Pusat Pengajian Sains Kesihatan - Tesis

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    Assessment of cytokine secretions by monocytes in the presence of synovial fluid-derived exosomes
    (2025-01)
    Bahri, Tengku Qashrina Adriana Tengku Shaifful
    Osteoarthritis (OA) is a prevalent degenerative joint disease marked by inflammation and cartilage deterioration. Synovial fluid-derived exosomes are emerging as key modulators in OA pathogenesis, influencing immune responses and cytokine secretion. This study aimed to assess cytokine secretions, specifically soluble intercellular adhesion molecule-1 (sICAM-1), complement component 5a (C5a), and macrophage migration inhibitory factor (MIF), by monocytes in the presence of synovial fluid-derived exosomes. Exosomes were isolated from the synovial fluid of late-stage OA patients through ultracentrifugation and characterised by Western blot and nanoparticle tracking analysis (NTA). Exosome size has been confirmed between 30 to 150 nm by NTA. Additionally, exosomes expressed tetraspanin markers CD9, CD63, CD81, and HSP70 as demonstrated by Western blot. Monocytes isolated from healthy donor peripheral blood, were cultured with exosomes at various ratios (1:10, 1:20, and 1:40) and time points (24 and 48 hours). Cytokine levels were quantified using enzyme-linked immunosorbent assay (ELISA). The results of this study showed that monocyte-exosome interactions influenced cytokine secretion in a time- and dose-dependent manner. sICAM-1 and C5a exhibited a declining trend with prolonged incubation, except at higher exosome concentrations, where C5a secretion was increased. MIF levels peaked after 48 hours, suggesting delayed cytokine induction. These findings highlight the immunomodulatory role of exosomes in OA, providing insight into the inflammatory processes underlying disease progression
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    Changes in ph of digestive vacuole of plasmodium falciparum treated with pipecolisporin and analogue ii peptide
    (2025-01)
    Fauzi, Nurul Adila Ahmad
    Malaria is a severe and fatal disease caused by Plasmodium spp. and remains one of the leading global causes of morbidity and mortality. The emergence of drug-resistant P. falciparum in various countries has necessitated an effort to discover new antimalarial drugs targeting different pathways. Research on the potential of pipecolisporin and analogue II as an antimalarial agent has remained limited. Therefore, this study aimed to fill this knowledge gap by investigating the antimalarial activity of pipecolisporin and analogue II peptides. The antimalarial potential of pipecolisporin and analogue II against the chloroquine-sensitive strain (3D7) of P. falciparum was assessed based on the calculation of parasitaemia using Giemsa stained-blood smears. The pipecolisporin and analogue II exhibited highly active antimalarial activity with an IC50 value of 0.4770 and 0.1170 μM, respectively. A further investigation focused on the effect of pipecolisporin and analogue II towards the pH of the mid trophozoite stage parasite’s digestive vacuole, employing a flow cytometry-based technique with fluorescein isothiocyanate-dextran (FITC-dextran) as a pH ratiometric probe. The results revealed no increase in pH following pipecolisporin and analogue II treatment. Suggests that pipecolisporin and analogue II might not have the mechanism to alter the digestive vacuole’s pH through the inhibition of V-type H+-ATPase that regulates the acidification of the vacuole. Overall, this study provides crucial evidence of pipecolisporin and analogue II capability as a promising antimalarial candidate
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    Cytotoxicity study on the combination of cisplatin and gallic acid on cervical cancer cells (hela)
    (2025-01)
    Ramlan, Nur Iman Nafisa
    Cervical cancer is the fourth most common cancer among women worldwide and remains a major health concern. Cisplatin, a chemotherapeutic agent, is often limited by severe side effects and the development of resistance. Combining cisplatin with natural compounds, such as gallic acid, may enhance therapeutic efficacy while reducing toxicity. This study aimed to evaluate the cytotoxic and anti-migratory effects of cisplatin combined with gallic acid on cervical cancer cells (HeLa). Cytotoxicity was assessed using the MTT assay the half-maximal inhibitory concentration (IC50). Serial dilution of cisplatin, starting from its IC50 was combined with a fixed concentration of gallic acid at its IC50. The combination effects were analyzed using CompuSyn software to assess potential synergy, additivity, or antagonism. The combination with the greatest synergistic effect was then chosen for wound healing assay, to examine