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 56 min ago

Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include A Compensatory Mechanism That Balances Fatty Acid β and ω Oxidation.

5 hours 58 min ago
Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include A Compensatory Mechanism That Balances Fatty Acid β and ω Oxidation. JPEN J Parenter Enteral Nutr. 2020 Jul 11;: Authors: Mendonça Machado N, Torrinhas RS, Sala P, Ishida RK, Guarda IFMS, Moura EGH, Sakai P, Santo MA, Linetzky Waitzberg D Abstract BACKGROUND: More than half patients underwent Roux-en-Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal metabolic mechanisms of this improvement are still elusive. METHODS: Paired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18) and ileum (n = 18), collected by double-balloon enteroscopy. RESULTS: After RYGB, improvements in body composition, weight-related and glucose homeostasis parameters were observed. Plasma enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid cycles, gluconeogenesis, malate-aspartate shuttle and carnitine synthesis. In gastrointestinal tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the tricarboxylic acid cycle (TCA) were enriched, particularly in plasma, jejunum and ileum. Fluctuations of dicarboxylic acids (DCA) were relevant in several metabolomic tests and metabolite alterations included aminomalonate and fumaric, malic, oxalic and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism. CONCLUSIONS: RYGB was associated with systemic and GI metabolic reprogramming. DCA alterations links ω and β fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement. This article is protected by copyright. All rights reserved. PMID: 32654184 [PubMed - as supplied by publisher]

RTExtract: Time-series NMR spectra quantification based on 3D surface ridge tracking.

5 hours 58 min ago
RTExtract: Time-series NMR spectra quantification based on 3D surface ridge tracking. Bioinformatics. 2020 Jul 12;: Authors: Wu Y, Judge MT, Arnold J, Bhandarkar SM, Edison AS Abstract MOTIVATION: Time-series NMR has advanced our knowledge about metabolic dynamics. Before analyzing compounds through modeling or statistical methods, chemical features need to be tracked and quantified. However, because of peak overlap and peak shifting, the available protocols are time consuming at best or even impossible for some regions in NMR spectra. RESULTS: We introduce RTExtract (Ridge Tracking based Extract), a computer vision-based algorithm, to quantify time-series NMR spectra. The NMR spectra of multiple time points were formulated as a 3D surface. Candidate points were first filtered using local curvature and optima, then connected into ridges by a greedy algorithm. Interactive steps were implemented to refine results. Among 173 simulated ridges, 115 can be tracked (RMSD < 0.001). For reproducing previous results, RTExtract took less than two hours instead of ∼48 hours, and two instead of seven parameters need tuning. Multiple regions with overlapping and changing chemical shifts are accurately tracked. AVAILABILITY: Source code is freely available within Metabolomics toolbox GitHub repository (https://github.com/artedison/Edison_Lab_Shared_Metabolomics_UGA/tree/master/metabolomics_toolbox/code/ridge_tracking) and is implemented in MATLAB and R. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID: 32653900 [PubMed - as supplied by publisher]

An integrative metabolomics and network pharmacology method for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba on anti-depression.

5 hours 58 min ago
An integrative metabolomics and network pharmacology method for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba on anti-depression. J Pharm Biomed Anal. 2020 Jul 02;189:113435 Authors: Zhang H, Zhang S, Hu M, Chen Y, Wang W, Zhang K, Kuang H, Wang Q Abstract Depression is a common mental illness, which is caused by 'liver qi stagnationin in traditional Chinese medicine (TCM) theory. Thus, relieving "liver qi stagnation" is considered to be effective at treating depression. The Radix Bupleuri and Radix Paeoniae Alba drug pair is the most classic compatible drug pair for mitigating a great variety of depression symptoms. However, its mechanisms remain largely unclear. In this study, metabolomics and network pharmacology methods were used to explore the potential mechanism of antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair. Analysis of metabolomics results showed that the drug pair can significantly improve CUMS-induced depression. The underlying mechanism of its antidepressant effect involves regulating the expression of brain-derived neurotrophic factors, inhibiting neurotoxicity, and regulating the HPA axis. Network pharmacology showed that drug pairs screened a total of 23 active ingredients and 63 targets, participated in the regulation of protein metabolism, Metabolism, Energy pathways, Cell growth and / or maintenance and other biological processes (BP), and mainly involved multiple signaling pathways and metabolic pathways to jointly exert antidepressant effects. Four related metabolic pathways regulated by the Radix Bupleuri and Radix Paeoniae Alba drug pair were input into the KEGG database to obtain the key genes of the related metabolic pathways. The predicted target of the network pharmacology was compared with the key genes of the metabolic pathway, and the common genes were screened: CYP1A1, CYP1A2; Western blot results showed that the drug pair up-regulated the protein expression of CYP1A1, CYP1A2. The medicine has an antidepressant effect by regulating the action of key enzymes. Metabolomics combined with network pharmacology research strategy revealed that antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair are characterized by multi-component, multi-target and multi-path mechanism of action. PMID: 32653815 [PubMed - as supplied by publisher]

