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: 2 hours 38 sec ago

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]

Plasma Metabolomic Markers of Insulin Resistance and Diabetes and Rate of Incident Parkinson's Disease.

Tue, 07/04/2020 - 14:43
Plasma Metabolomic Markers of Insulin Resistance and Diabetes and Rate of Incident Parkinson's Disease. J Parkinsons Dis. 2020 Mar 31;: Authors: Molsberry S, Bjornevik K, Hughes KC, Zhang ZJ, Jeanfavre S, Clish C, Healy B, Schwarzschild M, Ascherio A Abstract BACKGROUND: Although there is evidence of shared dysregulated pathways between diabetes and Parkinson's disease, epidemiologic research on an association between the two diseases has produced inconsistent results. OBJECTIVE: We aimed to assess whether known metabolomic markers of insulin resistance and diabetes are also associated with Parkinson's disease development. METHODS: We conducted a nested case-control study among Nurses' Health Study and Health Professionals Follow-up Study participants who had provided blood samples up to twenty years prior to Parkinson's diagnosis. Cases were matched to risk-set sampled controls by age, sex, fasting status, and time of blood collection. Participants provided covariate information via regularly collected cohort questionnaires. We used conditional logistic regression models to assess whether plasma levels of branched chain amino acids, acylcarnitines, glutamate, or glutamine were associated with incident development of Parkinson's disease. RESULTS: A total of 349 case-control pairs were included in this analysis. In the primary analyses, none of the metabolites of interest were associated with Parkinson's disease development. In investigations of the association between each metabolite and Parkinson's disease at different time intervals prior to diagnosis, some metabolites showed marginally significant association but, after correction for multiple testing, only C18 : 2 acylcarnitine was significantly associated with Parkinson's disease among subjects for whom blood was collected less than 60 months prior to case diagnosis. CONCLUSIONS: Plasma levels of diabetes-related metabolites did not contribute to predict risk of Parkinson's disease. Further investigation of the relationship between pre-diagnostic levels of diabetes-related metabolites and Parkinson's disease in other populations is needed to confirm these findings. PMID: 32250318 [PubMed - as supplied by publisher]

An extracytoplasmic protein and a moonlighting enzyme modulate synthesis of c-di-AMP in Listeria monocytogenes.

Tue, 07/04/2020 - 14:43
An extracytoplasmic protein and a moonlighting enzyme modulate synthesis of c-di-AMP in Listeria monocytogenes. Environ Microbiol. 2020 Apr 06;: Authors: Gibhardt J, Heidemann JL, Bremenkamp R, Rosenberg J, Seifert R, Kaever V, Ficner R, Commichau FM Abstract The second messenger cyclic di-AMP (c-di-AMP) is essential for growth of many bacteria because it controls osmolyte homeostasis. c-di-AMP can regulate the synthesis of potassium uptake systems in some bacteria and also directly inhibits and activates potassium import and export systems, respectively. Therefore, c-di-AMP production and degradation have to be tightly regulated depending on the environmental osmolarity. The Gram-positive pathogen Listeria monocytogenes relies on the membrane-bound diadenylate cyclase CdaA for c-di-AMP production and degrades the nucleotide with two phosphodiesterases. While the enzymes producing and degrading the dinucleotide have been reasonably well examined, the regulation of c-di-AMP production is not well understood yet. Here we demonstrate that the extracytoplasmic regulator CdaR interacts with CdaA via its transmembrane helix to modulate c-di-AMP production. Moreover, we show that the phosphoglucosamine mutase GlmM forms a complex with CdaA and inhibits the diadenylate cyclase activity in vitro. We also found that GlmM inhibits c-di-AMP production in L. monocytogenes when the bacteria encounter osmotic stress. Thus, GlmM is the major factor controlling the activity of CdaA in vivo. GlmM can be assigned to the class of moonlighting proteins because it is active in metabolism and adjusts the cellular turgor depending on environmental osmolarity. This article is protected by copyright. All rights reserved. PMID: 32250026 [PubMed - as supplied by publisher]

Metabolomic alternations of follicular fluid of obese women undergoing in-vitro fertilization treatment.

