Endometrial cancer develops as a result of abnormal cell growth associated with uncontrolled cell proliferation, excessive activation of signaling pathways and miRNA activity. The aim of this study was to determine the expression profile of genes associated with cell proliferation and to assess which miRNAs can participate in the regulation of their expression. The study enrolled 40 patients with endometrial cancer and 10 patients without neoplastic changes. The expression profile of genes associated with cell proliferation and the expression profile of miRNAs were assessed using microarrays. RT-qPCR was performed to validate mRNA microarray results. The mirTAR tool was used to identify miRNAs that regulate the activity of genes associated with cell proliferation. Decreased expression of IGF1 and MYLK, as well as SOD2 overexpression, were observed in endometrial cancer using both mRNA microarrays and RT-qPCR. Microarray analysis showed low levels of NES and PRKCA, but this was only partially validated using RT-qPCR. Reduced activity of MYLK may be caused by increased miR-200c, miR-155 and miR-200b expression. Cell proliferation is disturbed in endometrial cancer, which may be associated with an overexpression of miR-200a, miR-200c, and miR-155, making it a potential diagnostic marker.
Nowadays, antibiotic resistance is a major public health problem. Among staphylococci, infections caused by Staphylococcus epidermidis (S. epidermidis) are frequent and difficult to eradicate. This is due to its ability to form biofilm. Among the antibiotic substances, nanosilver is of particular interest. Based on this information, we decided to investigate the effect of nanosilver on the viability, biofilm formation and gene expression of the icaADBC operon and the icaR gene for biofilm and non-biofilm S. epidermidis strains. As we observed, the viability of all the tested strains decreased with the use of nanosilver at a concentration of 5 µg/mL. The ability to form biofilm also decreased with the use of nanosilver at a concentration of 3 µg/mL. Genetic expression of the icaADBC operon and the icaR gene varied depending on the ability of the strain to form biofilm. Low concentrations of nanosilver may cause increased biofilm production, however no such effect was observed with high concentrations. This confirms that the use of nanoparticles at an appropriately high dose in any future therapy is of utmost importance. Data from our publication confirm the antibacterial and antibiotic properties of nanosilver. This effect was observed phenotypically and also by levels of gene expression.
Antiretroviral restriction factors may play an essential role in the safety of xenotransplantation. Therefore, the present study focused on investigation of the changes in the tripartite motif-containing family ( TRIM ) gene expression in normal human dermal fibroblasts with and without lipopolysaccharide stimulation in response to porcine endogenous retrovirus infection. Analysis of the expression profile of TRIMs was performed using oligonucleotide microarrays and QRT-PCR. Nine ( TRIM1 , TRIM2 , TRIM5 , TRIM14 , TRIM16 , TRIM18 , TRIM22 , TRIM27 and TRIM31 ) statistically significantly differentially expressed genes were found (P < 0.05, one-way ANOVA). In conclusion, comprehensive analysis of retroviral restriction factor gene expression in human dermal fibroblasts before and after porcine endogenous retrovirus infection with and without LPS stimulation may suggest association of the selected TRIMs with antiretroviral activity.
Betulin and its derivatives, 28-propyne derivative EB5 and 29-diethyl phosphonate analog ECH147, are promising compounds in anti-tumor activity studies. However, their effect on kidney cells has not yet been studied. The study aimed to determine whether betulin and its derivatives—EB5 and ECH147—influence the viability and oxidative status of human renal proximal tubule epithelial cells (RPTECs). The total antioxidant capacity of cells (TEAC), lipid peroxidation product malondialdehyde (MDA) level, and activity of antioxidant enzymes (SOD, CAT, and GPX) were evaluated. Additionally, the mRNA level of genes encoding antioxidant enzymes was assessed. Cisplatin and 5-fluorouracil were used as reference substances. Betulin and its derivatives affected the viability and antioxidant systems of RPTECs. Betulin strongly reduced TEAC in a concentration-dependent manner. All tested compounds caused an increase in MDA levels. The activity of SOD, CAT, and GPX, and the mRNA profiles of genes encoding antioxidant enzymes depended on the tested compound and its concentration. Betulin showed an cisplatin-like effect, indicating its nephrotoxic potential. Betulin derivatives EB5 and ECH147 showed different impacts on the antioxidant system, which gives hope that these compounds will not cause severe consequences for the kidneys in vivo.
1 October 2018 in Current Pharmaceutical Biotechnology
The aim of this study was to evaluate the influence of adalimumab on the expression pattern of genes associated with JAK/STAT signaling pathway in Normal Human Dermal Fibroblast (NHDF) cells stimulated with 8 µg/ml of adalimumab and the identification of miRNAs regulating these genes' expression. NHDFs were cultured with or without the presence of adalimumab for 2, 8, and 24h. The microarray technology was used to determine expression profile of mRNAs and miRNAs. Out of 22283 ID mRNA, 37 are associated with the JAK/STAT signaling pathway. It can be observed that 18 mRNAs differentiate NHDFs cultures with adalimumab from control. The analysis of miRNAs showed that, among 1105 ID miRNAs, 20 miRNAs are differentiating in cells treated with adalimumab for 2h, 9 miRNAs after 8h, and only 3 miRNAs after 24h. It can be observed that miRNAs play an extremely important role in the regulation of the expression of genes associated with JAK/STAT signaling pathway. The results of this study show the possibility of using changes in mRNAs and miRNAs profile expression, as complementary molecular markers of adalimumab treatment effectiveness.