the anti-migratory effects of the combination. The IC50 of cisplatin and gallic acid for HeLa cells were 25.12 μg/mL and 85.70 μg/mL, after 24 hours, which decreased to 1.786 μg/mL and 13.27 μg/mL at 48 hours. For WRL-68 cells, the IC50 values of cisplatin and gallic acid were 28.02 μg/mL and >100 μg/mL at 24 hours, decreasing to 8.842 μg/mL and 21.06 μg/mL at 48 hours. All combinations of cisplatin and gallic acid significantly inhibited HeLa cell proliferation with combination index values below 1, indicating a synergistic effect. Furthermore, the combination exhibited anti-migratory effects, showing the lowest percentage of wound closure compared to control and single treatment groups. These findings suggest that combining cisplatin with gallic acid holds potential as a novel therapeutic strategy to enhance cervical cancer treatment outcomes
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    Insights into the interaction between statins and monocarboxylate transporter 1: a molecular docking approachl
    (2025-01)
    Hassan, Nur Amirah Mumtaz Abd Jalil
    Statins are commonly prescribed in the management of cardiovascular diseases; however, they can lead to statin-associated muscle symptoms (SAMS), which are often related to mitochondrial dysfunction. Monocarboxylate transporter (MCT1) is a proton-linked monocarboxylate transporter that facilitates the cellular uptake of statins, influencing their pharmacokinetics and potential effects on cellular metabolism and mitochondrial function. Although direct interactions between statins and MCT1 are not well-documented, emerging evidence suggests that mitochondrial dysfunction associated with statins may involve MCT1-mediated mechanisms, potentially through alterations in lactate transport and metabolic regulation.. This study explores the molecular interactions between statins and MCT1, focusing on their binding affinities and the subsequent effects on mitochondrial function and gene regulation. The 3D structure of MCT1 from Rattus norvegicus was modeled using the Swiss-Model database, based on similar sequences from Mus musculus. Molecular docking analyses, employing both blind and specific docking methods, indicated that atorvastatin lactone had the highest binding affinity to MCT1 (-8.7 kcal/mol and -9.2 kcal/mol, respectively), followed by rosuvastatin lactone (-7.5 kcal/mol and -7.9 kcal/mol), simvastatin lactone (-7.7 kcal/mol for both), pravastatin lactone (-7.4 kcal/mol for both), and simvastatin acid (-5.7 kcal/mol and -6.0 kcal/mol). Of all statins analyzed, simvastatin acid does not have any hydrogen bonds with amino acid residues of MCT1 thus could explained its lowest binding affinity. It unlike other statins. Important binding residues, including LEU132, TYR70, and THR388, were identified as essential for ligand interactions. By identifying the key molecular interactions that contribute to SAMS, this study establishes a solid framework for early prediction of MCT1 involvement during the pathology process
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    Evaluation of the effects of kaffir lime and lemon myrtle essential oils on the digestive vacuole of plasmodium falciparum
    (2025-01)
    Zaki, Nor Alia Sofea Mohd
    Malaria is a severe and fatal disease caused by Plasmodium spp. and remains one of the leading global causes of morbidity and mortality. The emergence of drug- resistance P. falciparum in various countries has necessitated an effort to discover new antimalarial drugs targeting different pathways. Medicinal plants have been a fundamental part of traditional medicine for centuries. Natural compounds extracted from these plants have shown great promise in serving as lead candidates for drug development. Despite this, research on the effects of kaffir lime and lemon myrtle essential oils on the digestive vacuole of P. falciparum remains largely unexplored. Therefore, this study aimed to fill this knowledge gap by investigating the antimalarial activity of kaffir lime and lemon myrtle essential oils. The antimalarial potential of the kaffir lime and lemon myrtle against the chloroquine-sensitive strain (3D7) of P. falciparum was assessed by using in vitro antimalarial assay. The kaffir lime and lemon myrtle essential oils demonstrated weak or no antimalarial activity with IC50 values of 150.6 μg/mL and 273.5 μg/mL, respectively. Additionally, the treatment with different concentrations of kaffir lime and lemon myrtle essential oil showed no changes on the digestive vacuole pH. This study revealed that the pH of the digestive vacuole treated with kaffir lime and lemon myrtle essential oils are stable and comparable to the untreated control. This suggests that these essential oils do not alters the digestive vacuole pH of P. falciparum