PubMed

Related Articles Metabolism response of grazing yak to dietary concentrate supplementation in warm season. Animal. 2021 Feb 17;:100175 Authors: Xue BC, Zhang JX, Wang ZS, Wang LZ, Peng QH, Da LC, Bao SK, Kong XY, Xue B Abstract Supplementary feeding has a significant effect on the growth performance of grazing yaks. However, as far as is known, little information is available concerning how energy or protein feed supplementation affects the serum metabolome of grazing yaks during the warm season. We investigated the effects of supplementation with two different concentrates on the serum metabolome in grazing yaks using nuclear magnetic resonance spectroscopy in conjunction with multivariate data analysis. Twenty-four 2-year-old female yaks (133.04 ± 6.52 kg BW) were randomly divided into three groups and fed three different regimes (n = 8 per group): (1) grazing plus hull-less barley (HLB) supplementation, (2) grazing plus rapeseed meal (RSM) supplementation, and (3) grazing without supplementation. Both HLB and RSM supplementation significantly increased the average daily gain (ADG), and ADG under HLB supplementation was 11.9% higher (P < 0.05) than that of the RSM group. Supplementation markedly altered glucose, lipid, and protein metabolism, with the difference manifested as increased levels of some amino acids, acetyl-glycoproteins, low-density lipoproteins, and very low-density lipoproteins . Furthermore, the levels of 3-hydroxybutyrate, acetoacetate, and lactate metabolism were decreased. Serum metabolite changes in yaks in the HLB supplementation treatment differed from those in the RSM supplementation treatment; the difference was primarily manifested in lipid- and protein-related metabolites. We conclude that both the energy supplementation (HLB) and the protein supplementation (RSM) could remarkably promote the growth of yak heifers during the warm season, and the effect of energy supplementation was superior. Supplementary feeding changed the serum metabolite levels of yak heifers, indicating that such feeding could improve glucose's energy-supply efficiency and increase the metabolic intensity of lipids and proteins. Supplementation of yaks with HLB was more efficient in the promotion of yak glucose and protein anabolism compared to supplementation with RSM, while having a lesser effect on lipid metabolism. PMID: 33610519 [PubMed - as supplied by publisher]

Related Articles Heat treatment of bovine colostrum: effects on colostrum metabolome and serum metabolome of calves. Animal. 2021 Feb 17;:100180 Authors: Xu W, Mann S, Curone G, Kenéz Á Abstract Bovine colostrum is important for neonates' health due to its nutritive and non-nutritive components. Heat treatment of colostrum is a well-established management tool, but it may influence colostrum components and affect the health status of calves. In our previous studies, we had shown that colostrum proteome and serum proteome of calves were altered by heat treatment to different degrees. Our objectives in this study were to investigate the effects of heat treatment on colostrum metabolome and the effect of feeding heat-treated colostrum on the serum metabolome of newborn calves. Further, the changes in serum metabolome from before to after colostrum feeding were characterized. Newborn Holstein female calves (n = 10) were randomized within pairs and fed heat-treated (n = 5; 60 °C, 60 min) or raw (n = 5) colostrum at 8.5% of birth BW by esophageal feeder within 1 h of birth. After a single colostrum feeding, calves were not fed until after the 8 h time point. Blood samples were taken immediately prior to feeding (0 h) and 8 h after feeding. The colostrum and serum metabolome were first analyzed using reverse-phase chromatography and tandem MS, and serum metabolome was then further analyzed using hydrophilic interaction chromatography and tandem MS. In colostrum metabolome, 458 features were identified and 328 were annotated and a trend of separation between raw and heat-treated colostrum could be observed through multivariate analysis. In serum metabolome, 3 360 features were identified and 1 439 were annotated, but no trend of separation was observed between the two groups of calves fed raw colostrum vs. heat-treated colostrum. The serum metabolome presented substantial differences comparing before (0 h) and after colostrum feeding (8 h); in particular, a tripeptide, β-homovaline-β-homoalanine-β-homoleucine, and 1-(2-acetamido-2-deoxy-α-d-glucopyranosyl)-1D-myo-inositol had higher concentrations after colostrum feeding than before, along with other metabolites that were not fully annotated. Based on a relatively small sample size, our findings point to the effect of heat treatment on the change of colostrum metabolome, but not on the change of serum metabolome of calves fed raw colostrum vs. heat-treated colostrum. Further studies using larger sample size and complementary analytical techniques are warranted to further explore potential heat treatment-induced alterations in colostrum metabolome. PMID: 33610513 [PubMed - as supplied by publisher]