Characterizing metabolites and potential metabolic pathways changes to understanding the mechanism of medicinal plant Phellodendri Amurensis cortex against doxorubicin-induced nephritis rats using UPLC-Q/TOF-MS metabolomics.

5 hours 58 min ago
Characterizing metabolites and potential metabolic pathways changes to understanding the mechanism of medicinal plant Phellodendri Amurensis cortex against doxorubicin-induced nephritis rats using UPLC-Q/TOF-MS metabolomics. J Pharm Biomed Anal. 2020 May 22;188:113336 Authors: Zhang H, Zhang S, Wang W, Wang Q, Kuang H, Wang Q Abstract Phellodendri Amurensis cortex (PAC), a famous traditional Chinese herb with good anti-inflammatory efficacy, is used to treat various liver and kidney sickness in clinical practice. However, the potential mechanisms protecting against nephritis of PAC have not been comprehensively elucidated. The aim of this research was to explore the mechanism of PAC against doxorubicin- induced nephritis in rats by characterizing metabolites and potential metabolic pathways changes. The rat models of nephritis were established using 6.5 mg/kg doxorubicin injection from caudal vein for five weeks. The rats in the treatment group were respectively received PAC extract at the dose of 216, 432, and 864 mg/kg once a day during the experiment. Then, urine metabolomics strategy based on ultra-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry (UPLC-Q/TOF-MS) has been employed to discover the possible significant metabolites and metabolic pathway of nephritis rats. At the end of the experiment, serum, urine and kidney tissue were collected for biochemical and pathological examination. The results showed that PAC treatment notably decreased urinary protein, serum Cr content and renal tissue lesions, and increased serum TP and ALB content. A total of potential twenty- eight metabolites such as 5'-methylthioadenosine, cGMP, dehydroepiandrosterone sulfate, salbuta, 2-phenylaminoadenosine contributing to nephritis rat model were selected and identified in the urine samples. Compared with the model group, the high-dose PAC group can recall 18 metabolites level, the medium-dose group can recall 13 metabolites level, and the low-dose PAC group can recall 8 metabolites level, which were involved in nine primary metabolic pathways such as steroid hormone biosynthesis, alanine,aspartate and glutamate metabolism, cysteine and methionine metabolism as well as glyoxylate and dicarboxylate metabolism. The protein expressions of key enzymes involving methylthioadenosine phosphorylase (Mtap), cytidine deaminase (Cda), thymidine kinase (Tk), argininosuccinate synthase (Ass) in metabolic pathways were further verified by Western blot. The results showed that Phellodendron chinense up-regulated the protein expressions of Cda and Tk and down-regulated the protein expressions of Mtap and Ass. In conclusion, PAC possesses renoprotective effect against doxorubicin-induced nephritis, which may be mediated via regulating differential metabolites, reducing oxidative stress response, improving renal function, enhancing the ability of the immune system, regulating the role of key enzymes. PMID: 32653762 [PubMed - as supplied by publisher]

Novel glucosinolate metabolism in larvae of the leaf beetle Phaedon cochleariae.

