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

Phytochemical Profile and Biological Properties of Colchicum triphyllum (Meadow Saffron).

Sun, 12/04/2020 - 12:38
Related Articles Phytochemical Profile and Biological Properties of Colchicum triphyllum (Meadow Saffron). Foods. 2020 Apr 08;9(4): Authors: Senizza B, Rocchetti G, Okur MA, Zengin G, Yıldıztugay E, Ak G, Montesano D, Lucini L Abstract In this work, the phytochemical profile and the biological properties of Colchicum triphyllum (an unexplored Turkish cultivar belonging to Colchicaceae) have been comprehensively investigated for the first time. Herein, we focused on the evaluation of the in vitro antioxidant and enzyme inhibitory effects of flower, tuber, and leaf extracts, obtained using different extraction methods, namely maceration (both aqueous and methanolic), infusion, and Soxhlet. Besides, the complete phenolic and alkaloid untargeted metabolomic profiling of the different extracts was investigated. In this regard, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) allowed us to putatively annotate 285 compounds when considering the different matrix extracts, including mainly alkaloids, flavonoids, lignans, phenolic acids, and tyrosol equivalents. The most abundant polyphenols were flavonoids (119 compounds), while colchicine, demecolcine, and lumicolchicine isomers were some of the most widespread alkaloids in each extract analyzed. In addition, our findings showed that C. triphyllum tuber extracts were a superior source of both total alkaloids and total polyphenols, being on average 2.89 and 10.41 mg/g, respectively. Multivariate statistics following metabolomics allowed for the detection of those compounds most affected by the different extraction methods. Overall, C. triphyllum leaf extracts showed a strong in vitro antioxidant capacity, in terms of cupric reducing antioxidant power (CUPRAC; on average 96.45 mg Trolox Equivalents (TE)/g) and ferric reducing antioxidant power (FRAP) reducing power (on average 66.86 mg TE/g). Interestingly, each C. triphyllum methanolic extract analyzed (i.e., from tuber, leaf, and flower) was active against the tyrosinase in terms of inhibition, recording the higher values for methanolic macerated leaves (i.e., 125.78 mg kojic acid equivalent (KAE)/g). On the other hand, moderate inhibitory activities were observed against AChE and α-amylase. Strong correlations (p < 0.01) were also observed between the phytochemical profiles and the biological activities determined. Therefore, our findings highlighted, for the first time, the potential of C. triphhyllum extracts in food and pharmaceutical applications. PMID: 32276367 [PubMed - as supplied by publisher]

MOTA: Network-Based Multi-Omic Data Integration for Biomarker Discovery.

Sun, 12/04/2020 - 12:38
Related Articles MOTA: Network-Based Multi-Omic Data Integration for Biomarker Discovery. Metabolites. 2020 Apr 08;10(4): Authors: Fan Z, Zhou Y, Ressom HW Abstract The recent advancement of omic technologies provides researchers with the possibility to search for disease-associated biomarkers at the system level. The integrative analysis of data from a large number of molecules involved at various layers of the biological system offers a great opportunity to rank disease biomarker candidates. In this paper, we propose MOTA, a network-based method that uses data acquired at multiple layers to rank candidate disease biomarkers. The networks constructed by MOTA allow users to investigate the biological significance of the top-ranked biomarker candidates. We evaluated the performance of MOTA in ranking disease-associated molecules from three sets of multi-omic data representing three cohorts of hepatocellular carcinoma (HCC) cases and controls with liver cirrhosis. The results demonstrate that MOTA allows the identification of more top-ranked metabolite biomarker candidates that are shared by two different cohorts compared to traditional statistical methods. Moreover, the mRNA candidates top-ranked by MOTA comprise more cancer driver genes compared to those ranked by traditional differential expression methods. PMID: 32276350 [PubMed - as supplied by publisher]

A Protocol for the Multi-Omic Integration of Cervical Microbiota and Urine Metabolomics to Understand Human Papillomavirus (HPV)-Driven Dysbiosis.

Sun, 12/04/2020 - 12:38
Related Articles A Protocol for the Multi-Omic Integration of Cervical Microbiota and Urine Metabolomics to Understand Human Papillomavirus (HPV)-Driven Dysbiosis. Biomedicines. 2020 Apr 08;8(4): Authors: Chorna N, Godoy-Vitorino F Abstract The multi-omic integration of microbiota data with metabolomics has gained popularity. This protocol is based on a human multi-omics study, integrating cervicovaginal microbiota, HPV status and neoplasia, with urinary metabolites. Indeed, to understand the biology of the infections and to develop adequate interventions for cervical cancer prevention, studies are needed to characterize in detail the cervical microbiota and understand the systemic metabolome. This article is a detailed protocol for the multi-omic integration of cervical microbiota and urine metabolome to shed light on the systemic effects of cervical dysbioses associated with Human Papillomavirus (HPV) infections. This methods article suggests detailed sample collection and laboratory processes of metabolomics, DNA extraction for microbiota, HPV typing, and the bioinformatic analyses of the data, both to characterize the metabolome, the microbiota, and joint multi-omic analyses, useful for the development of new point-of-care diagnostic tests based on these approaches. PMID: 32276347 [PubMed - as supplied by publisher]

Protective Effect of Ocotillol, the Derivate of Ocotillol-Type Saponins in Panax Genus, against Acetic Acid-Induced Gastric Ulcer in Rats Based on Untargeted Metabolomics.