Related Articles Relaxometric learning: a pattern recognition method for T2 relaxation curves based on machine learning supported by an analytical framework. BMC Chem. 2021 Feb 20;15(1):13 Authors: Date Y, Wei F, Tsuboi Y, Ito K, Sakata K, Kikuchi J Abstract Nuclear magnetic resonance (NMR)-based relaxometry is widely used in various fields of research because of its advantages such as simple sample preparation, easy handling, and relatively low cost compared with metabolomics approaches. However, there have been no reports on the application of the T2 relaxation curves in metabolomics studies involving the evaluation of metabolic mixtures, such as geographical origin determination and feature extraction by pattern recognition and data mining. In this study, we describe a data mining method for relaxometric data (i.e., relaxometric learning). This method is based on a machine learning algorithm supported by the analytical framework optimized for the relaxation curve analyses. In the analytical framework, we incorporated a variable optimization approach and bootstrap resampling-based matrixing to enhance the classification performance and balance the sample size between groups, respectively. The relaxometric learning enabled the extraction of features related to the physical properties of fish muscle and the determination of the geographical origin of the fish by improving the classification performance. Our results suggest that relaxometric learning is a powerful and versatile alternative to conventional metabolomics approaches for evaluating fleshiness of chemical mixtures in food and for other biological and chemical research requiring a nondestructive, cost-effective, and time-saving method. PMID: 33610164 [PubMed]

Related Articles Short- and medium-term exposures of diazepam induce metabolomic alterations associated with the serotonergic, dopaminergic, adrenergic and aspartic acid neurotransmitter systems in zebrafish (Danio rerio) embryos/larvae. Comp Biochem Physiol Part D Genomics Proteomics. 2021 Feb 16;38:100816 Authors: Markin PA, Brito A, Moskaleva NE, Tagliaro F, Tarasov VV, La Frano MR, Savitskii MV, Appolonova SA Abstract INTRODUCTION: Diazepam is a well-known psychoactive drug widely used worldwide for the treatment of anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, sleeplessness, agitation, and pre/post-operative sedation. It is part of the benzodiazepine family, substances known to primarily act by binding and enhancing gamma-aminobutyric acid (GABAA) receptors. The objective of the present work was to investigate the influence of short and medium-term diazepam exposures on neurotransmitters measured through targeted metabolomics using a zebrafish embryo model. METHODS: Short-term (2.5 h) and medium-term (96 h) exposures to diazepam were performed at drug concentrations of 0.8, 1.6, 16, and 160 μg/L. Intervention groups were compared with a vehicle control group. Each group consisted of 20 zebrafish eggs/larvae. Metabolites related with neurotransmission were determined by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). RESULTS: Thirty-six compounds were quantified. Significantly increased tryptophan and serotonin concentrations were found in the intervention groups receiving higher doses of diazepam in 2.5 h exposure (p < 0.05 control versus intervention groups). Tyrosine concentrations were higher (p < 0.05) at higher concentrations in 2.5 h exposure, but lower (p < 0.05) at higher concentrations in 96 h exposure. Both phenylalanine and aspartic acid concentrations were higher (p < 0.05) at higher doses in 2.5 h and 96 h exposure. CONCLUSIONS: Short- and medium-term exposures to diazepam induce dose- and time-dependent metabolomic alterations associated with the serotonergic, dopaminergic/adrenergic, and aspartic acid neurotransmitter systems in zebrafish. PMID: 33610025 [PubMed - as supplied by publisher]