5 hours 58 min ago
Novel glucosinolate metabolism in larvae of the leaf beetle Phaedon cochleariae. Insect Biochem Mol Biol. 2020 Jul 09;:103431 Authors: Friedrichs J, Schweiger R, Geisler S, Mix A, Wittstock U, Müller C Abstract Plants of the Brassicales are defended by a binary system, in which glucosinolates are degraded by myrosinases, forming toxic breakdown products such as isothiocyanates and nitriles. Various detoxification pathways and avoidance strategies have been found that allow different herbivorous insect taxa to deal with the glucosinolate-myrosinase system of their host plants. Here, we investigated how larvae of the leaf beetle species Phaedon cochleariae (Coleoptera: Chrysomelidae), a feeding specialist on Brassicaceae, cope with this binary defence. We performed feeding experiments using leaves of watercress (Nasturtium officinale, containing 2-phenylethyl glucosinolate as major glucosinolate and myrosinases) and pea (Pisum sativum, lacking glucosinolates and myrosinases), to which benzenic glucosinolates (benzyl- or 4-hydroxybenzyl glucosinolate) were applied. Performing comparative metabolomics using UHPLC-QTOF-MS/MS, N-(phenylacetyl) aspartic acid, N-(benzoyl) aspartic acid and N-(4-hydroxybenzoyl) aspartic acid were identified as major metabolites of 2-phenylethyl-, benzyl- and 4-hydroxybenzyl glucosinolate, respectively, in larvae and faeces. This suggests that larvae of P. cochleariae metabolise isothiocyanates or nitriles to aspartic acid conjugates of aromatic acids derived from the ingested benzenic glucosinolates. Myrosinase measurements revealed activity only in second-instar larvae that were fed with watercress, but not in freshly moulted and starved second-instar larvae fed with pea leaves. Our results indicate that the predicted pathway can occur independently of the presence of plant myrosinases, because the same major glucosinolate-breakdown metabolites were found in the larvae feeding on treated watercress and pea leaves. A conjugation of glucosinolate-derived compounds with aspartic acid is a novel metabolic pathway that has not been described for other herbivores. PMID: 32653632 [PubMed - as supplied by publisher]

Insight into osteoarthritis through integrative analysis of metabolomics and transcriptomics.

5 hours 58 min ago
Insight into osteoarthritis through integrative analysis of metabolomics and transcriptomics. Clin Chim Acta. 2020 Jul 09;: Authors: Huang Z, He Z, Kong Y, Liu Z, Gong L Abstract Lack of clinically specific biomarkers has impeded the diagnosis of osteoarthritis (OA) and limited understanding of pathogenesis for OA has also restrained the enhancement of therapeutic measures. In the study, plasma untargeted metabolomics of twelve OA patients and twenty healthy controls (HC) were analyzed by gas chromatography coupled with quadrupole time-of-flight mass spectrometry (GC/Q-TOF-MS). The differential metabolites (DMs) between OA and HC were evaluated by multivariate analysis and Bayes discriminant analysis was employed to discover potential diagnosis biomarkers. Meanwhile a transcriptomic dataset GSE55235 was downloaded from GEO database to explore the differentially expressed genes (DEGs) between OA and HC by R/Bioconductor project. Finally, an integrative analysis of DMs and DEGs was performed to investigate the possible molecular mechanisms of OA. As a result, a panel of three metabolites including succinic acid, xanthurenic acid and L-tryptophan was revealed to potentially act as biomarker for the diagnosis of OA. Furthermore, the integrated analysis of metabolomics and transcriptomics showed the top three enrichment in the T cell receptor signaling pathway, Fc epsilon RI (FcεRI) signaling pathway, and thermogenesis, explaining the inflammation, joint destruction and energy metabolism disorders in OA. PMID: 32653484 [PubMed - as supplied by publisher]

IgG Fc N-glycosylation translates MHCII haplotype into autoimmune skin disease.

5 hours 58 min ago
IgG Fc N-glycosylation translates MHCII haplotype into autoimmune skin disease. J Invest Dermatol. 2020 Jul 09;: Authors: Clauder AK, Kordowski A, Bartsch YC, Köhl G, Lilienthal GM, Almeida LN, Lindemann T, Petry J, Rau CN, Gramalla-Schmitz A, Dühring L, Elbracht C, Kenno S, Tillmann J, Wuhrer M, Ludwig RJ, Ibrahim SM, Bieber K, Köhl J, Ehlers M, Manz RA Abstract The major histocompatibility complex (MHC)-haplotype represents the most prevalent genetic risk factor for the development of autoimmune diseases. However, the mechanisms by which MHC-associated genetic susceptibility translates into autoimmune disease are not fully understood. Epidermolysis bullosa acquisita (EBA) is an autoimmune skin blistering disease driven by autoantibodies to type VII collagen (COL7). Here, we investigated autoantigen-specific plasma cells, CD4+ T cells and IgG Fc-glycosylation in murine EBA in congenic mouse strains with the disease-permitting H2s or -non-permitting H2b MHCII haplotypes. Mice with an H2s haplotype showed increased numbers of autoreactive CD4+ T cells and elevated IL-21- and IFN-γ-production, associated with a higher frequency of IgG autoantibodies with an agalactosylated, proinflammatory N-glycan moiety. Mechanistically, we show that the altered antibody glycosylation leads to increased ROS release from neutrophils, the main driver of autoimmune inflammation in this model. These results indicate that MHCII-associated susceptibility to autoimmune diseases acuminates in a proinflammatory IgG Fc N-glycosylation pattern and provide a mechanistic link to increased ROS release by neutrophils. PMID: 32653301 [PubMed - as supplied by publisher]

Reply to: "Metabolomics to discriminate between acute decompensation and acute-on-chronic liver failure in cirrhosis".