Tue, 07/04/2020 - 14:43
Metabolomic alternations of follicular fluid of obese women undergoing in-vitro fertilization treatment. Sci Rep. 2020 Apr 06;10(1):5968 Authors: Song J, Xiang S, Pang C, Guo J, Sun Z Abstract Obesity exerts negative effects on the metabolic homeostasis of cells in various tissues, but how it influences ovum metabolism is not fully understood. Previous studies demonstrate that oocyte genes that regulate oxidative stress, lipid metabolism, and inflammation are highly expressed in obese women. However, the metabolic effects of these genetic variations are not clear. To address this gap, we conducted an exploratory evaluation of follicular fluid (FF) metabolites in underweight, normal-weight, overweight, and obese women undergoing in vitro fertilization (IVF) treatment. The FF samples from the underweight (Group A, n = 40), normal-weight (Group B, n = 40), overweight (Group C, n = 40), and obese women (Group D, n = 40) were analyzed using ultra-performance liquid chromatography high-resolution mass spectrometry. A novel, high-coverage, semi-targeted metabolomics method (SWATH to MRM) and a targeted metabolomics method were employed to identify and verify the differential metabolites between the four groups. Sixteen differentially expressed FF metabolites were identified. Increase of BMI was associated with upregulation of 5 metabolites, ganoderiol H, LPI (18:3), sedoheptulose 1,7-bisphosphate, austalide L and 2 - {[hydroxyl (3-hydroxy-4-methoxyphenylmethylidene] amino} acetic acid, and downregulation of 5 metabolites, 1-phenyl-1,3-elcosanedione, retinol acetate, p-Cresol sulfate, setariol and arachidonyl carnitine. These metabolites were enriched in different metabolic pathways of retinol metabolism and fatty acid metabolism. These obesity-related differential metabolites provide a pathogenesis mechanism that explains the decline of oocyte development during obesity. These results suggest that obesity affects follicular environment prior to pregnancy, a time-window that may be important for lifestyle interventions to decrease obesity levels. PMID: 32249791 [PubMed - in process]

Mass spectrometry-based Food Metabolomics in Routine Applications: A basic Standardization Approach using Housekeeping Metabolites for the Authentication of Asparagus.

Tue, 07/04/2020 - 14:43
Mass spectrometry-based Food Metabolomics in Routine Applications: A basic Standardization Approach using Housekeeping Metabolites for the Authentication of Asparagus. J Agric Food Chem. 2020 Apr 04;: Authors: Creydt M, Fischer M Abstract The low reproducibility of non-targeted LC-MS-based metabolomics approaches represents a major challenge for their implementation in routine analyses, since it is impossible to compare individual measurements directly with each other, if they were not analysed in the same batch. This study describes a normalization process based on housekeeping metabolites in plant based raw materials, which are present in comparatively constant concentrations and are subject to no or only minor deviations due to exogenous influences. As a model, an authenticity study was selected to determine the origin of white asparagus (asparagus officinalis). Using three model data sets and one test data set, we were able to show that samples that have been measured independently of one another can be correctly assigned in terms of origin after the normalization with housekeeping metabolites. The procedure does not require internal standards or the measurements of further reference samples and can also be applied to other matrices and scientific issues. PMID: 32249560 [PubMed - as supplied by publisher]

Analyses of competent and non-competent subpopulations of Bacillus subtilis reveal yhfW, yhxC and ncRNAs as novel players in competence.

Tue, 07/04/2020 - 14:43
Related Articles Analyses of competent and non-competent subpopulations of Bacillus subtilis reveal yhfW, yhxC and ncRNAs as novel players in competence. Environ Microbiol. 2020 Apr 05;: Authors: Boonstra M, Schaffer M, Sousa J, Morawska L, Holsappel S, Hildebrandt P, Sappa PK, Rath H, de Jong A, Lalk M, Mäder U, Völker U, Kuipers OP Abstract Upon competence-inducing nutrient-limited conditions only part of the B. subtilis population becomes competent. Here, we separated the two sub-populations by Fluorescence Assisted Cell Sorting (FACS). Using RNA-seq we confirmed the previously described ComK regulon. We also found for the first time significantly down-regulated genes in the competent sub-population. The down-regulated genes are not under direct control by ComK, but have higher levels of corresponding antisense RNAs in the competent subpopulation. During competence, cell-division and replication are halted. By investigating the proteome during competence we found higher levels of the regulators of cell division, MinD and Noc. The exonucleases SbcC and SbcD were also primarily regulated at the post-transcriptional level. In the competent sub-population yhfW was newly identified as being highly up-regulated. Its absence reduces the expression of comG, and has a modest, but statistically significant effect on the expression of comK. Although expression of yhfW is higher in the competent subpopulation, no ComK-binding site is present in its promoter region. Mutants of yhfW have a small but significant defect in transformation. Metabolomic analyses revealed significant reductions in tricarboxylic acid (TCA) cycle metabolites and several amino acids in a ΔyhfW mutant. RNA-seq analysis of ΔyhfW revealed higher expression of the NAD synthesis genes nadA, nadB and nadC. This article is protected by copyright. All rights reserved. PMID: 32249531 [PubMed - as supplied by publisher]

Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes.

