Ecem Fatma Karaman

Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery

Abstract Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p < 0.05). Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin

Telomerase Reverse Transcriptase (TERT) Gene Variations and Susceptibility of Colorectal Cancer

AIMnColorectal cancer is the third most common cause of cancer-related mortality. Previous studies demonstrated increased telomerase activity in colorectal cancer tissue and suggested a prognostic value for patients with colorectal carcinoma. Telomerase reverse transcriptase (TERT), one of the main functional subunits of the telomerase, is an important factor in modulating telomerase activity, telomere length, and genomic stability. However, there are few studies that have addressed the association between genetic variation at TERT and the risk of colorectal cancer.nnnMETHODnWe evaluated the influence of three common single-nucleotide polymorphisms (SNPs) of the TERT gene (rs2853669, rs2736100, rs2736098) on susceptibility to colorectal cancer in 104 patients and 135 controls in a Turkish population.nnnRESULTSnWe observed that rs2736098 was significantly associated with increased risk of colorectal cancer (ORu2009=u20092.53; 95% CIu2009=u20091.26-5.10; pu2009=u20090.008). On the other hand, rs2736100 and rs2853669 showed no association with colorectal cancer (p ≥ 0.128).nnnCONCLUSIONnThese findings are the first results of TERT allele distributions in the Turkish population and also provide increased understanding with respect to colorectal cancer etiology.

Effects of BPA on global DNA methylation and global histone 3 lysine modifications in SH-SY5Y cells: An epigenetic mechanism linking the regulation of chromatin modifiying genes

Bisphenol A (BPA), an estrogenic endocrine disruptor, is widely used in the production of polycarbonate plastic and epoxy resins, resulting in high risk on human health. In present study we aimed to investigate the effects of BPA on global and gene specific DNA methylation, global histone modifications and regulation of chromatin modifiying enzymes in human neuroblastoma cells (SH-SY5Y). Cells were treated with BPA at 0.1, 1 and 10μM concentrations for 48 and 96h. IC50 value of BPA was determined as 183 and 129μM in SH-SY5Y cells after 24h by MTT and NRU tests, respectively. We observed significant alterations on the 5-mC% levels (1.3 fold) and 5-hmC% levels (1.67 fold) after 10μM of BPA for 96h. Significant decrease was identified in H3K9me3 and H3K9ac after 10μM of BPA for 96h while decrease was observed in H3K4me3 at 10μM of BPA for 48h. Alterations were observed in chromatin modifiying genes including G9a, EZH2, SETD8, SETD1A, HAT1, SIRT1, DNMT1, RIZ1 and Suv39h1 after 96h of BPA exposure. Taken together, this study suggests that BPA might modulate the epigenetic regulators which would be key molecular events in the toxicity of endocrine disrupting chemicals.