5 hours 58 min ago
Reply to: "Metabolomics to discriminate between acute decompensation and acute-on-chronic liver failure in cirrhosis". J Hepatol. 2020 Jul 08;: Authors: Moreau R, Aguilar F, Arroyo V PMID: 32653223 [PubMed - as supplied by publisher]

TCF7L2 rs290487 C allele aberrantly enhances hepatic gluconeogenesis through allele-specific changes in transcription and chromatin binding.

Sun, 12/07/2020 - 12:46
TCF7L2 rs290487 C allele aberrantly enhances hepatic gluconeogenesis through allele-specific changes in transcription and chromatin binding. Aging (Albany NY). 2020 Jul 10;12: Authors: Zhang X, Ye P, Huang H, Wang B, Dong F, Ling Q Abstract In this study, we investigated the mechanisms underlying the altered hepatic glucose metabolism and enhanced diabetes risk in individuals with the TCF7L2 rs290487 C allele. Analysis of 195 cirrhotic patients revealed a higher insulin resistance index and incidence of hepatogenous diabetes in patients with the rs290487 C/C genotype compared to those with the C/T or T/T genotype. The in vitro experiments using targeted mutant PLC-PRF-5 cell line showed that cells with the rs290487 C/C genotype (C/C cells) had higher glucose production, lower glucose uptake, and lower TCF7L2 mRNA and protein levels than those with the C/T genotype (C/T cells). Integrated multi-omics analysis of ChIP-seq, ATAC-seq, RNA-seq, and metabolomics data showed genome-wide alterations in the DNA binding affinity of TCF7L2 in the C/C cells, including gain (e.g., PFKP and PPARGC1A) and loss (e.g., PGK1 and PGM1) of binding sites in several glucose metabolism-related genes. These allele-specific changes in transcriptional regulation lead to increased expression of gluconeogenesis-related genes (PCK1, G6PC and PPARGC1A) and their downstream metabolites (oxaloacetate and β-D-fructose 2,6-bisphosphate). These findings demonstrate that the TCF7L2 rs290487 C allele enhances gluconeogenesis through allele-specific changes in transcription and chromatin binding. PMID: 32651957 [PubMed - as supplied by publisher]

metabolomics; +29 new citations

Sat, 11/07/2020 - 15:35
29 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 2020/07/11PubMed 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; +29 new citations

Sat, 11/07/2020 - 12:32
29 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 2020/07/11PubMed 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; +24 new citations

Fri, 10/07/2020 - 15:18
24 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 2020/07/10PubMed 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; +24 new citations

Fri, 10/07/2020 - 12:18
24 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 2020/07/10PubMed 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; +24 new citations

Thu, 09/07/2020 - 15:05
24 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 2020/07/09PubMed 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; +28 new citations

Wed, 08/07/2020 - 14:42
28 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 2020/07/08PubMed 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; +21 new citations

Tue, 07/07/2020 - 14:30
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 2020/07/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Gut bacteria of the silkworm Bombyx mori facilitate host resistance against the toxic effects of organophosphate insecticides.

Mon, 06/07/2020 - 14:10
Gut bacteria of the silkworm Bombyx mori facilitate host resistance against the toxic effects of organophosphate insecticides. Environ Int. 2020 Jul 02;143:105886 Authors: Chen B, Zhang N, Xie S, Zhang X, He J, Muhammad A, Sun C, Lu X, Shao Y Abstract Organophosphate insecticides that are heavily used in agriculture for pest control have caused growing environmental problems and public health concerns worldwide. Ironically, insecticide resistance develops quickly in major lepidopteran pests, partially via their microbial symbionts. To investigate the possible mechanisms by which the microbiota confers insecticide resistance to Lepidoptera, the model organism silkworm Bombyx mori (Lepidoptera: Bombycidae) was fed different antibiotics to induce gut dysbiosis (microbiota imbalance). Larvae treated with polymyxin showed a significantly lower survival rate when exposed to chlorpyrifos. Through high-throughput sequencing, we found that the abundances of Stenotrophomonas and Enterococcus spp. changed substantially after treatment. To assess the roles played by these two groups of bacteria in chlorpyrifos resistance, a germ-free (GF) silkworm rearing protocol was established to avoid the influence of natural microbiota and antibiotics. Monoassociation of GF silkworms with Stenotrophomonas enhanced host resistance to chlorpyrifos, but not in Enterococcus-fed larvae, consistent with larval detoxification activity. GC-μECD detection of chlorpyrifos residues in feces indicated that neither Stenotrophomonas nor Enterococcus degraded chlorpyrifos directly in the gut. However, gut metabolomics analysis revealed a highly species-specific pattern, with higher levels of essential amino acid produced in the gut of silkworm larvae monoassociated with Stenotrophomonas. This critical nutrient provisioning significantly increased host fitness and thereby allowed larvae to circumvent the deleterious effects of these toxic chemicals more efficiently. Altogether, our study not only suggests a new mechanism for insecticide resistance in notorious lepidopteran pests but also provides a useful template for investigating the interplay between host and gut bacteria in complex environmental systems. PMID: 32623217 [PubMed - as supplied by publisher]

