• MeSH
• hepatitida C diagnóza   genetika   virologie   MeSH
• leukocyty mononukleární genetika   MeSH
• lidé MeSH
• polymerázová řetězová reakce metody   MeSH
• RNA virová genetika   MeSH
• Check Tag
• lidé MeSH

• MeSH
• buněčné dělení účinky léků   MeSH
• kultivované buňky MeSH
• leukocyty mononukleární fyziologie   účinky léků   MeSH
• lidé MeSH
• lyofilizace MeSH
• melanom MeSH
• protinádorové vakcíny MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• amplifikace genu MeSH
• Hepacivirus MeSH
• kultivované buňky MeSH
• leukocyty mononukleární MeSH
• replikace viru MeSH
• viremie MeSH

Telomeres are repetitive DNA located at the ends of chromosomes that preserve genomic stability. Excessive leukocyte telomere shortening is associated with cardio-metabolic disease and increased mortality risk. Although most studies indicate exercise training could attenuate leukocyte telomere attrition, data is somewhat equivocal. The inconsistencies could be partly explained by the different populations of leukocytes isolated for telomere length assessment. Accordingly, average peripheral blood mononuclear cell (PBMC) and whole blood leukocyte telomere length were assessed in 44 endurance athletes and 40 healthy controls using quantitative PCR. While whole blood leukocyte telomeres were, on average, 6.1% longer in endurance athletes compared to controls, PBMC telomere length was similar between the two cohorts in age and sex-adjusted analyses (athletes vs controls, mean T/S ratio ± SE: 3.25 ± 0.05 vs 3.23 ± 0.05, p = 0.72). Other than a weak inverse correlation with sitting (r = −0.25, p = 0.03), no statistically significant correlations were found between PBMC telomere length and exercise parameters. Unlike whole blood leukocytes, PBMC telomere length is not associated with endurance exercise and exercise parameters. These findings suggest the need for future work to quantify short and long telomeres of sorted immune cell populations and to measure them in context with cell counts and exercise traits.

• MeSH
• leukocyty mononukleární cytologie   fyziologie   MeSH
• lidé MeSH
• pohybová aktivita MeSH
• senioři MeSH
• spotřeba kyslíku MeSH
• srdeční frekvence MeSH
• stárnutí buněk MeSH
• stárnutí MeSH
• tělesná výkonnost MeSH
• zkracování telomer genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• práce podpořená grantem MeSH

Recombinant interferon-α (IFN-α) treatment functionally cures chronic hepatitis B virus (HBV) infection in some individuals and suppresses virus replication in hepatocytes infected in vitro. We studied the antiviral effect of conditioned media (CM) from peripheral blood mononuclear cells (PBMCs) stimulated with agonists of Toll-like receptors (TLRs) 2, 7, 8 and 9. We found that CM from PBMCs stimulated with dual-acting TLR7/8 (R848) and TLR2/7 (CL413) agonists were more potent drivers of inhibition of HBe and HBs antigen secretion from HBV-infected primary human hepatocytes (PHH) than CM from PBMCs stimulated with single-acting TLR7 (CL264) or TLR9 (CpG-B) agonists. Inhibition of HBV in PHH did not correlate with the quantity of PBMC-produced IFN-α, but it was a complex function of multiple secreted cytokines. More importantly, we found that the CM that efficiently inhibited HBV production in freshly isolated PHH via various cytokine repertoires and mechanisms did not reduce covalently closed circular (ccc)DNA levels. We confirmed our data with a cell culture model based on HepG2-NTCP cells and the plasmacytoid dendritic cell line GEN2.2. Collectively, our data show the importance of dual-acting TLR agonists inducing broad cytokine repertoires. The development of poly-specific TLR agonists provides novel opportunities towards functional HBV cure.

• MeSH
• buňky Hep G2 MeSH
• chronická hepatitida B virologie   MeSH
• cytokiny metabolismus   MeSH
• hepatocyty virologie   MeSH
• interferon alfa metabolismus   MeSH
• kruhová DNA metabolismus   MeSH
• kultivační média speciální farmakologie   MeSH
• lékové transportní systémy MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• přirozená imunita účinky léků   MeSH
• replikace viru účinky léků   MeSH
• toll-like receptory agonisté   metabolismus   MeSH
• virus hepatitidy B fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• buněčné jádro metabolismus   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• polymerázová řetězová reakce MeSH
• receptory kyseliny retinové genetika   klasifikace   metabolismus   MeSH
• Check Tag
• lidé MeSH

