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Jan Vondrácek Miroslav Machala Vítezslav Bryja Katerina Chramostová Pavel Krcmár Cornelia Dietrich Ales Hampl Alois Kozubík 《Toxicological sciences》2005,83(1):53-63
Polychlorinated biphenyls (PCBs) exhibit tumor-promoting effects in experimental animals. We investigated effects of six model PCB congeners and hydroxylated PCB metabolites on proliferation of contact-inhibited rat liver epithelial WB-F344 cells. The 'dioxin-like' PCB congeners, PCB 126, PCB 105, and 4'-OH-PCB 79, a metabolite of the planar PCB 77 congener, induced cell proliferation in a concentration-dependent manner. In contrast, the 'non-dioxin-like' compounds that are not aryl hydrocarbon receptor (AhR) agonists, PCB 47, PCB 153, and 4-OH-PCB 187, an abundant noncoplanar PCB metabolite, had no effect on cell proliferation at concentrations up to 10 muM. The concentrations of dioxin-like PCBs leading to cell proliferation corresponded with the levels inducing the expression of cytochrome P450 1A1 mRNA, suggesting that the release from contact inhibition was associated with AhR activation. The effects of PCB 126 and PCB 153 on expression of proteins controlling G0/G1-S-phase transition and S-phase progression were compared. Only PCB 126 was found to upregulate cyclin A and D2 protein levels, and to increase both total cyclin-dependent kinase 2 (cdk2) and cyclin A/cdk2 complex activities. Despite the observed upregulation of cyclin D2, no increase in cdk4 activity was observed. The expression of cdk inhibitor p27Kip1 was not affected by either PCB 126 or PCB 153. These results suggest that dioxin-like PCBs can induce cell proliferation of contact-inhibited rat liver epithelial cells by increasing cyclin A protein levels, a process that then leads to upregulation of cyclin A/cdk2 activity and initiation of DNA replication. This mechanism could be involved in tumor-promoting effects of dioxin-like PCBs. 相似文献
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Prospective study of signalling pathways in myeloma bone disease with regard to activity of the disease,extent of skeletal involvement and correlation to bone turnover markers
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Ivona Markelić Iva Hlapčić Dunja Rogić Ivana Rako Miroslav Samaržija Sanja Popović-Grle Lada Rumora Andrea Vukić Dugac 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2021,31(1):153-161
Background and aimsLimited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy.Methods and resultsThe study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated.HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742–0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases.ConclusionLipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia. 相似文献
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Lenka Sedlarikova Barbora Gromesova Veronika Kubaczkova Lenka Radova Jana Filipova Jiri Jarkovsky Lucie Brozova Roberta Velichova Martina Almasi Miroslav Penka Renata Bezdekova Martin Stork Zdenek Adam Ludek Pour Marta Krejci Petr Kuglík Roman Hajek Sabina Sevcikova 《European journal of haematology》2017,99(3):223-233
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Prucha Miroslav Zazula Roman Russwurm Stefan 《Archivum immunologiae et therapiae experimentalis》2017,65(1):37-49
Archivum Immunologiae et Therapiae Experimentalis - Sepsis is the most frequent cause of death in noncoronary intensive care units. In the past 10 years, progress has been made in the... 相似文献