Metabolomics combined with proteomics provides a novel interpretation of the changes in nonvolatile compounds during white tea processing.

Mon, 06/07/2020 - 14:10
Metabolomics combined with proteomics provides a novel interpretation of the changes in nonvolatile compounds during white tea processing. Food Chem. 2020 Jun 24;332:127412 Authors: Chen Q, Shi J, Mu B, Chen Z, Dai W, Lin Z Abstract In this study, metabolomics and proteomics were employed to investigate the change mechanism of nonvolatile compounds during white tea processing. A total of 99 nonvolatile compounds were identified, among which the contents of 13 free amino acids, caffeine, theaflavins, 7 nucleosides and nucleotides, and 5 flavone glycosides increased significantly, while the contents of theanine, catechins, theasinesins, 3 proanthocyanidins, and phenolic acids decreased significantly during the withering period. The results of proteomics indicated that the degradation of proteins accounted for the increase in free amino acid levels; the weakened biosynthesis, in addition to oxidation, also contributed to the decrease in flavonoid levels; the degradation of ribonucleic acids contributed to the increase in nucleoside and nucleotide levels during the withering period. In addition, the drying process was found to slightly promote the formation of white tea taste. Our study provides a novel characterization of white tea taste formation during processing. PMID: 32623128 [PubMed - as supplied by publisher]

NK cells contribute to hepatic CD8+ T cell failure in hepatitis B virus-carrier mice after alcohol consumption.

Mon, 06/07/2020 - 14:10
NK cells contribute to hepatic CD8+ T cell failure in hepatitis B virus-carrier mice after alcohol consumption. Virus Res. 2020 Jul 02;:198085 Authors: Jiang S, Zhu Y, Cheng C, Li Y, Ma T, Peng Z, Li Q, Xu J, Xu L Abstract Despite the fact that both Hepatitis B virus (HBV) infection and excessive alcohol consumption represent health problems worldwide, the mechanism by which alcohol affected the progression of HBV-associated liver disease are not completely understood. Therefore, we studied how alcohol affects the development of HBV infection and the role of T cells and NK cells in the antiviral response. Mononuclear cells (MNCs) derived from HBV-carrier mice and wild type (WT) mice were characterized for phenotype by flow cytometry, HBV antigen and gene expression were detected by Radio Immunoassay (RIA), immunohistochemistry and quantitative real-time (qRT)-PCR. Metabolomics changes were detected in mice liver tissue based on ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS). The mice after ethanol consumption shows higher levels of HBV surface Ag (HBsAg), HBV core antigen (HBcAg) and HBV 3.5 kb RNA expression, and a lower level of CD8+ T cells during HBV persistence, with an increased lymphocyte activation gene-3 (LAG-3) expression on CD8+ T cell. In addition, the energy metabolism was downregulated and the oxidative stress was upregulated in the liver tissue. Furthermore, NK cells depletion results in a lower levels of HBV surface Ag (HBsAg) and HBV 3.5 kb RNA expression, and a higher level of CD8+ T cells with reduced expression of LAG-3. In conclusion, alcohol abuse induces CD8+ T cells failure after acute HBV infection, but depletion of NK cells could retore CD8+ T cell activity. Moreover, downregulation of energy metabolism and upregulation of oxidative stress may also contribute to CD8+ T cell failure. PMID: 32622853 [PubMed - as supplied by publisher]

Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study.

Mon, 06/07/2020 - 14:10
Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study. Microvasc Res. 2020 Jul 02;:104038 Authors: Erre GL, Mangoni AA, Passiu G, Bassu S, Castagna F, Carru C, Piga M, Zinellu A, Sotgia S Abstract BACKGROUND: The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known. METHODS: l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses. RESULTS: Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 μmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 μmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032]. CONCLUSIONS: ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group. PMID: 32622695 [PubMed - as supplied by publisher]

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