Thymoquinone reversed doxorubicin resistance in U87 glioblastoma cells via targeting PI3K/Akt/mTOR signaling.

Natural compounds such as thymoquinone (TQ) have recently gained increasing attention in treating glioblastoma (GBM). However, the effects of TQ in reversing drug resistance are not completely understood. Therefore, we aimed to examine TQ impacts on GBM cells with doxorubicin (DOX) resistance and the involvement of the PI3K/Akt/mTOR pathway. GBM cancer U87 and U87/DOX (resistant cells) cells were exposed to DOX and TQ, and cell proliferation was assessed by the MTT assay. ELISA was applied to evaluate cell apoptosis. The expression of apoptotic mediators such as Caspase-3, Bax, Bcl-2 and PI3K, Akt, mTOR, P-gp, and PTEN was assessed via qRT-PCR and western blot. We found that a combination of TQ and DOX suppressed dose-dependent cell growth capacity in cells and increased the cytotoxic effects of DOX in resistant cells. In addition, TQ treatment increased DOX-mediated apoptosis in U87/DOX cell lines via modulating the pro- and anti-apoptotic markers. A combination of TQ and DOX upregulated PTEN and downregulated PI3K, Akt, and mTOR, suppressing this signal transduction in resistant cells. In conclusion, we showed TQ potentiated doxorubicin-mediated antiproliferative and pro apoptotic function DOX-resistant glioblastoma cells, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.

Self-Medication with Antibiotics during COVID-19 in the Eastern Mediterranean Region Countries: A Review.

Self-treatment with medicines including treatment with antibiotics is a growing global concern, as it can cause public health problems, such as antibiotic resistance and drug toxicity. Therefore, the significance of the self-medication impact of COVID-19 in any region can have an influence on the prevalence of such problems. The review aimed to investigate the self-treatment with antibiotics among the general population in Eastern Mediterranean region countries during COVID-19 pandemic. A comprehensive review of literature in four databases was conducted for the pandemic period from January 2020 to the end of March 2022. Nine studies related to self-treatment with antibiotics were found. The studies were homogeneous in terms of assessing the antibiotic self-treatment usage during the COVID-19 pandemic among the general population and among community pharmacies. The prevalence of self-treatment with antibiotics ranged from 20.8% to 45.8% between the studies. The main reasons for that were cost-saving, fear of COVID-19 infection, quarantine, and ease of accessibility without time limits. Antibiotic self-treatment has been high during the COVID-19 pandemic; however, it was less reported during the study period than before the time of the pandemic. There is a need for more restrictions on dispensing antibiotics from community pharmacies. In addition, there is a need to raise awareness among the population regarding self-treatment with antibiotics.

Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran.

Objectives Type 1 diabetes is an autoimmune disease. Its most important immunologic markers are pancreatic beta-cell autoantibodies. This study aimed to determine diabetes mellitus antibodies frequency among children and adolescents with type 1 diabetes. Methods This descriptive study evaluated the frequency of four diabetes autoantibodies (glutamic acid decarboxylase 65 autoantibodies [GADA], islet cell autoantibodies [ICA], insulin autoantibodies [IAA], tyrosine phosphatase-like insulinoma antigen-2 antibodies [IA-2A]) and their serum level in children and adolescents diagnosed with type 1 diabetes mellitus at the diabetes department of Bou-Ali-Sina Hospital and Baghban Clinic, Sari, Iran, from March 2012 to March 2018. The relationship between the level of different antibodies and age, gender, and diabetes duration were determined. A two-sided p value less than 0.05 indicated statistical significance. Results One hundred forty-two eligible patient records were screened. The average age at diabetes diagnosis was 4.2 ± 4.4 years. The median duration of diabetes was 34.0 (12.7-69.7) months. 53.5% of patients were female, and 81.7% of them had at least one positive autoantibody, and ICA in 66.2%, GADA in 56.3%, IA-2A in 40.1%, and IAA in 21.8% were positive. The type of the autoantibodies and their serum level was similar between females and males but there was a higher rate of positive autoantibodies in females. The level of IA-2A and ICA were in positive and weak correlation with age at diagnosis. Conclusions More than 80% of pediatric and adolescent patients with type 1 diabetes were autoantibody-positive. ICA and GADA were the most frequently detected autoantibodies. The presence of antibodies was significantly higher in females.