bayesian analysis, logical algorithms, machine learning, synthetic biotransformations, targeted hormonomics, and online resources including MetaboAnalyst were used. RESULTS: Starch/sucrose metabolism and shikimate pathway metabolites were increased. Dose dependent decreases were found in polyphenol metabolism, specifically ellagic acid and its methylated derivative 3,4,3'-tri-O-methylellagic acid. Hormonomics analysis revealed significant differences in phytohormones and their conjugates. FeEDDHA treatment reduced indole-3-acetic acid, abscisic acid, salicylic acid, jasmonic acid conjugates (JA-Trp, JA-Ile, OH-JA) and dihydrozeatinglucoside in regenerating explants. Serotonin (5HT) was decreased in FeEDDHA-treated regenerating tissues while the related metabolite melatonin was increased. Eight phenolic conjugates of 5HT and eight catabolites were affected by FeEDDHA indicating that metabolism to sequester, deactivate and metabolize 5HT was induced by Fe(III). Tryptophan was metabolized through kynurenine but not anthranilate. CONCLUSION: Seven novel hypotheses were generated to guide future studies to understand the regulatory control(s) of shoot organogenesis. PMID: 32335734 [PubMed - as supplied by publisher]

Differential correlation network analysis identified novel metabolomics signatures for non-responders to total joint replacement in primary osteoarthritis patients.

Mon, 27/04/2020 - 15:27
Related Articles Differential correlation network analysis identified novel metabolomics signatures for non-responders to total joint replacement in primary osteoarthritis patients. Metabolomics. 2020 Apr 25;16(5):61 Authors: Costello CA, Hu T, Liu M, Zhang W, Furey A, Fan Z, Rahman P, Randell EW, Zhai G Abstract INTRODUCTION: Up to one third of total joint replacement patients (TJR) experience poor surgical outcome. OBJECTIVES: To identify metabolomic signatures for non-responders to TJR in primary osteoarthritis (OA) patients. METHODS: A newly developed differential correlation network analysis method was applied to our previously published metabolomic dataset to identify metabolomic network signatures for non-responders to TJR. RESULTS: Differential correlation networks involving 12 metabolites and 23 metabolites were identified for pain non-responders and function non-responders, respectively. CONCLUSION: The differential networks suggest that inflammation, muscle breakdown, wound healing, and metabolic syndrome may all play roles in TJR response, warranting further investigation. PMID: 32335722 [PubMed - as supplied by publisher]

Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry.

Mon, 27/04/2020 - 15:27
Related Articles Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry. Metabolomics. 2020 Apr 25;16(5):63 Authors: Ohbuchi K, Sakurai N, Kitagawa H, Sato M, Suzuki H, Kushida H, Nishi A, Yamamoto M, Hanazaki K, Arita M Abstract INTRODUCTION: Traditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential. OBJECTIVE: The aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans. METHODS: We performed untargeted metabolome analysis of human plasma collected before and after administration of maoto (ma-huang-tang), a traditional Japanese Kampo medicine. Maoto-derived metabolites were then selected and annotated following the DAC-Met strategy, which is an annotation method that uses mass differences of major metabolic reactions among the detected peaks and a differential network analysis. RESULTS: About 80% of maoto-derived components were found to be converted forms. Following DAC-Met, the structures of 15 previously unidentified metabolites were determined, and five of these were later confirmed with authentic standards. Using published literature, we also reconstructed the metabolic pathway of maoto components in humans. A kinetic time-course analysis revealed their diverse kinetic profiles. CONCLUSION: The results demonstrated that time-resolved comprehensive metabolite profiling in plasma using the DAC-Met strategy is highly useful for elucidating the complex nature of THM. PMID: 32335721 [PubMed - as supplied by publisher]

Different Signatures of High Cardiorespiratory Capacity Revealed With Metabolomic Profiling in Elite Athletes.