Related Articles Tissue-based metabolomics reveals metabolic biomarkers and potential therapeutic targets for esophageal squamous cell carcinoma. J Pharm Biomed Anal. 2021 Feb 05;197:113937 Authors: Chen Z, Gao Y, Huang X, Yao Y, Chen K, Zeng S, Mao W Abstract Prognosis for esophageal squamous cell carcinoma (ESCC) is poor, so it is essential to develop a more complete understanding of the disease. The purpose of this study was to explore metabolic biomarkers and potential therapeutic targets for ESCC. An ultra-high-performance liquid chromatography coupled with high resolution mass (UPLC/MS)-based metabolomic analysis was performed in 141 ESCC cancerous tissue samples and 70 non-cancerous counterparts. The results showed that 41 differential metabolites were annotated in the training set, and 37 were validated in the test set. Single-metabolite-based receiver operating characteristic (ROC) curves as well as metabolite-based machine learning models, including Partial Least Squares (PLS), Support Vector Machine (SVM), and Random Forest (RF), were investigated for cancerous and non-cancerous tissue classification. Six most prevalent diagnostic metabolites-adenylsuccinic acid, UDP-GalNAc, maleylacetoacetic acid, hydroxyphenylacetylglycine, galactose, and kynurenine-showed testing predictive accuracies of 0.89, 0.95, 0.97, 0.89, 0.84, and 0.84, respectively. Moreover, the metabolite-based models (PLS, SVM, and RF) had testing predictive accuracies of 0.95, 0.95, and 1.00, respectively. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis demonstrated that 2-hydroxymyristoylcarnitine (HR: 0.55, 95 % CI: 0.32 to 0.92), 3-hydroxyhexadecanoylcarnitine (HR: 0.49, 95 % CI: 0.29 to 0.83), and 2,3-Dinor-TXB1 (HR: 0.56, 95 % CI: 0.33 to 0.95) to be significantly associated with OS. Based on the observation of accumulation in amino acids, immunohistochemistry (IHC) staining revealed that the amino acid transporters SLC7A5/LAT1, SLC1A5/ASCT2, and SLC16A10/MCT10 were up-regulated in ESCC cancerous tissues when compared to non-cancerous equivalents. Consistently, the same panel of amino acids were downregulated in cells with SLC1A5 knockdown. Herein, it is concluded that this study not only identified several metabolites with diagnostic and/or prognostic value, but also provided accurate metabolite-based prediction models for ESCC tissue classification. Furthermore, the three up-regulated amino acid transporters were identified as potential therapeutic targets for ESCC, especially SLC1A5. PMID: 33609949 [PubMed - as supplied by publisher]

Related Articles Metabolic pathways of Chlorella sp. cells induced by exogenous spermidine against nitric oxide damage from coal-fired flue gas. Bioresour Technol. 2021 Feb 11;328:124827 Authors: Wang Z, Cheng J, Zhang X, Chen L, Liu J Abstract To protect microalgae that are used for photosynthetic CO2 fixation against high NO concentrations from coal-fired flue gas, 500 μM exogenous spermidine was added into Chlorella sp. solution resulting in an elevation of biomass yield by 30.5% under 327 ppm NO. Metabolomics, proteomics and enzyme activities were analyzed, revealing three effects of spermidine on Chlorella sp. resistance to NO stress. First, spermidine induced NO fixation in amino acids and their metabolites, mainly in form of 5-oxoproline (1.51-fold), which occurred through intracellular conversion reactions between citrulline and arginine. Accordingly, cellular respiration was strengthened along with a weakened NO inhibition, which enhanced active transport with ATP consumption. Second, spermidine guarded Chlorella sp. against peroxidation damage by improving activity of antioxidant enzymes. Finally, it protected the photosynthetic system of Chlorella sp. by increasing abundance of related enzymes to enhance carbon fixation. Thus exogenous spermidine improved biomass production against NO environment. PMID: 33609886 [PubMed - as supplied by publisher]

Related Articles The elucidation of the biodegradation of nitrobenzene and p-nitrophenol of nitroreductase from Antarctic psychrophile Psychrobacter sp. ANT206 under low temperature. J Hazard Mater. 2021 Feb 11;413:125377 Authors: Wang Y, Hou Y, Wang Q, Wang Y Abstract Psychrobacter is one important typical strain in the Antarctic environment. In our previous study, Psychrobacter sp. ANT206 from Antarctica with novel cold-adapted nitroreductase (PsNTR) could biodegrade nitrobenzene and p-nitrophenol in low temperature environment. In this study, the in-frame deletion mutant of psntr (Δpsntr-ANT206) that displayed well genetic stability and kanamycin resistance stability was constructed using allelic replacement method. Additionally, Δpsntr-ANT206 was more sensitive to nitrobenzene and p-nitrophenol in the comparison of heat and hyperosmolarity, suggesting that psntr gene participated in the regulation of the tolerance against nitro-aromatic compounds (NACs). Further analysis was conducted by integrated gas chromatography-mass spectrometry (GC-MS), and several metabolites were identified. Among them, ethylbenzene, L-Alanine, citric acid, aniline, 4-aminophenol and other metabolites were different between the wild-type strain and Δpsntr-ANT206 under nitrobenzene and p-nitrophenol stress at different time periods under low temperature, respectively. These data could increase the knowledge of the construction of deletion mutant strains and biodegradation mechanism of NACs of typical strains Psychrobacter from Antarctica, which would also provide the basis of the molecular technique on the regulation of bioremediation of the contaminants under low temperature in the future. PMID: 33609870 [PubMed - as supplied by publisher]