Tue, 07/04/2020 - 14:43
Related Articles Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes. Cancer Discov. 2020 Apr 05;: Authors: Ochi Y, Kon A, Sakata T, Nakagawa MM, Nakazawa N, Kakuta M, Kataoka K, Koseki H, Nakayama M, Morishita D, Tsuruyama T, Saiki R, Yoda A, Okuda R, Yoshizato T, Yoshida K, Shiozawa Y, Nannya Y, Kotani S, Kogure Y, Kakiuchi N, Nishimura T, Makishima H, Malcovati L, Yokoyama A, Takeuchi K, Sugihara E, Sato TA, Sanada M, Takaori-Kondo A, Cazzola M, Kengaku M, Miyano S, Shirahige K, Suzuki HI, Ogawa S Abstract STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant co-mutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between Stag2 and Runx1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. Combined loss of Stag2 and Runx1, which co-localize at enhancer-rich, Ctcf-deficient sites, synergistically attenuates enhancer-promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPCs) and myelodysplastic syndromes (MDS). Attenuated enhancer-promoter loops in Stag2/Runx1-deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for regulation of HSPCs. Down-regulation of high-pausing genes is also confirmed in STAG2/cohesin-mutated primary leukemia samples. Our results highlight a unique STAG2/RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis. PMID: 32249213 [PubMed - as supplied by publisher]

Quorum sensing inhibition and tobramycin acceleration in Chromobacterium violaceum by two natural cinnamic acid derivatives.

Mon, 06/04/2020 - 14:34
Related Articles Quorum sensing inhibition and tobramycin acceleration in Chromobacterium violaceum by two natural cinnamic acid derivatives. Appl Microbiol Biotechnol. 2020 Apr 04;: Authors: Cheng WJ, Zhou JW, Zhang PP, Luo HZ, Tang S, Li JJ, Deng SM, Jia AQ Abstract Chromobacterium violaceum, one free-living Gram-negative bacterium, is abundantly presented in tropics and sub-tropics soil and aquatic environment; it is also an opportunistic human pathogen. Here, two cinnamic acid derivatives, i.e., 4-dimethylaminocinnamic acid (DCA) and 4-methoxycinnamic acid (MCA), were identified as potential quorum sensing (QS) and biofilm inhibitors in C. violaceum ATCC12472. Both DCA (100 μg/mL) and MCA (200 μg/mL) inhibited the levels of N-decanoyl-homoserine lactone (C10-HSL) and reduced the production of certain virulence factors in C. violaceum, including violacein, hemolysin, and chitinase. Metabolomics analysis indicated that QS-related metabolites, such as ethanolamine and L-methionine, were down-regulated after treatment with DCA and MCA. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that DCA and MCA markedly suppressed the expression of two QS-related genes (cviI and cviR). In addition, DCA and MCA also inhibited biofilm formation and enhanced the susceptibility of biofilms to tobramycin, which was evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Our results indicated that DCA and MCA can serve as QS-based agent for controlling pathogens.Key Points • DCA and MCA inhibited QS and biofilm formation in C. violaceum.• The combination of DCA or MCA and tobramycin removed the preformed biofilm of C. violaceum. • DCA or MCA inhibited virulence factors and expressions of cviI and cviR of C. violaceum.• DCA or MCA are potential antibiotic accelerants for treating C. violaceum infection. PMID: 32248442 [PubMed - as supplied by publisher]

Deciphering the mechanism of carbon sources inhibiting recolorization in the removal of refractory dye: Based on an untargeted LC-MS metabolomics approach.

Mon, 06/04/2020 - 14:34
Related Articles Deciphering the mechanism of carbon sources inhibiting recolorization in the removal of refractory dye: Based on an untargeted LC-MS metabolomics approach. Bioresour Technol. 2020 Mar 24;307:123248 Authors: Zheng X, Xie X, Liu Y, Cong J, Fan J, Fang Y, Liu N, He Z, Liu J Abstract In this study, the biological decolorization of reactive black 5 (RB5) by Klebsiella sp. KL-1 in yeast extract (YE) medium was captured the recolorization after exposure to O2, which induced a 15.82% reduction in decolorization efficiency. Similar result was also observed in YE + lactose medium, but not in YE + glucose/xylose media (groups YE + Glu/Xyl). Through biodegradation studies, several degradation intermediates without quinoid structure were produced in groups YE + Glu/Xyl and differential degradation pathways were deduced in diverse groups. Metabolomics analysis revealed significant variations in up-/down-regulated metabolites using RB5 and different carbon sources. Moreover, the underlying mechanism of recolorization inhibition was proposed. Elevated reducing power associated with variable metabolites (2-hydroxyhexadecanoic acid, 9(R)-HODE cholesteryl ester, linoleamide, oleamide) rendered additional reductive cleavage of C-N bond on naphthalene ring. This study provided a new orientation to inhibit recolorization and deepened the understanding of the molecular mechanism of carbon sources inhibiting recolorization in the removal of refractory dyes. PMID: 32248066 [PubMed - as supplied by publisher]

Liraglutide attenuates renal tubular ectopic lipid deposition in rats with diabetic nephropathy by inhibiting lipid synthesis and promoting lipolysis.