Mon, 27/04/2020 - 15:27
Related Articles Different Signatures of High Cardiorespiratory Capacity Revealed With Metabolomic Profiling in Elite Athletes. Int J Sports Physiol Perform. 2020 Apr 25;:1-12 Authors: Monnerat G, Sánchez CAR, Santos CGM, Paulucio D, Velasque R, Evaristo GPC, Evaristo JAM, Nogueira FCS, Domont GB, Serrato M, Lima AS, Bishop D, Campos de Carvalho AC, Pompeu FAMS Abstract PURPOSE: High cardiorespiratory capacity is a key determinant of human performance and life expectancy; however, the underlying mechanisms are not fully understood. The objective of this pilot study was to investigate biochemical signatures of endurance-performance athletes using high-resolution nontargeted metabolomics. METHODS: Elite long-distance runners with similar training and anthropometrical records were studied. After athletes' maximal oxygen consumption (V˙O2max) was measured, they were divided into 2 groups: low V˙O2max (<65 mL·kg-1·min-1, n = 7) and high V˙O2max (>75 mL·kg-1·min-1, n = 7). Plasma was collected under basal conditions after 12 hours of fasting and after a maximal exercise test (nonfasted) and analyzed by high-resolution LC-MS. Multivariate and univariate statistics were applied. RESULTS: A total of 167 compounds were putatively identified with an LC-MS-based metabolomics pipeline. Partial least-squares discriminant analysis showed a clear separation between groups. Significant variations in metabolites highlighted group differences in diverse metabolic pathways, including lipids, vitamins, amino acids, purine, histidine, xenobiotics, and others, either under basal condition or after the maximal exercise test. CONCLUSIONS: Taken together, the metabolic alterations revealed in the study affect cellular energy use and availability, oxidative stress management, muscle damage, central nervous system signaling metabolites, nutrients, and compound bioavailability, providing new insights into metabolic alterations associated with exercise and cardiorespiratory fitness levels in trained athletes. PMID: 32335533 [PubMed - as supplied by publisher]

Evaluation of multi-starter S. cerevisiae/ D. bruxellensis cultures for mimicking and accelerating transformations occurring during barrel ageing of beer.

Mon, 27/04/2020 - 15:27
Related Articles Evaluation of multi-starter S. cerevisiae/ D. bruxellensis cultures for mimicking and accelerating transformations occurring during barrel ageing of beer. Food Chem. 2020 Apr 15;323:126826 Authors: Coelho E, Azevedo M, Teixeira JA, Tavares T, Oliveira JM, Domingues L Abstract During beer ageing, endogenous barrel microbes grow spontaneously and transform wort/beer composition, being Dekkera bruxellensis and Saccharomyces cerevisiae among the main contributors to the chemical and sensory profile of aged beer. This work aims at the application of multi-starter cultures to mimic and accelerate biological modifications occurring during barrel ageing of beer, in controlled fermentation processes. Co-cultures of D.bruxellensis/S.cerevisiae were conducted under conditions commonly found in barrel aged beer production: different pitching rates, high glucose concentration and presence of ethanol and wood extracts. Selective pressures and competition between yeasts influenced microbial growth and metabolite production, namely ethanol, acetic acid and target volatile compounds (esters, alcohols, terpenols, volatile acids and volatile phenols). Metabolic profiles of co-cultures combined traits of both species, and differed from those of pure cultures. Lastly, multi-starters were successfully applied in combination with wood in a controlled and accelerated fermentation process for mimicking barrel ageing transformations. PMID: 32335460 [PubMed - as supplied by publisher]

Assessment of substrate biodegradability improvement in anaerobic Co-digestion using a chemometrics-based metabolomic approach.

