Saudi Cultural Missions Theses & Dissertations

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    Insights into Human Oviduct Physiology and Inflammatory Stimuli Using In Vitro Organoids
    (University of Manchester, 2025) Alkasih, Mohannad; Stevens, Adam
    The human oviduct is a crucial organ of the female reproductive tract that plays a key role in the early reproductive events. It includes four distinct segments and each segment contributes uniquely in the function of the oviduct. The epithelial lining of the oviduct is of key importance for human reproduction as it regulates the tubal environment, including epithelial-sperm interaction. In addition, the luminal fluid of the oviduct provides an optimum microenvironment for embryo development. It contains molecules that contribute to support gamete viability and preimplantation development. Chlamydia trachomatis is a bacterium that causes chlamydial infection and one of the most common causes of sexually transmitted disease worldwide. This asymptomatic bacterial infection may remain undiagnosed or untreated, which in turn ascend to the upper female reproductive tract and infect the oviduct. Infection of the oviduct can result in scarring and damaging inflammation within the microenvironment of the oviduct. The release of pro-inflammatory cytokines during Chlamydial infection may lead to functional damage of the oviduct. Despite the importance of the oviduct, detail on how oviduct responds to the release of pro-inflammatory cytokines during infections is not well known. This project has used in vitro oviduct organoids to assess whether organoids could be engineered to allow the investigation of sperm-oviduct interaction and investigates the impact of inflammatory mediators on the epithelial cells and luminal fluid of the oviduct. The project has explored the genomic and physiological responses of oviduct organoids. The data showed that the in vitro organoid model clearly recapitulates the in vivo oviduct tissue by expressing the key cellular structures. A complete inversion of the oviduct organoids is achievable for future research on gamete-oviduct interaction. IFNγ is an effective inflammatory mediator and has a significant impact on the epithelial cells of the oviduct. The downregulation of ANXA5 might play a key role in infertility in patients with Chlamydial infection. Oviduct organoids provide a promising platform and a powerful tool for future investigations and to address questions regarding reproductive system.
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    In-Vitro Effects of Recombinant IL-37 protein on Bladder cancer cell line Growth and Proliferation
    (University of East London, 2024-08) Alamri, Ashwaq; Gobena, Edessa
    Introduction: Interleukin-37 (IL-37) is a cytokine of the IL-1 family, recognized for its anti-inflammatory and immunomodulatory functions. Despite growing interest in IL-37’s role in different types of cancers, its impact on bladder cancer growth and proliferation has not been thoroughly investigated. This study aims to explore the effects of recombinant IL-37 protein on the viability, proliferation, and apoptosis of T24 bladder cancer cell lines, addressing a significant gap in current cancer research. Methods: In this in vitro study, T24 bladder cancer cells were treated with different concentrations of recombinant IL-37 protein (1 μg/ml, 0.5 μg/ml, and 0.25 μg/ml) with negative control (0 μg/ml). Cell viability and apoptosis were assessed using flow cytometry, and the levels of pro- inflammatory cytokines IL-6 and IL-8 in the cell culture supernatants were quantified using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test to determine the significance of the results. Results: The results showed that IL-37 induces apoptosis in a dose-dependent manner, with the highest concentration (1 μg/ml) significantly reducing the percentage of viable cells from 90% to 71% and increasing the apoptotic cell population from 7% to 27%. Additionally, IL-37 treatment modulated the secretion of IL-6 and IL-8, with a significant increase in IL-6 production at 0.25 μg/ml (P ≤ 0.05) compared to the control. However, IL-37 did not significantly inhibit IL-8 production across the different treatment groups. (P ≤ 0.05). Conclusion: This study demonstrates that IL-37 not only promotes apoptosis in bladder cancer cells but also alters the tumor microenvironment by modulating cytokine secretion. These findings suggest that IL-37 may hold therapeutic potential as a novel approach to bladder cancer treatment. Further research is necessary to validate these results in vivo and to elucidate the precise molecular mechanisms through which IL-37 exerts its anti-tumor effects.
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