Sun, 12/04/2020 - 12:38
Related Articles Protective Effect of Ocotillol, the Derivate of Ocotillol-Type Saponins in Panax Genus, against Acetic Acid-Induced Gastric Ulcer in Rats Based on Untargeted Metabolomics. Int J Mol Sci. 2020 Apr 08;21(7): Authors: Wang C, Yuan Y, Pan H, Hsu AC, Chen J, Liu J, Li P, Wang F Abstract Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent. PMID: 32276345 [PubMed - as supplied by publisher]

metabolomics; +23 new citations

Sat, 11/04/2020 - 15:33
23 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 2020/04/11PubMed 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; +23 new citations

Sat, 11/04/2020 - 12:32
23 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 2020/04/11PubMed 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; +22 new citations

Fri, 10/04/2020 - 15:26
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 2020/04/10PubMed 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; +22 new citations

Fri, 10/04/2020 - 12:24
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 2020/04/10PubMed 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; +58 new citations

Thu, 09/04/2020 - 15:19
58 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 2020/04/09PubMed 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; +58 new citations

Thu, 09/04/2020 - 12:17
58 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 2020/04/09PubMed 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

Wed, 08/04/2020 - 15:07
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 2020/04/08PubMed 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

Wed, 08/04/2020 - 12:03
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 2020/04/08PubMed 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.

The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways.

Tue, 07/04/2020 - 14:43
The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways. iScience. 2020 Mar 21;23(4):101004 Authors: Sinha T, Naash MI, Al-Ubaidi MR Abstract The neural retina and retinal pigment epithelium (RPE) maintain a symbiotic metabolic relationship, disruption of which leads to debilitating vision loss. The current study was undertaken to identify the differences in the steady-state metabolite levels and the pathways functioning between bona fide neural retina and RPE. Global metabolomics and cluster analyses identified 650 metabolites differentially modulated between the murine neural retina and RPE. Of these, 387 and 163 were higher in the RPE and the neural retina, respectively. Further analysis coupled with transcript and protein level investigations revealed that under normal physiological conditions, the RPE utilizes the pentose phosphate (>3-fold in RPE), serine (>10-fold in RPE), and sphingomyelin biosynthesis (>5-fold in RPE) pathways. Conversely, the neural retina relied mostly on glycolysis. These results show how the RPE and the neural retina have acquired an efficient, complementary and metabolically diverse symbiotic niche to support each other's distinct functions. PMID: 32252018 [PubMed - as supplied by publisher]

Serum metabolomics-based reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury.

Tue, 07/04/2020 - 14:43
Serum metabolomics-based reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury. J Ethnopharmacol. 2020 Apr 03;: Authors: Yu C, Fu J, Guo L, Lian L, Yu D Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum Polysaccharide(GLP),traditional Chinese medicine (TCM) active ingredient, has a long history and has good curative effects on radiation injury. However, the mechanism of GLP treating radiation injury has not been clearly elucidated. THE AIM OF THE STUDY: This study was aimed to investigate the preventive effects of GLP on mice with radiation injury and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: Thirty mice were randomly divided into three groups. Namely 10 in the normal control group, the radiation model with normal saline and GLP group with GLP treatment(96 mg·kg-1)for 14 days, 2 h after 7th day after the intragastric administration, the model group and GLP group were subjected to whole body irradiation by X-rays except the normal control group. The peripheral blood WBC, RBC, HGB, PLT indicators.UPLC-Q-TOF-MS technique was used to analyze the serum of normal group, model group and GLP group, and to explore its potential key biomarkers and corresponding related metabolic pathways. RESULTS: The number of peripheral blood leukocytes (WBC) in the radiation model group was lower than that in the GLP group and the number of platelets (PLT) in the GLP group was significantly higher than that in the model group.Combined with the methods of principal component analysis (PCA), projection to latent structure-discrimination analysis (PLS-DA), three group were clearly distinguished from each other and 18 metabolites were identified as the potential biomarkers in the GLP treated mice. The identified biomarkers indicated that there were perturbations of the taurine and hypotaurine metabolism and glycerophospholipid metabolism. CONCLUSION: GLP can play a role in radiation protection by improving the expression of related potential biomarkers and related metabolic pathways in serum of radiation-induced mice. PMID: 32251760 [PubMed - as supplied by publisher]

Single and combined effects of the "Deadly trio" hypoxia, hypercapnia and warming on the cellular metabolism of the great scallop Pecten maximus.

