Jiranan Chotitumnavee achieved her Doctor of Pharmacy degree from the Faculty of Pharmaceutical Science, Khon Kaen University, Thailand in 2016. In that time, she had an opportunity to be a research internship at National Synchrotron Radiation Research Center in Hsinchu, Taiwan for three months operating a project at IR beamline end-station. After graduation, she worked as a teacher assistant at Mahidol University, Thailand. Then, she got a scholarship to be a research student, and currently, she is the first-year PhD student in the graduate school of medical science, Kyoto Prefectural University of Medicine.
Histone lysine demethylases (KDMs) play an essential role in the demethylation process of histone lysine residues by the oxidative mechanism. Two families of histone lysine demethylases have been identified based on their structure and catalytic reaction, which are flavin-dependent lysine demethylases and Jumonji C-containing (JmjC) lysine demethylases. The JmjC lysine demethylases are Fe(II)/α-ketoglutarate (αKG)-dependent oxygenases. KDM5A, an isoform of the JmjC lysine demethylases was chosen as a target KDM in this work. KDM5A plays a pivotal role in removing the di-and tri-methylation mark of lysine 4 on histone 3 (H3K4). KDM5A is overexpressed in several human cancer cells including lung, gastric, breast, and liver cancers. KDM5A has been reported to be involved in tumor formation, metastasis and advance of drug resistance in human cancers, suggesting KDM5A as a potential target for cancer treatment. In this study, we designed αKG analogues as JmjC lysine demethylase inhibitors since αKG acts as a crucial cofactor of these enzymes. The inhibitory activity of the αKG analogues was evaluated by an AlphaScreen KDM5A enzymatic assay, and western blotting analysis was performed to examine the methylation level change of H3K4 in A549 lung cancer cell lines. The results of the enzymatic assay and western blotting analysis showed that an αKG analogue inhibited KDM5A activity significantly and its ester prodrug enhanced the methylation of H3K4 in a dose-dependent manner in A549 lung cancer cell lines. Thus, the αKG analogue is a promising lead for KDM5A inhibitors.
Fadwa M Al-Sharif has completed her PhD from the Medical School of Manchester. She was the Director of Medical Technology Department. She has published more than 25 papers in reputed journals. She has been involved in different committee in the faculty such as, Academic Affairs Committee, PhD Program Committee and Academic Accreditation Committee.
Introduction: Currently, the global prevalence of asthma and obesity is progressively rising. However, obesity is linked with systemic inflammation and altered immune system parameters. There is limited studies investigated the immuno-competence among asthmatic obese patients. Objective: This study is designed to detect the association between immune system response, inflammatory cytokines and body mass index among asthmatic Saudi patients. Subjects & Method: One hundred (100) asthmatic obese Saudi patients of both sexes; their age mean was 42.63±9.15 year and their Body Mass Index (BMI) mean was 32.42±2.96 Kg/m2 known as group A, in addition to 100 non-obese asthmatic, who were gender, age and BMI matched with study group, were enrolled in the study. Result: There was higher levels of high-sensitivity C-Reactive Protein (hsCRP), Interleukin-6 (IL-6), Tumor Necrotic Factoralpha (TNF-α), serum IgE, white blood cells count, total leukocytes count, neutrophils count, monocytes, lymphocytes count, T-lymphocytes (CD3) count and B lymphocytes (CD19) count among obese asthmatics (group A) than lean asthmatic (group B), in addition to a strong association between these parameters and body mass index in both groups. Conclusion: There is a strong association between inflammatory cytokines, immune system response and BMI among obese asthmatic patients; therefore future studies are essential to explore impact of life style modification intervention on immune system and systemic inflammation modulation.