Related Articles Metabolite profiling, histological and oxidative stress responses in the grey mullet, Mugil cephalus exposed to the environmentally relevant concentrations of the heavy metal, Pb (NO3)2. Comp Biochem Physiol C Toxicol Pharmacol. 2021 Feb 17;:109004 Authors: Hajirezaee S, Ajdari A, Azhang B Abstract In this study, a metabolomics approach was applied to investigate the metabolic responses of grey mullet, Mugil cephalus to toxicity induced by heavy metal, Pb (NO3)2. In addition, the study was followed by assessing the peroxidation index and histology of liver as supplementary data. Pb (NO3)2 exposure affected the plasma metabolome, especially four group metabolites including amino acids, methylated metabolites, energetic metabolites and citric acid intermediates. Pb (NO3)2 in medium and high concentrations (15 and 25 μg/l) increased the levels of plasma amino acids compared to control (P < 0.01). In contrast, Pb (NO3)2 decreased the plasma levels of methylated metabolites (P < 0.01). The ketogenic metabolites and glycerol levels significantly elevated in fish exposed to 25 μg/l Pb (NO3)2 (P < 0.01). The plasma glucose levels increased in treatment, 5 μg/l Pb (NO3)2 and after a decline in treatment 15 μg/l Pb (NO3)2 elevated again in treatment 25 μg/l Pb (NO3)2 (P < 0.01).The plasma levels of lactate significantly increased in fish exposed to 5 and 15 μg/l Pb (NO3)2 and then declined to initial levels in treatment, 25 μg/l Pb (NO3)2 (P < 0.01). The plasma levels of TCA cycle intermediates significantly elevated in treatments 15 and 25 μg/l Pb (NO3)2 (P < 0.01). As a biomarker of oxidative stress, the plasma levels of malondialdehyde (MDA) showed significant increases in Pb (NO3)2 exposed fish (P < 0.01). During exposure period, wide ranges of liver tissue damages were also observed in Pb (NO3)2 exposed fish. In conclusion, exposure to Pb (NO3)2 affected the metabolome content of blood in grey mullet, mainly through inducing the biochemical pathways related to the metabolism of the amino acids, energetic metabolites and methylated metabolites. Our results may help to understand the effects of heavy metals on fish hematology from a molecular point of view. PMID: 33609749 [PubMed - as supplied by publisher]

Related Articles Serum Metabolomic Profiling Correlated with ISS and Clinical Outcome for Multiple Myeloma Patients Treated with High-dose Melphalan and Autologous Stem Cell Transplantation. Exp Hematol. 2021 Feb 17;: Authors: Veskovski L, Andersson PO, Turesson I, Malmodin D, Pedersen A, Mellqvist UH Abstract The metabolome, which is the final down-stream global product of metabolic processes in organisms, is not sufficiently described in multiple myeloma (MM) patients. The aim of this study was, therefore, to study the serum metabolomic profile using proton nuclear magnetic resonance (1H-NMR) spectroscopy, and its relationship to clinical characteristics and patient outcome. Serum samples, which were taken at diagnosis, from 201 MM patients who underwent high-dose melphalan followed by autologous stem cell transplantation (ASCT) as the first-line therapy, were analyzed. We found that the metabolomic profile differed between patients with different MM International Staging System (ISS) stages. The profile showed increased levels of cholesterol, phospholipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoproteins A1 and A2, valine, and leucine in ISS I patients compared with ISS III patients. The metabolomic profile also differed between patients with IgA and IgG paraprotein, predominantly because of higher levels of LDL and HDL subfractions in IgA patients. The exact pathway of metabolism leading to accumulation of these metabolites is still elusive, but this study shows an area of interest for further investigation in the search for new therapy targets and prognostic markers for this disease. PMID: 33609593 [PubMed - as supplied by publisher]