Mon, 27/04/2020 - 15:27
Related Articles Assessment of substrate biodegradability improvement in anaerobic Co-digestion using a chemometrics-based metabolomic approach. Chemosphere. 2020 Apr 17;254:126812 Authors: Puig-Castellví F, Cardona L, Jouan-Rimbaud Bouveresse D, Cordella CBY, Mazéas L, Rutledge DN, Chapleur O Abstract Anaerobic co-digestion (AcoD) can increase methane production of anaerobic digesters in plants treating wastewater sludge by improving the nutrient balance needed for the microorganisms to grow in the digesters, resulting in a faster process stabilization. Substrate mixture proportions are usually optimized in terms of biogas production, while the metabolic biodegradability of the whole mixture is neglected in this optimisation. In this aim, we developed a strategy to assess AcoD using metabolomics data. This strategy was explored in two different systems. Specifically, we investigated the co-digestion of wastewater sludge with different proportions of either grass or fish waste using untargeted High Performance Liquid Chromatography coupled to Mass Spectrometry (HPLC-MS) metabolomics and chemometrics methods. The analysis of these data revealed that adding grass waste did not improve the metabolic biodegradability of wastewater sludge. Conversely, a synergistic effect in the metabolic biodegradability was observed when fish waste was used, this effect being the highest for 25% of fish waste. In conclusion, metabolomics can be regarded as a promising tool both for characterizing the biochemical processes occurring during anaerobic digestion, and for providing a better understanding of the anaerobic digestion processes. PMID: 32335442 [PubMed - as supplied by publisher]

How the cells were injured and the secondary metabolites in the shikimate pathway were changed by boron deficiency in trifoliate orange root.

Mon, 27/04/2020 - 15:27
Related Articles How the cells were injured and the secondary metabolites in the shikimate pathway were changed by boron deficiency in trifoliate orange root. Plant Physiol Biochem. 2020 Apr 10;151:630-639 Authors: Wu X, Riaz M, Yan L, Zhang Z, Jiang C Abstract Boron (B) deficiency is frequently observed in citrus orchards as a major cause for loss of productivity and quality. The structural and morphological responses of roots to B deficiency have been reported in some plants. The study was conducted to get novel information about the B-deficient-induced cellular injuries and target secondary metabolites in the shikimate pathway. Fluorescent vital staining, paraffin section, transmission electron microscopy (TEM) and target metabolomics were to investigate the responses of the cell viability and structure, and target aromatic metabolites in the shikimate pathway in B-deficient trifoliate orange roots. Boron deprivation-induced ROS accumulation accelerated the membrane peroxidation, resulting in weakened cell vitality and cell rupture in roots. In addition, B deficiency increased phenylalanine (Phe), tyrosine (Try) in roots, thereby promoting the biosynthesis of salicylic acid, caffeic acid and ferulic acid. B-starvation up-regulated salicylic acid and lignin while reduced 3-indoleacetic acid (IAA) content. These adverse effects might be involved in the structural and morphological changes in B-deficient roots. What is more, the results provide a new insight into the mechanism of B deficiency-induced structural damage and elongation inhibition on roots. PMID: 32335386 [PubMed - as supplied by publisher]

Urinary proteome and metabolome in dogs (Canis lupus familiaris): The effect of chronic kidney disease.

