DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy.

Protein and DNA methylation is involved in various biological functions such as signal transmission, DNA repair, and gene expression. Abnormal regulation of methyltransferases has been linked to multiple types of cancer, but its link to autophagy and carcinogenesis in breast and lung cancer is not fully understood. We utilized UALCAN, a web tool, to investigate breast and lung cancer database from The Cancer Genome Atlas. We found that 17 methyltransferases are upregulated in breast and/or lung cancer. We investigated the effect of methylation inhibition on two breast cancer cell lines (MDA-MB-231 and MCF-7) and two lung cancer cell lines (H292 and A549) by treating them with the indirect methyltransferase inhibitor adenosine dialdehyde (AdOx). We found that the migration ability of all cell lines was decreased, and the growth rate of MDA-MB-231, MCF-7 and H292 was also decreased after AdOx treatment. These results were correlated with an inhibition of the autophagy in MDA-MB-231, MCF-7 and H292 cell lines, since AdOx treatment induced a decreased expression of ATG7, a reduced ratio LC3-II/LC3-I and an increased p62 level. These findings suggest that inhibiting cells' methylation ability could be a potential target for breast and lung cancer treatment.

Molecular Modelling Study and Antibacterial Evaluation of Diphenylmethane Derivatives as Potential FabI Inhibitors.

The need for new antibiotics has become a major worldwide challenge as bacterial strains keep developing resistance to the existing drugs at an alarming rate. Enoyl-acyl carrier protein reductases (FabI) play a crucial role in lipids and fatty acid biosynthesis, which are essential for the integrity of the bacterial cell membrane. Our study aimed to discover small FabI inhibitors in continuation to our previously found hit MN02. The process was initially started by conducting a similarity search to the NCI ligand database using MN02 as a query. Accordingly, ten compounds were chosen for the computational assessment and antimicrobial testing. Most of the compounds showed an antibacterial activity against Gram-positive strains, while RK10 exhibited broad-spectrum activity against both Gram-positive and Gram-negative bacteria. All tested compounds were then docked into the saFabI active site followed by 100 ns MD simulations (Molecular Dynamics) and MM-GBSA (Molecular Mechanics with Generalised Born and Surface Area Solvation) calculations in order to understand their fitting and estimate their binding energies. Interestingly, and in line with the experimental data, RK10 was able to exhibit the best fitting with the target catalytic pocket. To sum up, RK10 is a small compound with leadlike characteristics that can indeed act as a promising candidate for the future development of broad-spectrum antibacterial agents.

Association between visual impairment and sleep duration in college students: A study conducted in UAE and Lebanon.

Objective: To examine whether self-reported sleep duration and visual impairment were associated among College students. Participants: Students (n = 1002, age 17-35 years) from Lebanon and the United Arab Emirates. Methods: Students were asked to complete a validated questionnaire between October 2018 and May 2019. The questions were related to sociodemographics, lifestyle characteristics, visual impairment status, sleeping pattern, mobile-phone use and chronic conditions. Results: 18.3% of the respondents reported to suffer from visual impairment. Among them, 72.7% were females (p < .001), 65% admitted to frequently use mobile phones before sleeping (p < .001), 54.6% reported to sleep less than 7 h (p = .008) and 71.6% reported to suffer from sleep disturbances (p = .05). Visual impairment was associated with poor sleep quality (p < .001), mobile phone use before sleeping (p < .01) and daily stress (p < .05). Conclusion: Visual impairment in college students is associated with short sleep duration, mobile phone use before sleeping and stress level.

Expired medications and disposal practices in Arab households.

