Delivery of siRNA in vitro and in vivo using PEI-capped porous silicon nanoparticles to silence MRP1 and inhibit proliferation in glioblastoma.

BACKGROUND: Multidrug resistance-associated protein 1 (MRP1) overexpression plays a major role in chemoresistance in glioblastoma multiforme (GBM) contributing to its notorious deadly nature. Although MRP1-siRNA transfection to GBM in vitro has been shown to sensitise the cells to drug, MRP1 silencing in vivo and the phenotypic influence on the tumour and normal tissues upon MRP1 down-regulation have not been established. Here, porous silicon nanoparticles (pSiNPs) that enable high-capacity loading and delivery of siRNA are applied in vitro and in vivo. RESULT: We established pSiNPs with polyethyleneimine (PEI) capping that enables high-capacity loading of siRNA (92 µg of siRNA/mg PEI-pSiNPs), and optimised release profile (70% released between 24 and 48 h). These pSiNPs are biocompatible, and demonstrate cellular uptake and effective knockdown of MRP1 expression in GBM by 30%. Also, siRNA delivery was found to significantly reduce GBM proliferation as an associated effect. This effect is likely mediated by the attenuation of MRP1 transmembrane transport, followed by cell cycle arrest. MRP1 silencing in GBM tumour using MRP1-siRNA loaded pSiNPs was demonstrated in mice (82% reduction at the protein level 48 h post-injection), and it also produced antiproliferative effect in GBM by reducing the population of proliferative cells. These results indicate that in vitro observations are translatable in vivo. No histopathological signs of acute damage were observed in other MRP1-expressing organs despite collateral downregulations. CONCLUSIONS: This study proposes the potential of efficient MRP1-siRNA delivery by using PEI-capped pSiNPs in achieving a dual therapeutic role of directly attenuating the growth of GBM while sensitising residual tumour cells to the effects of chemotherapy post-resection.

The Incidence and Severity of COVID-19 Infection Post Vaccination in Saudi Arabia.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Presently, there is ongoing continuous research for more therapeutic options with a wide variety of vaccine availability. However, many people have worried about the vaccine's side effects. Hence, the current study was conducted to determine the prevalence of vaccinated individuals, side effects, and the rate of infectivity post vaccination including the three doses of vaccinations. Methods A cross-sectional questionnaire-based survey was conducted using Google Forms (Google, Inc., Mountain View, CA). Five hundred forty-three individuals participated and reported their status of COVID-19 infection, vaccination, and side effects. All the participants from Saudi Arabia received all the vaccine shots including the booster dose. Results Most of the Saudi nationals were fully vaccinated, and most received Pfizer vaccines for their first and second shots. Pain at the injection site was reported as the most common adverse effect followed by fever, headache, fatigue, and joint pain. Conclusion From the findings, it is concluded that most of the population of Saudi Arabia was vaccinated effectively. Pain at the injection site is identified as the primary adverse effect of vaccination. Most of the population is vaccinated with the Pfizer vaccine. Long-term side effect monitoring is recommended with large population studies to confirm the status of vaccines and adverse effects.

Factor XII deficiency in asymptomatic Saudi population: A retrospective cohort study.

Factor XII (FXII) deficiency is a rare genetic blood disorder. It can lead to a higher risk of developing deep vein thrombosis or acquired thrombotic disorders than the general population. This retrospective study evaluated patients who opted for surgery and were found to have abnormal clotting profiles and clotting factors on preoperative routine blood. Patients were included regardless of whether they were symptomatic or asymptomatic. The cohort comprised 115 patients with a mean FXII level of 128.04 ± 36.93%. Two (1.79%) patients, both of whom were women, had FXII levels <60%. The mean FXII level was 58 ± 1.41 (range, 57-59%) in this group. The present study shows the prevalence of FXII in the asymptomatic Saudi population. The results provide the normal range for FXII. The findings of our study provide the basis for diagnosing F XII deficiency in the asymptomatic Saudi population.

National rates of emergency department visits associated with diabetes in Saudi Arabia, 2011-2015.

BACKGROUND: Despite the fact that diabetes is an important component of the burden of disease on the individual and on the national healthcare systems in Saudi Arabia, knowledge of the volume of emergency department (ED) visits for diabetes is unclear. OBJECTIVE: Examine changes in ED visit rates associated with diabetes. DESIGN: Retrospective. SETTINGS: Governmental hospitals. METHODS: Publicly available records of health statistics published by the Saudi Ministry of Health from 2011 through 2015 were used to extract data on ED visits related to diabetes. ED visits associated with diabetes were compared over time and by gender. We calculated diabetes-specific rates per 10000 persons for each sex category by dividing the total number of diabetes-associated ED visits in that category by the sex-specific population. We calculated the rate difference (RD) with 95% CI between 2011 and 2015. MAIN OUTCOME MEASURES: Diabetes-specific rates per 10000 persons for each sex category. RESULTS: Total annual visits to the ED for management of diabetes increased from 617683 cases in 2011 to 748605 in 2015. The annual number of ED visits associated with diabetes increased by 21% over the study period (20% for males and 23% for females). Compared to males, females had a larger increase in visit rates from 240.5 to 249.8 visits per 10000 women over the study years (RD, 9.6 per 10000 persons, 95% CI -16.4 to 26.6 versus 5.7 per 10 000 persons, 95% CI-13.6 to 18.3 ; P=.01). CONCLUSION: Although diabetes-associated ED visit rates dramatically increased in 2012, they remained relatively stable after 2012 to the end of the study period. More effective preventive diabetes programs that prevent the use of ED visits and other expensive healthcare resources among people with diabetes are needed. LIMITATIONS: We had no information on the specific indications for the reported ED visits. These estimates may represent a lower bound on ED visits associated with diabetes since the private sector was not included. CONFLICT OF INTEREST: None.