Mon, 27/04/2020 - 15:27
Related Articles Urinary proteome and metabolome in dogs (Canis lupus familiaris): The effect of chronic kidney disease. J Proteomics. 2020 Apr 23;:103795 Authors: Ferlizza E, Isani G, Dondi F, Andreani G, Vasylyeva K, Bellei E, Almeida AM, Matzapetakis M Abstract Chronic kidney disease (CKD) is a progressive and irreversible disease. Although urine is an ideal biological sample for proteomics and metabolomics studies, sensitive and specific biomarkers are currently lacking in dogs. This study characterised dog urine proteome and metabolome aiming to identify and possibly quantify putative biomarkers of CKD in dogs. Twenty-two healthy dogs and 28 dogs with spontaneous CKD were selected and urine samples were collected. Urinary proteome was separated by SDS-PAGE and analysed by mass spectrometry, while urinary metabolome was analysed in protein-depleted samples by 1D 1H NMR spectra. The most abundant proteins in urine samples from healthy dogs were uromodulin, albumin and, in entire male dogs, arginine esterase. In urine samples from CKD dogs, the concentrations of uromodulin and albumin were significantly lower and higher, respectively, than in healthy dogs. In addition, these samples were characterised by a more complex protein pattern indicating mixed glomerular (protein bands ≥65 kDa) and tubular (protein bands<65 kDa) proteinuria. Urine spectra acquired by NMR allowed the identification of 86 metabolites in healthy dogs, belonging to 49 different pathways mainly involved in amino acid metabolism, purine and aminoacyl-tRNA biosynthesis or tricarboxylic acid cycle. Seventeen metabolites showed significantly different concentrations when comparing healthy and CKD dogs. In particular, carnosine, trigonelline, and cis-aconitate, might be suggested as putative biomarkers of CKD in dogs. SIGNIFICANCE: Urine is an ideal biological sample, however few proteomics and metabolomics studies investigated this fluid in dogs and in the context of CKD (chronic kidney disease). In this research, applying a multi-omics approach, new insights were gained regarding the molecular changes triggered by this disease in canine urinary proteome and metabolome. In particular, the involvement of the tubular component was highlighted, suggesting uromodulin, trigonelline and carnosine as possible biomarkers of CKD in dogs. PMID: 32335294 [PubMed - as supplied by publisher]

The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?

Mon, 27/04/2020 - 15:27
Related Articles The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota? Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 23;:109951 Authors: Misiak B, Łoniewski I, Marlicz W, Frydecka D, Szulc A, Rudzki L, Samochowiec J Abstract Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders. PMID: 32335265 [PubMed - as supplied by publisher]

Phenylalanine stable isotope tracer labeling of cow milk and meat and human experimental applications to study dietary protein-derived amino acid availability.

Mon, 27/04/2020 - 15:27
Related Articles Phenylalanine stable isotope tracer labeling of cow milk and meat and human experimental applications to study dietary protein-derived amino acid availability. Clin Nutr. 2020 Mar 26;: Authors: Reitelseder S, Tranberg B, Agergaard J, Dideriksen K, Højfeldt G, Merry ME, Storm AC, Poulsen KR, Hansen ET, van Hall G, Lund P, Holm L Abstract BACKGROUND & AIMS: Availability of dietary protein-derived amino acids (AA) is an important determinant for their utilization in metabolism and for protein synthesis. Intrinsic labeling of protein is the only method to directly trace availability and utilization. The purpose of the present study was to produce labeled milk and meat proteins and investigate how dietary protein-derived AA availability is affected by the protein-meal matrix. METHODS: Four lactating cows were infused with L-[ring-d5]phenylalanine and one with L-[15N]phenylalanine for 72 h. Milk was collected, and three of the [d5]phenylalanine cows were subsequently slaughtered. Two human studies were performed to explore plasma AA availability properties utilizing the labeled proteins. One study compared the intake of whey protein either alone or together with carbohydrates-fat food-matrix. The other study compared the intake of meat hydrolysate with minced beef. Cow blood, milk, meat and human blood samples were collected and analyzed by mass spectrometry. RESULTS: Whey and caseinate acquired label to 15-20 mol percent excess (MPE), and the meat proteins reached 0.41-0.73 MPE. The [d5]phenylalanine appeared fast in plasma and peaked 30 min after whey protein alone and meat hydrolysate intake, whereas whey protein with a food-matrix and the meat minced beef postponed the [d5]phenylalanine peak until 2 and 1 h, respectively. CONCLUSIONS: Phenylalanine stable isotope-labeled milk and meat were produced and proved a valuable tool to investigate AA absorption characteristics. Dietary protein in food-matrices showed delayed postprandial plasma AA availability as compared to whey protein alone and meat hydrolysate. PMID: 32334880 [PubMed - as supplied by publisher]

Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice.

