Ameliorative inhibition of sirtuin 6 by imidazole derivative triggers oxidative stress-mediated apoptosis associated with Nrf2/Keap1 signaling in non-small cell lung cancer cell lines.

Background: Redox homeostasis is the vital regulatory system with respect to antioxidative response and detoxification. The imbalance of redox homeostasis causes oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis. Nrf2/Keap1 signaling is reported to be involved in cancer cell growth and survival. A high level of Nrf2 in cancers is associated with poor prognosis, resistance to therapeutics, and rapid proliferation, framing Nrf2 as an interesting target in cancer biology. Sirtuins (SIRT1-7) are class III histone deacetylases with NAD + dependent deacetylase activity that have a remarkable impact on antioxidant and redox signaling (ARS) linked with Nrf2 deacetylation thereby increasing its transcription by epigenetic modifications which has been identified as a crucial event in cancer progression under the influence of oxidative stress in various transformed cells. SIRT6 plays an important role in the cytoprotective effect of multiple diseases, including cancer. This study aimed to inhibit SIRT6 using an imidazole derivative, Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate, to assess its impact on Nrf2/Keap1 signaling in A549 and NCI-H460 cell lines. Method: Half maximal inhibitory concentration (IC50) of Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate was fixed by cell viability assay. The changes in the gene expression of important regulators involved in this study were examined using quantitative real-time PCR (qRT-PCR) and protein expression changes were confirmed by Western blotting. The changes in the antioxidant molecules are determined by biochemical assays. Further, morphological studies were performed to observe the generation of reactive oxygen species, mitochondrial damage, and apoptosis. Results: We inhibited SIRT6 using Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate and demonstrated that SIRT6 inhibition impacts the modulation of antioxidant and redox signaling. The level of antioxidant enzymes and percentage of reactive oxygen species scavenging activity were depleted. The morphological studies showed ROS generation, mitochondrial damage, nuclear damage, and apoptosis. The molecular examination of apoptotic factors confirmed apoptotic cell death. Further, molecular studies confirmed the changes in Nrf2 and Keap1 expression during SIRT6 inhibition. Conclusion: The overall study suggests that SIRT6 inhibition by imidazole derivative disrupts Nrf2/Keap1 signaling leading to oxidative stress and apoptosis induction.

Visual status among undergraduate students: Findings from an emerging university in Saudi Arabia.

BACKGROUND: Refractive error is an important preventable cause of visual impairment and blindness worldwide. In adult life, reduced vision can potentially affect the academic performance, choice of occupation and socio-economic status. This study aimed to assess the prevalence of refractive errors and related visual impairment among undergraduate male students in Prince Sattam bin Abdulaziz University in Al-Kharj, Saudi Arabia. METHODS: A descriptive cross-sectional study was employed in the current work. After obtaining an informed consent; each eligible student was asked to fill a self-constructed survey and have screened in the college premises for visual acuity and refractive error. Candidates detected with defective vision have been referred for further examination at well-equipped ophthalmology clinic in the University Hospital. RESULTS: A total of 420 undergraduate students, with age ranged from 18 to 30 years, have participated in the current study. About 25.0% of the participants have used spectacles at the time of examination. Positive family history of spectacles use was found in 71.4%. Our study showed that visual acuity in the better eye was low in 34.76% of the participants. Seventy-eight students (18.6%) of the total participants reported defective vision and have fulfilled refractometric examination. Of the examined students 83.3% were found to have refractive errors. Astigmatism, 52.6%, was the most frequently encountered refractive error among the participants; followed by myopia, 26.9%; and hypermetropia 2.6%. CONCLUSION: The current study confirms that refractive error is an important preventable cause of visual impairment. Significant portion of the examined participants were found to have refractive errors recommending further work to improve visual status in undergraduate students.

Awareness among the general population about lipid profile screening in individuals over 20 years old in Alriyadh, Saudi Arabia.

INTRODUCTION: Plasma cholesterol and triglycerides are clinically important because their abnormally high levels are major treatable risk factors for cardiovascular disease. This study aimed to evaluate the awareness, general knowledge, and attitudes about regular lipid profile screening among adult individuals in Al-Riyadh. MATERIAL AND METHODS: This is a cross-sectional study collected by convenience sampling method. Residents of Riyadh region older than 20 years were targeted through an electronic questionnaire distributed via Twitter and WhatsApp. The study was conducted between November 28, 2016 and December 31, 2016. Study results were analysed using the SPSS system. RESULTS: This study included 1383 participants; 646 (46.7%) were male and 737 (53.3%) female. Of them, 905 (65.4%) did not screen for their lipid profiles, while 478 (34.6%) screened. A visit to a primary health care facility or hospital was the reason for screening of lipid profile in 195 (14.1%) of the participants, whereas 64 (4.6%) of them were ordered by doctors. CONCLUSIONS: More educated participants were found to be more aware of the importance of screening lipid profile. Our results reflect poor awareness among the population regarding the importance of regular screening of lipid profiles. A visit to primary health care or hospital was the most frequent reason for screening of lipid profile. Screening lipid profiles was predominant among males and it was significantly related to the gender, age, and educational level. This shows the strong need in the community for health education about the importance of screening lipid profile at different levels of health care delivery.