Tue, 07/04/2020 - 14:43
Single and combined effects of the "Deadly trio" hypoxia, hypercapnia and warming on the cellular metabolism of the great scallop Pecten maximus. Comp Biochem Physiol B Biochem Mol Biol. 2020 Apr 03;:110438 Authors: Götze S, Bock C, Eymann C, Lannig G, Steffen JBM, Pörtner HO Abstract In the ocean the main climate drivers affecting marine organisms are warming, hypercapnia, and hypoxia. We investigated the acute effects of warming (W), warming plus hypercapnia (WHc, ~1800 μatm CO2), warming plus hypoxia (WHo, ~12.1 kPa O2), and a combined exposure of all three drivers (Deadly Trio, DT) on king scallops (Pecten maximus). All exposures started at 14 °C and temperature was increased by 2 °C once every 48 h until the lethal temperature was reached (28 °C). Gill samples were taken at 14 °C, 18 °C, 22 °C, and 26 °C and analyzed for their metabolic response by 1H-nuclear magnetic resonance (NMR) spectroscopy. Scallops were most tolerant to WHc and most susceptible to oxygen reduction (WHo and DT). In particular under DT, scallops' mitochondrial energy metabolism was affected. Changes became apparent at 22 °C and 26 °C involving significant accumulation of glycogenic amino acids (e.g. glycine and valine) and anaerobic end-products (e.g. acetic acid and succinate). In line with these observations the LT50 was lower under the exposure to DT (22.5 °C) than to W alone (~ 25 °C) indicating a narrowing of the thermal niche due to an imbalance between oxygen demand and supply. PMID: 32251734 [PubMed - as supplied by publisher]

Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment.

Tue, 07/04/2020 - 14:43
Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment. Mol Metab. 2020 Mar 13;:100976 Authors: Kappel BA, De Angelis L, Heiser M, Ballanti M, Stoehr R, Goettsch C, Mavilio M, Artati A, Paoluzi OA, Adamski J, Mingrone G, Staels B, Burcelin R, Monteleone G, Menghini R, Marx N, Federici M Abstract OBJECTIVE: The metabolic influence of gut microbiota plays a pivotal role in the pathogenesis of cardiometabolic diseases. Antibiotics affect intestinal bacterial diversity, and long-term usage has been identified as an independent risk factor for atherosclerosis-driven events. The aim of this study was to explore the interaction between gut dysbiosis by antibiotics and metabolic pathways with the impact on atherosclerosis development. METHODS: We combined oral antibiotics with different diets in an Apolipoprotein E-knockout mouse model linking gut microbiota to atherosclerotic lesion development via an integrative cross-omics approach including serum metabolomics and cecal 16S rRNA targeted metagenomic sequencing. We further investigated patients with carotid atherosclerosis compared to control subjects with comparable cardiovascular risk. RESULTS: Here, we show that increased atherosclerosis by antibiotics was connected to a loss of intestinal diversity and alterations of microbial metabolic functional capacity with a major impact on the host serum metabolome. Pathways were modulated by antibiotics and connected to atherosclerosis, which included diminished tryptophan and disturbed lipid metabolism. These pathways were related to the reduction of certain members of Bacteroidetes and Clostridia by antibiotics in the gut. Patients with atherosclerosis presented a similar metabolic signature as those induced by antibiotics in our mouse model. CONCLUSION: Taken together, this work provides insights into the complex interaction between intestinal microbiota and host metabolism. Our data highlight that detrimental effects of antibiotics on the gut flora are connected to a pro-atherogenic metabolic phenotype beyond classical risk factors. PMID: 32251665 [PubMed - as supplied by publisher]

Chemical Profiling and Characterization of Phenolic Acids, Flavonoids, Terpene Glycosides from Vangueria agrestis using Ultra-High Performance Liquid Chromatography/Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry and Metabolomics Approach.