Mon, 27/04/2020 - 15:27
Related Articles Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice. Microb Cell Fact. 2020 Apr 25;19(1):94 Authors: Bai L, Gao M, Cheng X, Kang G, Cao X, Huang H Abstract BACKGROUND: Obesity is a major problem worldwide and severely affects public safety. As a metabolite of gut microbiota, endogenous butyric acid participates in energy and material metabolism. Considering the serious side effects and weight regain associated with existing weight loss interventions, novel strategies are urgently needed for prevention and treatment of obesity. RESULTS: In the present study, we engineered Bacillus subtilis SCK6 to exhibited enhanced butyric acid production. Compared to the original Bacillus subtilis SCK6 strain, the genetically modified BsS-RS06550 strain had higher butyric acid production. The mice were randomly divided into four groups: a normal diet (C) group, a high-fat diet (HFD) group, an HFD + Bacillus subtilis SCK6 (HS) group and an HFD + BsS-RS06550 (HE) group. The results showed BsS-RS06550 decreased the body weight, body weight gain, and food intake of HFD mice. BsS-RS06550 had beneficial effects on blood glucose, insulin resistance and hepatic biochemistry. After the 14-week of experiment, fecal samples were collected for nontargeted liquid chromatography-mass spectrometry analysis to identify and quantify significant changes in metabolites. Sixteen potentially significant metabolites were screened, and BsS-RS06550 was shown to potentially regulate disorders in glutathione, methionine, tyrosine, phenylalanine, and purine metabolism and secondary bile acid biosynthesis. CONCLUSIONS: In this study, we successfully engineered Bacillus subtilis SCK6 to have enhanced butyric acid production. The results of this work revealed that the genetically modified live bacterium BsS-RS06550 showed potential anti-obesity effects, which may have been related to regulating the levels of metabolites associated with obesity. These results indicate that the use of BsS-RS06550 may be a promising strategy to attenuate obesity. PMID: 32334588 [PubMed - as supplied by publisher]

Identification of key taste components in loquat using widely targeted metabolomics.

Sun, 26/04/2020 - 12:19
Identification of key taste components in loquat using widely targeted metabolomics. Food Chem. 2020 Apr 18;323:126822 Authors: Zou S, Wu J, Shahid MQ, He Y, Lin S, Liu Z, Yang X Abstract Loquats can be divided into white- and yellow-fleshed cultivars. Generally, white-fleshed cultivars taste better than yellow-fleshed cultivars. Currently, metabolic causes of differences in taste are unknown, due to the lack of a large-scale and comprehensive investigation of metabolites in loquat fruit. Here, we performed a LC-MS/MS-based widely targeted metabolome analysis on two cultivars, 'Baiyu' (white-fleshed) and 'ZaozhongNo. 6' (yellow-fleshed). A total of 536 metabolites were identified, 193 of which (including 7 carbohydrates, 12 organic acids and 8 amino acids) were different between the cultivars. Pathway enrichment analysis also identified significant differences in phenolic pathways between the cultivars. Our results suggest that taste differences between the cultivars can be explained by variations in composition and abundance of carbohydrates, organic acids, amino acids, and phenolics. This study provides new insights into the underlying metabolic causes of taste variation in loquat. PMID: 32334307 [PubMed - as supplied by publisher]

Network pharmacology and metabolomics study on the intervention of traditional Chinese medicine Huanglian Decoction in rats with type 2 diabetes mellitus.