Related Articles LC-MS untargeted metabolomics assesses the delayed response of glufosinate treatment of transgenic glufosinate resistant (GR) buffalo grasses (Stenotaphrum secundatum L.). Metabolomics. 2021 Feb 20;17(3):28 Authors: Boonchaisri S, Rochfort S, Stevenson T, Dias DA Abstract INTRODUCTION: Glufosinate resistant (GR) buffalo grasses were genetically modified to resist the broad-spectrum herbicide, glufosinate by inserting a novel pat gene into its genome. This modification results in a production of additional phosphinothricin acetyltransferase (PAT) to detoxify the deleterious effects of glufosinate. The GR grasses and its associated herbicide form a modern, weeding program, to eradicate obnoxious weeds in turf lawn without damaging the grasses at relatively low costs and labor. As with several principal crops which are genetically modified to improve agricultural traits, biosafety of the GR buffalo grasses is inevitably expected to become a public concern. For the first time, we had previously examined the metabolome of glufosinate-resistant buffalo grasses, using a GC-MS untargeted approach to assess the risk of GR as well as identify any pleotropic effects arising from the genetically modification process. In this paper, an untargeted high-resolution LC-MS (LC-HRMS) untargeted metabolomics approach was carried out to complement our previous findings with respect to GR and wild type (WT) buffalo grasses. OBJECTIVE: One of the major aims of this present work was to compare GR to WT buffalo grasses by including the detection of the secondary metabolome and determine any unprecedented metabolic changes. METHODS: Eight-week old plants of 4 GR buffalo grasses, (93-1A, 93-2B, 93-3 C and 93-5A) and 3 wild type varieties (WT 8-4A, WT 9-1B and WT 9-1B) were submerged in either 5 % v/v of glufosinate or distilled water 3 days prior to a LC-HRMS based untargeted metabolomics analysis (glufosinate-treated or control, samples, respectively). An Ultra-High-Performance Liquid Chromatography (UHPLC) system coupled to a Velos Pro Orbitrap mass spectrometer system was employed to holistically measure the primary and secondary metabolome of both GR and WT buffalo grasses either treated with or without glufosinate and subsequently apply several bioinformatic tools including the automated pathway analysis algorithm, mummichog. RESULTS: LC-HRMS untargeted based metabolomics clearly identified that the global metabolite pools of both GR and WT cultivars were highly similar, providing strong, supporting evidence of substantial equivalence between the GR and WT varieties. These findings indicate that if any associated risks to these GR grasses were somehow present, the risk would be within those acceptable ranges present in the WT. Additionally, mummichog-based pathway analysis indicated that phenylalanine metabolism and the TCA cycle were significantly impacted by glufosinate treatment in the WT cultivar. It was possible that alterations in the relative concentrations of several intermediates in these pathways were likely due to glufosinate-induced production of secondary metabolites to enhance plant defense mechanisms against herbicidal stress at the expense of primary metabolism. CONCLUSIONS: GR buffalo grasses were found to be near identical to its WT comparator based on this complementary LC-HRMS based untargeted metabolomics. Therefore, these results further support the safe use of these GR buffalo grasses with substantial evidence. Interestingly, despite protected by PAT, GR buffalo grasses still demonstrated the response to glufosinate treatment by up-regulating some secondary metabolite-related pathways. PMID: 33609206 [PubMed - as supplied by publisher]

Related Articles Metabolic footprint of aging and obesity in red blood cells. Aging (Albany NY). 2021 Feb 19;13: Authors: Domingo-Ortí I, Lamas-Domingo R, Ciudin A, Hernández C, Herance JR, Palomino-Schätzlein M, Pineda-Lucena A Abstract Aging is a physiological process whose underlying mechanisms are still largely unknown. The study of the biochemical transformations associated with aging is crucial for understanding this process and could translate into an improvement of the quality of life of the aging population. Red blood cells (RBCs) are the most abundant cells in humans and are involved in essential functions that could undergo different alterations with age. The present study analyzed the metabolic alterations experienced by RBCs during aging, as well as the influence of obesity and gender in this process. To this end, the metabolic profile of 83 samples from healthy and obese patients was obtained by Nuclear Magnetic Resonance spectroscopy. Multivariate statistical analysis revealed differences between Age-1 (≤45) and Age-2 (>45) subgroups, as well as between BMI-1 (<30) and BMI-2 (≥30) subgroups, while no differences were associated with gender. A general decrease in the levels of amino acids was detected with age, in addition to metabolic alterations of glycolysis, the pentose phosphate pathway, nucleotide metabolism, glutathione metabolism and the Luebering-Rapoport shunt. Obesity also had an impact on the metabolomics profile of RBCs; sometimes mimicking the alterations induced by aging, while, in other cases, its influence was the opposite, suggesting these changes could counteract the adaptation of the organism to senescence. PMID: 33609087 [PubMed - as supplied by publisher]

