Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed | YÖK Tez

Permanent URI for this communityhttps://hdl.handle.net/20.500.14627/3

Browse

Now showing 1 - 2 of 2

Investigation of Novel Nimesulide Derivatives Against Breast Cancer
(Academic Press Inc Elsevier Science, 2025) Birgul, Kaan; Atlihan, Irem; Dere, Damla; Yelekci, Kemal; Tiber, Pinar Mega; Orun, Oya; Kucukguzel, S. Guniz
This study focused on the synthesis of novel nimesulide semicarbazone derivatives and the evaluation of their cytotoxic potential against luminal-A (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines. Additionally, their effects on mitochondrial membrane potential (MMP), apoptosis, and mitogen-activated protein kinase (MAPK) pathway modulation were investigated. Breast cancer remains the most prevalent malignancy among women, with luminal-A and triple-negative subtypes posing significant therapeutic challenges due to drug resistance and the lack of effective targeted treatments. The MAPK pathway plays a crucial role in breast cancer progression, making its inhibition a promising therapeutic approach. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly nimesulide, have demonstrated anticancer potential beyond their well-established anti-inflammatory properties. Accordingly, the semicarbazone moiety was incorporated into the molecular scaffold to enhance the antiproliferative efficacy of nimesulide derivatives, as it has been reported to exhibit cytotoxic and apoptosis-inducing effects across various cancer cell lines. A series of nimesulide semicarbazone derivatives (5a-m) were synthesized through multi-step reactions and characterized using elemental analysis, FT-IR, 1H NMR, 13C NMR and Mass spectroscopy (5e). In silico studies were performed to predict their binding affinities to MAPK12. The cytotoxic effects of the synthesized compounds were assessed by determining IC50 values in MCF-7 and MDA-MB-231 cell lines (CCK8 test). Compounds exhibiting strong cytotoxic activity were further examined for their impact on MMP depolarization (JC-1 assay), apoptosis induction (Annexin V-FITC/PI staining), and MAPK pathway modulation (Western blotting of p-ERK and ERK protein). Molecular docking results indicated that the synthesized compounds exhibited favorable interactions with MAPK12, with compound 5e showing one of the highest binding affinity (-9.29 kcal/mol, Ki = 0.154 mu M). Cytotoxicity assays revealed that compound 5e had the lowest IC50 values (11.77 +/- 0.26 mu M in MCF-7; 20.72 +/- 0.25 mu M in MDA-MB-231), demonstrating significantly higher cytotoxicity than nimesulide. JC-1 assays confirmed that compound 5e induced MMP depolarization at higher concentrations, suggesting apoptosis activation. Flow cytometry analysis further validated a substantial increase in apoptotic cell populations following treatment with compound 5e. Western blot results showed a dose-dependent decrease in p-ERK levels in both MCF-7 and MDA-MB-231 cells, confirming MAPK pathway inhibition. These findings support that nimesulide-based semicarbazones, particularly compound 5e, exhibit potent antiproliferative and pro-apoptotic activity via MAPK pathway modulation, offering a promising avenue for the development of targeted breast cancer therapies.
Ramadan Fasting and Seizure Activity in Adults with Epilepsy: A Systematic Review and Meta-Analysis
(Academic Press Inc Elsevier Science, 2026) Ibrahim, Ismail A.; Shaaban, Sally; Elewa, Mandy; Rahman, Muhammad Samir Haziq Bin Abd; Mohamed, Lobna Ahmed; Talaia, Ahmed M.; Khoo, Ching Soong
Purpose: Ramadan fasting in Muslims entails abstaining from food and fluids from dawn to sunset, which can influence sleep patterns, medication timing, and food intake. Building on evidence that ketogenic diets and intermittent fasting may improve seizure control, we aim to analyze the link between intermittent Ramadan fasting in adults with epilepsy and seizure activity. Method: We systematically searched PubMed, Scopus, Web of Science, Cochrane Library, and Embase between 2000 and January 2025 for articles that appeared between these dates. The terms used for searching included fasting in Ramadan with epilepsy or seizures. The seizure frequency and seizure status of the participants are the outcomes that we analyzed. Two reviewers independently screened and extracted data, with a third resolving any differences that arose between them. Meta-analysis was done using the random-effects model with statistical heterogeneity using the I2 statistic. Results: Of the 1485 articles, only eight were found to be relevant, and 4 of these included 564 patients who met the inclusion criteria. The analysis of the pooled data demonstrated that 61.1% of patients remained seizure-free throughout Ramadan (95% CI: 38.8%-83.4%), with considerable heterogeneity (I2 = 87.7%). Seizure risk was higher in patients on polytherapy with poor baseline seizure control, increased fasting times, or high potassium levels. In contrast, extended seizure-free intervals and increased sleep duration pre-Ramadan were good predictors of safe fasting, and each seizure-free week increased the chance of remaining seizure-free by 10%, as did each extra hour of sleep by 30%. Seizure frequency increases were caused by interruption of daily rhythms, psychological tension, tiredness, and extended fasting. Conclusion: While many patients remained seizure-free during Ramadan, high study variability highlights the need for standardized research. With proper medical supervision, fasting may be safely practiced for selected epilepsy patients.

Browse

Browsing Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed | YÖK Tez by Publisher "Academic Press Inc Elsevier Science"