Mon, 06/04/2020 - 14:34
Related Articles Liraglutide attenuates renal tubular ectopic lipid deposition in rats with diabetic nephropathy by inhibiting lipid synthesis and promoting lipolysis. Pharmacol Res. 2020 Apr 02;:104778 Authors: Su K, Yi B, Yao BQ, Xia T, Yang YF, Zhang ZH, Chen C Abstract Liraglutide is a new hypoglycemic drug. The previous studies have shown that liraglutide can improve the renal outcomes of patients with type 2 diabetes. Recently, it was approved by the U.S. FDA for used as a weight-loss drugs. However, the mechanism of its improvements of renal function in diabetic nephropathy patients is unclear. In addition, the effect of liraglutide on lipid metabolism is also not clear. The purpose of this study was to investigate the effects and mechanisms of liraglutide in alleviating ectopic lipid deposition (ELD) in rats with diabetic nephropathy (DN). Male Sprague-Dawley (SD) rats were treated with high-fat diet + unilateral nephrectomy + low-dose STZ combined to establish a DN rat model to evaluate the lipid-lowering effect of liraglutide. Liraglutide at 0.4 mg/kg/d were subcutaneous injected into for 12 weeks (DN + liraglutide group). After the DN rat model was established, body weight loss, 24-h urine volume increasing, serum triglycerides (TG) and serum total cholesterol (TCh) increasing, ectopic lipid droplet deposition in renal tubular increasing, mesangial proliferation in renal tissue were observed in DN rats. The treatment with liraglutide could reduce the body weight and the average daily food intake of the rats, as well as TG, TCh, and ectopic lipid droplet deposition in renal tubular. Metabolomics result showed that serum differential metabolites between the DN - vehicle control group and the DN + liraglutide group mainly included serine, threonine, phenylalanine, oxyproline, threonine, sorbitol, glyceryl monostearate, glycerol monostearate, and β-d-glucuronic acid. Moreover, liraglutide can reduce plasma lipid levels in DN rats by increasing the products of lipolysis including 1-monopalmitin and 1-monoostearin. Immunohistochemistry and Western blot showed that the expression levels of lipid synthesis-related sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase (FAS) were significantly increased, and lipolysis-related adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were significantly decreased both in the renal tissue of DN rats and PA-induced HK-2 cells (lipid droplet accumulation model). However, liraglutide can attenuate renal tubular ectopic lipid deposition in DN rats by inhibiting SREBP-1, FAS and increasing ATGL, HSL protein expression level, and also ameliorated PA-induced lipid accumulation in renal tubular epithelial cells. These lipid metabolism changes were attributed to liraglutide by upregulating AMP-activated protein kinase (AMPK) phosphorylation in the kidney of DN rats. Collectively, these findings confirm that liraglutide inhibits lipid synthesis and promotes lipolysis to attenuate renal ectopic lipid deposition in DN rats by promoting AMPK phosphorylation. PMID: 32247822 [PubMed - as supplied by publisher]

Olive oil by-product as functional ingredient in bakery products. Influence of processing and evaluation of biological effects.

Mon, 06/04/2020 - 14:34
Related Articles Olive oil by-product as functional ingredient in bakery products. Influence of processing and evaluation of biological effects. Food Res Int. 2020 May;131:108940 Authors: Di Nunzio M, Picone G, Pasini F, Chiarello E, Caboni MF, Capozzi F, Gianotti A, Bordoni A Abstract Nowadays, the strong demand for adequate nutrition is accompanied by concern about environmental pollution and there is a considerable emphasis on the recovery and recycling of food by-products and wastes. In this study, we focused on the exploitation of olive pomace as functional ingredient in biscuits and bread. Standard and enriched bakery products were made using different flours and fermentation protocols. After characterization, they were in vitro digested and used for supplementation of intestinal cells (Caco-2), which underwent exogenous inflammation. The enrichment caused a significant increase in the phenolic content in all products, particularly in the sourdough fermented ones. Sourdough fermentation also increased tocol concentration. The increased concentration of bioactive molecules did not reflect the anti-inflammatory effect, which was modulated by the baking procedure. Conventionally fermented bread enriched with 4% pomace and sourdough fermented, not-enriched bread had the greatest anti-inflammatory effect, significantly reducing IL-8 secretion in Caco-2 cells. The cell metabolome was modified only after supplementation with sourdough fermented bread enriched with 4% pomace, probably due to the high concentration of tocopherol that acted synergistically with polyphenols. Our data highlight that changes in chemical composition cannot predict changes in functionality. It is conceivable that matrices (including enrichment) and processing differently modulated bioactive bioaccessibility, and consequently functionality. PMID: 32247504 [PubMed - as supplied by publisher]

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