Related Articles A metabolomics approach to evaluate post-fermentation enhancement of daidzein and genistein in a green okara extract. J Sci Food Agric. 2021 Feb 19;: Authors: Gupta S, Chen WN Abstract BACKGROUND: Okara is a major agri-industrial by-product of the tofu and soymilk industries. Employing food-wastes as substrates for the green production of natural functional compounds is a recent trend that addresses the dual concepts of sustainable production and a zero-waste ecosystem. RESULTS: Extracts of unfermented okara and okara fermented with Rhizopus oligosporus were obtained using ethanol as extraction solvent, coupled with ultrasound sonication for enhanced extraction. Fermented extracts yielded significantly better results for TPC and TFC than unfermented extracts. A qualitative LCQTOF/MS analysis revealed a shift from glucoside forms to respective aglycone forms of the detected isoflavones, post fermentation. Since the aglycone forms have been associated with numerous health benefits, a quantitative HPLC analysis was performed. Fermented okara extracts had daidzein and genistein concentrations of 11.782 ± 0.325 μg/mL and 10.125 ± 1.028 μg/mL, as opposed to that of 6.7 ± 2.42 μg/mL and 4.55 ± 0.316 μg/mL in raw okara extracts respectively. Lastly, the detected isoflavones were mapped to their metabolic pathways, to understand the biochemical reactions triggered during the fermentation process. CONCLUSION: Fermented okara may be implemented as a sustainable solution for production of natural bioactive isoflavonoids genistein and daidzein. This article is protected by copyright. All rights reserved. PMID: 33608899 [PubMed - as supplied by publisher]

Related Articles Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens. Cardiovasc Drugs Ther. 2021 Feb 20;: Authors: Gallogly S, Fujisawa T, Hung JD, Brittan M, Skinner EM, Mitchell AJ, Medine C, Luque N, Zodda E, Cascante M, Hadoke PW, Mills NL, Tura-Ceide O Abstract PURPOSE: Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. METHODS: In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. RESULTS: CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. CONCLUSIONS: CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes. PMID: 33608862 [PubMed - as supplied by publisher]

Related Articles The glycosyltransferase UGT76B1 modulates N-hydroxy-pipecolic acid homeostasis and plant immunity. Plant Cell. 2021 Jan 11;: Authors: Mohnike L, Rekhter D, Huang W, Feussner K, Tian H, Herrfurth C, Zhang Y, Feussner I Abstract The tradeoff between growth and defense is a critical aspect of plant immunity. Therefore, the plant immune response needs to be tightly regulated. Salicylic acid (SA) is an important plant hormone regulating defense against biotrophic pathogens. Recently, N-hydroxy-pipecolic acid (NHP) was identified as another regulator for plant innate immunity and systemic acquired resistance (SAR). Although the biosynthetic pathway leading to NHP formation is already been identified, how NHP is further metabolized is unclear. Here, we present UGT76B1 as a uridine diphosphate-dependent glycosyltransferase (UGT) that modifies NHP by catalyzing the formation of 1-O-glucosyl-pipecolic acid in Arabidopsis thaliana. Analysis of T-DNA and clustered regularly interspaced short palindromic repeats (CRISPR) knock-out mutant lines of UGT76B1 by targeted and nontargeted ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) underlined NHP and SA as endogenous substrates of this enzyme in response to Pseudomonas infection and UV treatment. ugt76b1 mutant plants have a dwarf phenotype and constitutive defense response which can be suppressed by loss of function of the NHP biosynthetic enzyme FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1). This suggests that elevated accumulation of NHP contributes to the enhanced disease resistance in ugt76b1. Externally applied NHP can move to distal tissue in ugt76b1 mutant plants. Although glycosylation is not required for the long-distance movement of NHP during SAR, it is crucial to balance growth and defense. PMID: 33608715 [PubMed - as supplied by publisher]

