The epidermis is a stratified epithelium that protects the organism against environmental insults. The maintenance of the epidermis is provided by sustained proliferation and differentiation of the keratinocyte stem cells localized to the basal layer of the epidermis (Fuchs and Nowak, 2008; Blanpain and Fuchs, 2009). As keratinocyte stem cells commit to differentiate, they cease to proliferate and start to move upward to form suprabasal layers, including spinous, granular, and stratum corneum with different biochemical contents and morphologies (Fuchs and Nowak, 2008). In this differentiation process, transcription factor p63, which is the well-known master regulator of keratinocyte differentiation, regulates the expression of a plethora of proteins involved in keratinocyte differentiation and maintenance, including receptor-interacting protein kinase 4 (RIPK4), interferon regulatory factor 6 (IRF6), inhibitory kappa B kinase α (IKKα), and keratin 14 (KRT14)

Colorectal cancer is one of the most common types of cancer. Drug resistance and drug-induced damage of healthy tissues are major obstacles in cancer treatment. Therefore, to develop efficient anticancer therapy, it is necessary to find compounds that affect tumor cells, but do not exhibit toxicity to healthy cells. Caffeic acid phenethyl ester (CAPE) has been demonstrated to have anticancer properties in many types of cancer. In this study, the cytotoxic and apoptotic effects of CAPE on the RKO colorectal cancer cell line and CCD 841-CoN normal colorectal cell line was investigated. In addition, changes in the survivin expression were determined. According to the results, CAPE decreased cell viability in the RKO cell line in a dose-dependent manner. Likewise, CAPE induced apoptotic cell death in approximately 40% of the RKO cells. Furthermore, CAPE treatment increased the Serine 15 (Ser15) and Serine 46 (Ser46) phosphorylation of p53, while decreased the survivin expression. The results suggested that CAPE induced apoptosis by regulating p53 phosphorylation, leading to inhibition of the survivin expression. In accordance with the results, it is suggested that CAPE might be evaluated as an alternative drug in cancer therapy and further investigation is needed within this scope.

OBJECTIVE: Various cytokine polymorphisms have been associated with genetic risk factors predisposing to Rheumatoid Arthritis (RA) in different populations. To predict the clinical outcome as well as response to therapy in RA, studies aimed to describe genetic markers. The present study aims to search for polymorphisms of 13 cytokine coding genes in the Eastern Black Sea Region of Turkey. METHODS: DNAs of 49 patients and 96 healthy bone marrow and kidney donors were isolated from peripheral blood samples. Genotyping was performed using the Heidelberg Cytokine Typing Tray kit. PCR products were visualized on an agarose gel, and results were analyzed using the interpretation scheme provided with the kit. Arlequin 3.5 software was used for statistical analysis. RESULTS: No positive association was found between allele frequencies and the disease. However, a negative association was found for the IL-A -889 C allele (p=0.02, OR=0.533, Wald’s 95% CI=0.318–0.893). IL-12 -1188 CC (p=0.01, OR=3.667, Wald’s 95% CI=1.246–10.786), IL-4 -1098 GT (p=0.02, OR=2.405, Wald’s 95% CI=1.129–5.125) genotypes were found positively associated with the RA, while IL-4 -590 CT (p=0.02, OR=0.422, Wald’s 95% CI=0.201–0.886) was found negatively associated with the disease. In addition, IL-6 GG haplotype was found positively associated with the RA (p=0.02, OR=1.880, Wald’s 95% CI=1.086–3.254). CONCLUSION: Our findings suggest that some polymorphisms of the IL-1A, IL-2, IL-4, IL-6 and IL-12 could be responsible for the susceptibility or protective to RA in our study population. Multi-centered and large numbers of subjects containing studies that search for cytokine polymorphisms will gather more information regarding the susceptibility to RA of Turkish patients.