Sun, 26/04/2020 - 12:19
Network pharmacology and metabolomics study on the intervention of traditional Chinese medicine Huanglian Decoction in rats with type 2 diabetes mellitus. J Ethnopharmacol. 2020 Apr 22;:112842 Authors: Pan L, Li Z, Wang Y, Zhang B, Liu G, Liu J Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Type 2 diabetes mellitus (T2DM) is currently one of the most prominent and global chronic conditions. Huanglian Decoction (HLD) is a traditional Chinese medicine (TCM) preparation that has been used to treat T2DM for thousands of years in China. However, its mechanism of action at the metabolic level is still unclear. AIM OF THE STUDY: The purpose of this work is to study the mechanism of HLD in treating T2DM based on metabolomics and network pharmacology. MATERIALS AND METHODS: In this study, metabolomics combined with network pharmacology was used to elucidate the therapeutic mechanism of HLD in T2DM. Serum samples were collected from rats with T2DM, induced by a high-sugar and high-fat diet combined with streptozotocin (STZ), to measure the levels of biochemical markers. Urinary metabolomics-based analysis using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) was conducted to evaluate the differential metabolites from multiple metabolic pathways. RESULTS: After treatment with HLD for 4 weeks, biochemical indicators, including fasting blood glucose (FBG), blood lipid, fasting insulin (FINS), insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR), were significantly improved. Metabolomics results revealed that HLD regulated the biomarkers, such as cytosine, L-carnitine, betaine, phenylalanine, glucose, citrate, phenylpyruvate, and hippuric acid in glyoxylate and dicarboxylate metabolism, phenylalanine metabolism, and tricarboxylic acid (TCA) cycle. The combination of network pharmacology, metabolomics, western blot, and PCR showed that HLD can treat T2DM by enhancing the gene and protein expression levels of glucose transporter 4 (GLUT4), insulin receptor (INSR), and mitogen-activated protein kinase 1 (MAPK1) to interfere with glyoxylate and dicarboxylate metabolism. CONCLUSIONS: The study based on metabolomics and network pharmacology indicated that HLD can improve T2DM through multiple targets and pathways, and it may be a useful alternative therapy for the treatment of T2DM. PMID: 32333952 [PubMed - as supplied by publisher]

Heat stress response in the closest algal relatives of land plants reveals conserved stress signaling circuits.

Sun, 26/04/2020 - 12:19
Related Articles Heat stress response in the closest algal relatives of land plants reveals conserved stress signaling circuits. Plant J. 2020 Apr 24;: Authors: de Vries J, de Vries S, Curtis BA, Zhou H, Penny S, Feussner K, Pinto DM, Steinert M, Cohen A, von Schwartzenberg K, Archibald JM Abstract All land plants (embryophytes) share a common ancestor that likely evolved from a filamentous freshwater alga. Elucidating the transition from algae to embryophytes-and the eventual conquering of Earth's surface-is one of the most fundamental questions in plant evolutionary biology. Here, we investigated one of the organismal properties that might have enabled this transition: resistance to drastic temperature shifts. We explored the effect of heat stress in Mougeotia and Spirogyra, two representatives of Zygnematophyceae-the closest known algal sister lineage to land plants. Heat stress induced pronounced phenotypic alterations of their plastids, and HPLC-MS/MS-based profiling of 565 transitions for the analysis of main central metabolites revealed significant shifts in 43 compounds. We also analyzed the global differential gene expression responses triggered by heat, generating 92.8 Gbp of sequence data and assembling a combined set of 8,905 well-expressed genes. Each organism had its own distinct gene expression profile; less than half of their shared genes showed concordant gene expression trends. We nevertheless detected common signature responses to heat such as elevated transcript levels for molecular chaperones, thylakoid components, and-corroborating our metabolomic data-amino acid metabolism. We also uncovered the heat-stress responsiveness of genes for phosphorelay-based signal transduction that link environmental cues, calcium signatures and plastid biology. Our data allow us to infer the molecular heat stress response that the earliest land plants might have used when facing the rapidly shifting temperature conditions of the terrestrial habitat. PMID: 32333477 [PubMed - as supplied by publisher]

Identifying the compounds that can distinguish between Saposhnikovia root and its substitute, Peucedanum ledebourielloides root, using LC-HR/MS metabolomics.