Related Articles Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings. Heart. 2021 Feb 19;: Authors: Iliou A, Mikros E, Karaman I, Elliott F, Griffin JL, Tzoulaki I, Elliott P Abstract Metabolomics, the comprehensive measurement of low-molecular-weight molecules in biological fluids used for metabolic phenotyping, has emerged as a promising tool to better understand pathways underlying cardiovascular disease (CVD) and to improve cardiovascular risk stratification. Here, we present the main methodologies for metabolic phenotyping, the methodological steps to analyse these data in epidemiological settings and the associated challenges. We discuss evidence from epidemiological studies linking metabolites to coronary heart disease and stroke. These studies indicate the systemic nature of CVD and identify associated metabolic pathways such as gut microbial cometabolism, branched-chain amino acids, glycerophospholipid and cholesterol metabolism, as well as activation of inflammatory processes. Integration of metabolomic with genomic data can provide new evidence for involved biochemical pathways and potential for causality using Mendelian randomisation. The clinical utility of metabolic biomarkers for cardiovascular risk stratification in healthy individuals has not yet been established. As sample sizes with high-dimensional molecular data increase in epidemiological settings, integration of metabolomic data across studies and platforms with other molecular data will lead to new understanding of the metabolic processes underlying CVD and contribute to identification of potentially novel preventive and pharmacological targets. Metabolic phenotyping offers a powerful tool in the characterisation of the molecular signatures of CVD, paving the way to new mechanistic understanding and therapies, as well as improving risk prediction of CVD patients. However, there are still challenges to face in order to contribute to clinically important improvements in CVD. PMID: 33608305 [PubMed - as supplied by publisher]

Related Articles CANTARE: finding and visualizing network-based multi-omic predictive models. BMC Bioinformatics. 2021 Feb 19;22(1):80 Authors: Siebert JC, Saint-Cyr M, Borengasser SJ, Wagner BD, Lozupone CA, Görg C Abstract BACKGROUND: One goal of multi-omic studies is to identify interpretable predictive models for outcomes of interest, with analytes drawn from multiple omes. Such findings could support refined biological insight and hypothesis generation. However, standard analytical approaches are not designed to be "ome aware." Thus, some researchers analyze data from one ome at a time, and then combine predictions across omes. Others resort to correlation studies, cataloging pairwise relationships, but lacking an obvious approach for cohesive and interpretable summaries of these catalogs. METHODS: We present a novel workflow for building predictive regression models from network neighborhoods in multi-omic networks. First, we generate pairwise regression models across all pairs of analytes from all omes, encoding the resulting "top table" of relationships in a network. Then, we build predictive logistic regression models using the analytes in network neighborhoods of interest. We call this method CANTARE (Consolidated Analysis of Network Topology And Regression Elements). RESULTS: We applied CANTARE to previously published data from healthy controls and patients with inflammatory bowel disease (IBD) consisting of three omes: gut microbiome, metabolomics, and microbial-derived enzymes. We identified 8 unique predictive models with AUC > 0.90. The number of predictors in these models ranged from 3 to 13. We compare the results of CANTARE to random forests and elastic-net penalized regressions, analyzing AUC, predictions, and predictors. CANTARE AUC values were competitive with those generated by random forests and  penalized regressions. The top 3 CANTARE models had a greater dynamic range of predicted probabilities than did random forests and penalized regressions (p-value = 1.35 × 10-5). CANTARE models were significantly more likely to prioritize predictors from multiple omes than were the alternatives (p-value = 0.005). We also showed that predictive models from a network based on pairwise models with an interaction term for IBD have higher AUC than predictive models built from a correlation network (p-value = 0.016). R scripts and a CANTARE User's Guide are available at https://sourceforge.net/projects/cytomelodics/files/CANTARE/ . CONCLUSION: CANTARE offers a flexible approach for building parsimonious, interpretable multi-omic models. These models yield quantitative and directional effect sizes for predictors and support the generation of hypotheses for follow-up investigation. PMID: 33607938 [PubMed - as supplied by publisher]

21 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 2021/02/20PubMed 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.

21 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 2021/02/20PubMed 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.

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 2021/02/19PubMed 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.

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 2021/02/18PubMed 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.