OBJECTIVES: Over the past few decades, the accumulation of expired and unused medications in households has become a concern. Most people are unaware of how to properly dispose of unused and/or expired medicines. Our objective was to inspect the extent of expired medications within Arab households in United Arab Emirates (UAE), to determine which therapeutic groups yield greater amounts of unused medications, and evaluate drugs' disposal practices. METHODS: This descriptive study was written in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies. It was conducted among Arab households in UAE (n = 503) using an online questionnaire between November 2020 and January 2021. Questions were related to participants' socio-demographics, the prevalence of expired medications in households and their disposal. KEY FINDINGS: Around 58% of the respondents had expired medications in their houses and 74% had drugs that were never used. The most common medicines left unused were analgesics (34%) followed by cosmetics (27%) and antibiotics (26%). More than 42% of expired medications were in solid dosage forms, 28% were semisolid and 24% were liquid dosage forms. The predominant disposal method among the surveyed participants was throwing medications into the garbage (86%). CONCLUSIONS: Large quantities of expired medications in Arab households exist with a high prevalence of analgesics, antibiotics and cosmetics. Arab households are unaware of the proper drug disposal procedures. Therefore, community pharmacists are recommended to offer training on proper medication disposal practices and to encourage the public to return medications to pharmacies.

The patterns and determinants of telemedicine use during the COVID-19 crisis: A nationwide study.

BACKGROUND: Although telemedicine services have been adopted on a large scale in the United Arab Emirates (UAE) during the coronavirus disease 2019 (COVID-19) pandemic, a little is known about the public experience. OBJECTIVES: This study aimed to investigate consumers' patterns, nature, and predictors of telemedicine utilization and consumers' attitude toward this technology. METHODS: A quantitative, self-administered questionnaire was developed, validated, and delivered randomly to adults living across the United Arab Emirates (UAE) between January 2021 and January 2022. The questionnaire included questions about categories of telemedicine used, purpose of use, challenges encountered during the use of telemedicine, and reasons for not using telemedicine technology. We adopted a proportionate random sampling technique to recruit participants by 3 ways: social media, phone calls, and face to face. RESULTS: The final dataset included 1584 participants, of which 496 (31.3%) used telemedicine during the coronavirus disease 2019 (COVID-19) pandemic. The most common reasons for not using telemedicine during COVID-19 was having no idea that telemedicine exists (38.3%, 417 of 1088) or having no idea how to use it (33.5%, 365 of 1088). Telemedicine users reported that that telepharmacy (89.7%), teleconsultation (78.2%), and telediagnosis (23.0%) were the most frequently used telemedicine services during the COVID-19 crisis. Of the 496 telemedicine users, 469 (94.6%) reported using telemedicine for seeking a pharmacist advice about medication instructions, 422 (85.1%) for ordering nonprescription drugs, and 401 (80.8%) for seeking a physician advice. Those with high activity on social media were less likely to be associated with telemedicine users versus nonusers. DISCUSSION: Although telepharmacy has been increasingly used by consumers, more attention is needed to fix its limitations and improve patient safety. CONCLUSION: This study shows a positive attitude and a general acceptance of telemedicine services among the UAE population. Some sociodemographic and clinical characteristics were significantly associated with the use of telemedicine during the pandemic.

The Discovery of Potent SHP2 Inhibitors with Anti-Proliferative Activity in Breast Cancer Cell Lines.

Despite available treatments, breast cancer is the leading cause of cancer-related death. Knowing that the tyrosine phosphatase SHP2 is a regulator in tumorigenesis, developing inhibitors of SHP2 in breast cells is crucial. Our study investigated the effects of new compounds, purchased from NSC, on the phosphatase activity of SHP2 and the modulation of breast cancer cell lines' proliferation and viability. A combined ligand-based and structure-based virtual screening protocol was validated, then performed, against SHP2 active site. Top ranked compounds were tested via SHP2 enzymatic assay, followed by measuring IC50 values. Subsequently, hits were tested for their anti-breast cancer viability and proliferative activity. Our experiments identified three compounds 13030, 24198, and 57774 as SHP2 inhibitors, with IC50 values in micromolar levels and considerable selectivity over the analogous enzyme SHP1. Long MD simulations of 500 ns showed a very promising binding mode in the SHP2 catalytic pocket. Furthermore, these compounds significantly reduced MCF-7 breast cancer cells' proliferation and viability. Interestingly, two of our hits can have acridine or phenoxazine cyclic system known to intercalate in ds DNA. Therefore, our novel approach led to the discovery of SHP2 inhibitors, which could act as a starting point in the future for clinically useful anticancer agents.