Aim: Development of type 2 diabetes (T2DM) is associated with disturbances in immune and metabolic status that may be reflected by an altered gene expression profile of peripheral blood mononuclear cells (PBMC). To reveal a potential family predisposition to these alterations, we investigated the regulation of gene expression profiles in circulating CD14+ and CD14- PBMC in fasting conditions and in response to oral glucose tolerance test (OGTT) in glucose tolerant first-degree relatives (FDR) of T2DM patients and in control subjects. Materials and Methods: This work is based on the clinical study LIMEX (NCT03155412). Non-obese 12 non-diabetic (FDR), and 12 control men without family history of diabetes matched for age and BMI underwent OGTT. Blood samples taken before and at the end of OGTT were used for isolation of circulating CD14+ and CD14- PBMC. In these cells, mRNA levels of 94 genes related to lipid and carbohydrate metabolism, immunity, and inflammation were assessed by qPCR. Results: Irrespectively of the group, the majority of analyzed genes had different mRNA expression in CD14+ PBMC compared to CD14- PBMC in the basal (fasting) condition. Seven genes (IRS1, TLR2, TNFα in CD14+ PBMC; ABCA1, ACOX1, ATGL, IL6 in CD14- PBMC) had different expression in control vs. FDR groups. OGTT regulated mRNA levels of nine genes selectively in CD14+ PBMC and of two genes (ABCA1, PFKL) selectively in CD14-PBMC. Differences in OGTT-induced response between FDR and controls were observed for EGR2, CCL2 in CD14+ PBMC and for ABCA1, ACOX1, DGAT2, MLCYD, and PTGS2 in CD14- PBMC. Conclusion: This study revealed a different impact of glucose challenge on gene expression in CD14+ when compared with CD14- PBMC fractions and suggested possible impact of family predisposition to T2DM on basal and OGTT-induced gene expression in these PBMC fractions. Future studies on these putative alterations of inflammation and lipid metabolism in fractionated PBMC in larger groups of subjects are warranted.

• MeSH
• biologické markery metabolismus   MeSH
• diabetes mellitus 2. typu genetika   metabolismus   patologie   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• glukózový toleranční test MeSH
• krevní glukóza analýza   MeSH
• leukocyty mononukleární metabolismus   patologie   MeSH
• lidé MeSH
• lipopolysacharidové receptory metabolismus   MeSH
• regulace genové exprese * MeSH
• studie případů a kontrol MeSH
• transkriptom * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• antigeny povrchové MeSH
• interferony MeSH
• leukocyty mononukleární MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie

Type 1 Diabetes (T1D) is considered to be a T-helper- (Th-) 1 autoimmune disease; however, T1D pathogenesis likely involves many factors, and sufficient tools for autoreactive T cell detection for the study of this disease are currently lacking. In this study, using gene expression microarrays, we analysed the effect of diabetes-associated autoantigens on peripheral blood mononuclear cells (PBMCs) with the purpose of identifying (pre)diabetes-associated cell processes. Twelve patients with recent onset T1D, 18 first-degree relatives of the TD1 patients (DRL; 9/18 autoantibody positive), and 13 healthy controls (DV) were tested. PBMCs from these individuals were stimulated with a cocktail of diabetes-associated autoantigens (proinsulin, IA-2, and GAD65-derived peptides). After 72 hours, gene expression was evaluated by high-density gene microarray. The greatest number of functional differences was observed between relatives and controls (69 pathways), from which 15% of the pathways belonged to "immune response-related" processes. In the T1D versus controls comparison, more pathways (24%) were classified as "immune response-related." Important pathways that were identified using data from the T1D versus controls comparison were pathways involving antigen presentation by MHCII, the activation of Th17 and Th22 responses, and cytoskeleton rearrangement-related processes. Genes involved in Th17 and TGF-beta cascades may represent novel, promising (pre)diabetes biomarkers.

• MeSH
• autoantigeny imunologie   metabolismus   MeSH
• autoprotilátky imunologie   metabolismus   MeSH
• diabetes mellitus 1. typu genetika   imunologie   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• exprese genu MeSH
• leukocyty mononukleární imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• prediabetes genetika   imunologie   metabolismus   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• elektronová mikroskopie MeSH
• gramnegativní bakterie fyziologie   MeSH
• leukocyty mononukleární fyziologie   MeSH
• Staphylococcus aureus fyziologie   MeSH