Institut Perubatan & Pergigian Termaju - Tesis

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    Characterisation Of Biogenic Silver Nanoparticles-garcinia Atroviridis Toxicological Effects In Normal And Cancer Human Lung Cells.
    (2024-09)
    Muhamad, Musthahimah
    Silver nanoparticles (AgNPs) synthesized from plants are increasingly used across various industries, including the pharmaceutical and food sectors. This widespread use has raised concerns about their safety profiles. This study aimed to examine the toxic effects and mechanisms of biogenic silver nanoparticles (AgNPs-GA) synthesized using Garcinia atroviridis leaf extract on human lung cancer cells (A549) and normal lung cells (BEAS-2B) in vitro. Cytotoxicity was evaluated using the MTT assay to determine the IC50 values of AgNPs-GA in both cell types. The IC50 values were applied to treat the respective cells for evaluating reactive oxygen species (ROS) production, apoptosis, DNA damage, silver ion levels, and cellular uptake using CM-H2DCFDA assay, DAPI and AOPI double staining, comet assay, ICP-OES, and TEM, respectively. The mRNA expression and metabolic profiles were further assessed using quantitative real-time PCR and untargeted metabolomics based on ultra-high-performance liquid chromatography-Orbitrap mass spectrometry (UHPLC-Orbitrap-MS), respectively. The results showed that AgNPs-GA inhibited 50% of the growth in A549 and BEAS-2B cells, with IC50 values ranging from 20–28 μg/ml and 12–35 μg/ml, respectively. The selective index (SI) values of AgNPs-GA were below 3, classifying it as a non-selective cytotoxic agent, as it induced general toxicity in both cancerous and non-cancerous cell types. AgNPs-GA were primarily internalized and deposited within lysosomes, nucleus, and mitochondria, leading to an increased release of ionic silver (Ag+) inside both cells.
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    Preclinical Evaluation Of Mechanisms Underlying Chemotherapy-Induced Ovarian Dysfunction And The Restorative Potential Of Mesenchymal Stem Cells In Premature Ovarian Insufficiency
    (2024-07)
    Zhang, Shenghui
    Conventional chemotherapy, while effective in eliminating cancer cells, unfortunately, inflicts collateral damage on normal cells with heightened proliferative capacity, particularly causing ovarian toxicity. This study delves into elucidating the underlying mechanisms of chemotherapeutic drug-induced ovarian damage, aiming to pave the way for the development of fertility-preserving adjuncts for female patients undergoing conventional cancer treatment. In this context, mesenchymal stem cells-extracellular vesicles (MSC-EVs), as promising cell-free therapeutic agents, demonstrate notable advantages in addressing ovarian dysfunction. However, the precise mechanisms through which MSC-EVs ameliorate chemotherapy-induced ovotoxicity remain unclear. The primary objectives of this study are to elucidate the toxicity of chemotherapeutic drugs on the ovary, unravel the potential mechanisms leading to follicle loss, and investigate the therapeutic potential of Menstrual blood-derived endometrial stem cell (MenSC)-EVs transplantation in alleviating chemotherapy-induced ovarian dysfunction.
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    Construction Of Gene Expression Model On Relationship Between Candida Albicans And Colorectal Cancer
    (2024-07)
    Zhang, Haoling
    This study primarily explores the paradox of whether Candida albicans (C. albicans) promotes or inhibits the development of Colorectal cancer (CRC), focusing on its metabolites mixture for relevant arguments. Differential gene analysis was initially employed to construct a model of differential gene-related prognostic genes (mRNAs) and was internally and externally validated within biological information databases. The impact of metabolites mixture on CRC cell viability was assessed utilizing the CCK-8 assay at different time intervals (12, 24, 48, and 72 hours) and concentrations (OD600 approximately 0.2, 0.3, 0.4). qRT-PCR was employed to assess the mRNA expression levels of prognostic genes EHD4, LIME1, GADD45B, TIMP1, and FDFT1 in each group of CRC cells. Cell invasion and migration capabilities were evaluated through Transwell experiments. Finally, the eATP content was determined using an ATP detection kit. This study identified a total of 213 differentially expressed genes. A prognostic model containing 5 specific mRNA markers, namely EHD4, LIME1, GADD45B, TIMP1, and FDFT1, was constructed. C. albicans metabolites mixture reduced CRC cell activity. qRT-PCR results showed that compared to normal colonic epithelial cells, LIME and EHD4 were downregulated in CRC cells, while FDFT1 expression was significantly upregulated.
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    Optimisation Of Induced Pluripotent Stem Cells Derivation From Human Cord Blood And Its Application For Cardiac Regeneration In Cryoinjured Rat Model
    (2024-08)
    Universiti Sains Malaysia
    Cardiomyocyte therapy was considered the only option to repopulate myocardial loss, but challenges existed in achieving effective replenishment of functional cardiomyocytes that could translate into clinical benefits. This study aimed to examine the use and function of pre-epicardial cells in cardiomyocyte therapy in vivo. Cryopreserved cord blood was used to generate human-induced pluripotent stem cells (hiPSCs) to harness the ‘youthfulness’ of foetal cells. The generated hiPSCs were also used to produce cardiomyocytes (CMs) and pre-epicardial cells (PECs) with high differentiation efficiency using established protocols. To confirm the effects of PECs on cardiomyocytes, both differentiated CMs and PECs were co-cultured for 6 days, and the proliferation and role of Hippo signaling were assessed. PECs (1x10⁶ cells/100 μl) were also combined with CMs (1x10⁶ cells/100 μl) to treat cryoinjured rat hearts after 1 month. Cardiac functions were assessed using Millar Pressure Volume Loop cardiac hemodynamics analysis. Differences between groups were considered significant when p < 0.05 using ANOVA. Frozen CD34 cells were successfully reprogrammed into hiPSCs with consistent expression of pluripotent markers. The generated hiPSCs demonstrated multilineage differentiation ability, forming cardiomyocytes, dopamine neurons, and early endodermal cells.
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    Physico-Mechanical And Biological Evaluation Of Three-Dimensional Printed Thermoplastic Polyurethane And Polylactic Acid Scaffold For Tracheal Tissue Engineering
    (2023-02)
    Samat, Asmak Abdul
    Surgical restoration of extensive tracheal lesions is complicated, and it necessitates the use of a biocompatible, mechanically stable, and non-toxic material that degrades gradually to overcome the limitation of allografts. A three-dimensional (3D) printed tracheal scaffold produced from polymers is one option for addressing some of the challenges in tracheal transplantation. Polymer blending is one approach for creating material with specific properties for a trachea scaffold. The goal of this study was to evaluate the physical, mechanical, and biological properties of thermoplastic polyurethane (TPU) and polylactic acid (PLA) blend as prospective tracheal replacement materials. Both materials are well-known for their promising properties when utilised independently, thus broadly employed in various applications, especially in the biomedical field. It is hypothesised that combining the two materials and the subsequent 3D printing method produces a composite with suitable qualities for tracheal replacement. Different TPU and PLA compositions were melt-blended and characterised for their physical and mechanical properties,