The aim of the present study was to assess whether BAY 11-7082, a nuclear factor-kappaB (NF-κB) inhibitor, influences the level of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), and NF-κB related signaling pathways in the liver. The animals were divided into 4 groups: I: saline; II: saline + endothelin-1 (ET-1) (1.25 μg/kg b.w., i.v.); III: saline + ET-1 (12.5 μg/kg b.w., i.v.); and IV: BAY 11-7082 (10 mg/kg b.w., i.v.) + ET-1 (12.5 μg/kg b.w., i.v.). Injection of ET-1 alone at a dose of 12.5 μg/kg b.w. showed a significant (P < 0.001) increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) level and decrease (P < 0.01) in GSH level (vs. control). ET-1 administration slightly downregulated gene expression of p65 of NF-κB but potently and in a dose-dependent way downregulated p21-cip gene expression in the liver. BAY 11-7082 significantly decreased TBARS (P < 0.001), H2O2 (P < 0.01) and improved the redox status (P < 0.05), compared to ET-1 group. The concentration of TNF-α was increased in the presence of ET-1 (P < 0.05), while BAY 11-7082 decreased TNF-α concentration (P < 0.01). Inhibition of IkBα before ET-1 administration downregulated gene expression of p21-cip but had no effect on p65.

Background: Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier.Methods: C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).Results: The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers.Conclusions: This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents.

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Abstract. The aim of the present study was to evaluate the mRNA expression level of the runt-related transcription factor 1 (RUNX1) and runt-related transcription factor 3 (RUNX3) genes in patients with acute myeloid leukemia (AML). The etiology of AML is not yet fully known, but certain genetic factors may contribute to its manifestation. The RUNX1 and RUNX3 genes have been demonstrated to serve a role in the transcription process. The group investigated in the present study included 43 patients diagnosed with AML, and the relative RUNX1 and RUNX3 expression levels were determined using reverse transcription-quantitative polymerase chain reaction. The results indicated that RUNX1 and RUNX3 expression was associated with clinicopathological features, including sex and mortality risk. Expression levels of the RUNX1 gene were higher and more variable among females (P=0.044), and mortality was more frequent among patients with a higher RUNX3 expression level (P=0.036). The data obtained from the present study suggested that RUNX3 expression may have potential value as a prognostic factor; furthermore, sex is potentially a factor that may affect the difference in RUNX1 gene expression level among females and males. Further analyses in this field will aid in the identification and elucidation of the molecular basis of leukemia.

The promoter, 5' UTR, and 34-nt 5' fragments of protein encoding region of the Salvia miltiorrhiza copalyl diphosphate synthase gene were cloned and characterized. No tandem repeats, miRNA binding sites, or CpNpG islands were observed in the promoter, 5' UTR, or protein encoding fragments. The entire isolated promoter and 5' UTR is 2235 bp long and contains repetitions of many cis-active elements, recognized by homologous transcription factors, found in Arabidopsis thaliana and other plant species. A pyrimidine-rich fragment with only 6 non-pyrimidine bases was localized in the 33-nt stretch from nt 2185 to 2217 in the 5' UTR. The observed cis-active sequences are potential binding sites for trans-factors that could regulate spatio-temporal CPS gene expression in response to biotic and abiotic stress conditions. Obtained results are initially verified by in silico and co-expression studies based on A. thaliana microarray data.The quantitative RT-PCR analysis confirmed that the entire 2269-bp copalyl diphosphate synthase gene fragment has the promoter activity.Quantitative RT-PCR analysis was used to study changes in CPS promoter activity occurring in response to the application of four selected biotic and abiotic regulatory factors; auxin, gibberellin, salicylic acid, and high-salt concentration.