Sun, 26/04/2020 - 12:19
Related Articles Identifying the compounds that can distinguish between Saposhnikovia root and its substitute, Peucedanum ledebourielloides root, using LC-HR/MS metabolomics. J Nat Med. 2020 Apr 24;: Authors: Yoshitomi T, Wakana D, Uchiyama N, Tsujimoto T, Kawano N, Yokokura T, Yamamoto Y, Fuchino H, Hakamatsuka T, Komatsu K, Kawahara N, Maruyama T Abstract Previously, we established a 1H NMR metabolomics method using reversed-phase solid-phase extraction column (RP-SPEC), and succeeded in distinguishing wild from cultivated samples of Saposhnikoviae radix (SR), and between SR and its substitute, Peucedanum ledebourielloides root (PR). Herein, we performed LC-HR/MS metabolomics using fractions obtained via RP-SPEC to identify characteristic components of SR and PR. One and three characteristic components were respectively found for SR and PR; these components were isolated with their m/z values and retention times as a guide. The characteristic component of SR was identified as 4'-O-β-D-glucosyl-5-O-methylvisamminol (1), an indicator component used to identify SR in the Japanese Pharmacopoeia. In contrast, the characteristic components of PR were identified as xanthalin (2), 4'-O-β-D-apiosyl (1 → 6)-β-D-glucosyl-5-O-methylvisamminol (3), and 3'-O-β-D-apiosyl (1 → 6)-β-D-glucosylhamaudol (4) based on spectroscopic data such as 1D- and 2D-NMR, MS, and specific optical rotation. Among them, 4 is a novel compound. For the correlation between the NMR metabolomics results in the present and our previous report, only 1 and 2 were found to correlate with the chemical shifts, and the other compounds had no correlation. As the chemical shifts for compounds 1, 3, and 4 were similar to each other, especially for the aglycone moiety, they could not be distinguished because of the sensitivity and resolution of 1H NMR. Accordingly, combining NMR and LC/MS metabolomics with their different advantages is considered useful for metabolomics of natural products. The series of methods used in our reports could aid in quality evaluations of natural products and surveying of marker components. PMID: 32333306 [PubMed - as supplied by publisher]

Targeted metabolomics highlights perturbed metabolism in the brain of autism spectrum disorder sufferers.

Sun, 26/04/2020 - 12:19
Related Articles Targeted metabolomics highlights perturbed metabolism in the brain of autism spectrum disorder sufferers. Metabolomics. 2020 Apr 24;16(5):59 Authors: Graham SF, Turkoglu O, Yilmaz A, Ustun I, Ugur Z, Bjorndhal T, Han B, Mandal R, Wishart D, Bahado-Singh RO Abstract INTRODUCTION: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficiencies in social interactions and communication, combined with restricted and repetitive behavioral issues. OBJECTIVES: As little is known about the etiopathophysiology of ASD and early diagnosis is relatively subjective, we aim to employ a targeted, fully quantitative metabolomics approach to biochemically profile post-mortem human brain with the overall goal of identifying metabolic pathways that may have been perturbed as a result of the disease while uncovering potential central diagnostic biomarkers. METHODS: Using a combination of 1H NMR and DI/LC-MS/MS we quantitatively profiled the metabolome of the posterolateral cerebellum from post-mortem human brain harvested from people who suffered with ASD (n = 11) and compared them with age-matched controls (n = 10). RESULTS: We accurately identified and quantified 203 metabolites in post-mortem brain extracts and performed a metabolite set enrichment analyses identifying 3 metabolic pathways as significantly perturbed (p < 0.05). These include Pyrimidine, Ubiquinone and Vitamin K metabolism. Further, using a variety of machine-based learning algorithms, we identified a panel of central biomarkers (9-hexadecenoylcarnitine (C16:1) and the phosphatidylcholine PC ae C36:1) capable of discriminating between ASD and controls with an AUC = 0.855 with a sensitivity and specificity equal to 0.80 and 0.818, respectively. CONCLUSION: For the first time, we report the use of a multi-platform metabolomics approach to biochemically profile brain from people with ASD and report several metabolic pathways which are perturbed in the diseased brain of ASD sufferers. Further, we identified a panel of biomarkers capable of distinguishing ASD from control brains. We believe that these central biomarkers may be useful for diagnosing ASD in more accessible biomatrices. PMID: 32333121 [PubMed - as supplied by publisher]

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