Tue, 07/04/2020 - 14:43
Chemical Profiling and Characterization of Phenolic Acids, Flavonoids, Terpene Glycosides from Vangueria agrestis using Ultra-High Performance Liquid Chromatography/Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry and Metabolomics Approach. Biomed Chromatogr. 2020 Apr 06;:e4840 Authors: Avula B, Bae JY, Wang YH, Wang M, Osman AG, Smith K, Yuk J, Ali Z, Plumb R, Isaac G, Khan IA Abstract Vangueria agrestis is a shrub indigenous to tropical Africa, belonging to family Rubiaceae and traditionally is used as a decoction for treatment of fever, pain and malaria. The current study was undertaken to investigate the chemical constituents based on precursor exact mass and fragment ion information. The chemical profiling and structural characteristics of chemical constituents from methanolic extracts of dried aerial and roots of V. agrestis and dietary supplements were analyzed using UPLC-QToF coupled with UNIFI platform and multivariate analysis in both negative and positive ion modes. A non-targeted UPLC/MS analysis was carried out to profile the chemical constituents of crude extracts of V. agrestis and seventy-three compounds including reference compounds were identified. The fragments of flavonoids, monoterpene and triterpene glycosides revealed the characteristic cleavage of glycosidic linkages, and the fragmentation pattern provided identity of the sugars. This analytical method provides a fast method for quality assessment of dietary supplements. Finally, a chemometrics approach with multivariate statistical tools was used to visualize the differences between root and aerial parts of plant samples and to find the potential chemical markers that differentiate among these parts of V. agrestis samples and dietary supplements. PMID: 32251526 [PubMed - as supplied by publisher]

The scent of death: a metabolic goodbye signal emitted by dying cells.

Tue, 07/04/2020 - 14:43
The scent of death: a metabolic goodbye signal emitted by dying cells. Cell Death Differ. 2020 Apr 06;: Authors: Kroemer G, Pietrocola F PMID: 32251367 [PubMed - as supplied by publisher]

Comparative temporal metabolomics studies to investigate interspecies variation in three Ocimum species.

Tue, 07/04/2020 - 14:43
Comparative temporal metabolomics studies to investigate interspecies variation in three Ocimum species. Sci Rep. 2020 Mar 23;10(1):5234 Authors: Rastogi S, Shah S, Kumar R, Kumar A, Shasany AK Abstract Ocimum is one of the most revered medicinally useful plants which have various species. Each of the species is distinct in terms of metabolite composition as well as the medicinal property. Some basil types are used more often as an aromatic and flavoring ingredient. It would be informative to know relatedness among the species which though belong to the same genera while exclusively different in terms of metabolic composition and the operating pathways. In the present investigation the similar effort has been made in order to differentiate three commonly occurring Ocimum species having the high medicinal value, these are Ocimum sanctum, O. gratissimum and O. kilimandscharicum. The parameters for the comparative analysis of these three Ocimum species comprised of temporal changes in number leaf trichomes, essential oil composition, phenylpropanoid pathway genes expression and the activity of important enzymes. O. gratissimum was found to be richest in phenylpropanoid accumulation as well as their gene expression when compared to O. sanctum while O. kilimandscharicum was found to be accumulating terpenoid. In order to get an overview of this qualitative and quantitative regulation of terpenes and phenylpropenes, the expression pattern of some important transcription factors involved in secondary metabolism were also studied. PMID: 32251340 [PubMed - as supplied by publisher]

Atrazine biodegradation by mycoinsecticide Metarhizium robertsii: Insights into its amino acids and lipids profile.

Tue, 07/04/2020 - 14:43
Atrazine biodegradation by mycoinsecticide Metarhizium robertsii: Insights into its amino acids and lipids profile. J Environ Manage. 2020 May 15;262:110304 Authors: Szewczyk R, Różalska S, Mironenka J, Bernat P Abstract Atrazine, is one of major concern pesticides contaminating agricultural areas and ground water. Its microbial biodegradation seems to be the most efficient in terms of economic and environmental benefits. In the present work the cometabolic biodegradation of atrazine by the fungus Metarhizum robertsii IM 6519 during 10-day batch cultures was characterized. The herbicide was transformed to several hydroxy-, dechlorinated or dealkylated metabolites with the involvement of cytochrome P450 monooxygenases. The obtained metabolomics data revealed that atrazine induced oxidative stress (increased the levels of L-proline, L-ornithine, L-arginine, GABA and L-methionine), disruptions of the carbon and nitrogen metabolism (L-aspartic acid, L-asparagine, L-tyrosine, L-threonine, L-isoleucine, L-phenylalanine, 1-methyl-L-histidine, L-tryptophan, L-valine, L-alanine, O-phospho-L-serine, L-sarcosine or L-lysine) and caused an increase in the membrane fluidity (a rise in the phosphatidylcholines/phosphatidylethanolamines (PC/PE) ratio together with the growth of the taurine level). The increased level of hydroxyl derivatives of linoleic acid (9-HODE and 13-HODE) confirmed that atrazine induced lipid peroxidation. The presented results suggesting that M. robertsii IM 6519 might be applied in atrazine biodegradation and may bring up the understanding of the process of triazine biodegradation by Metarhizum strains. PMID: 32250788 [PubMed - as supplied by publisher]

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