Institut Penyelidikan Perubatan Molekul - Tesis

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Modulatory Effect Of Thicapa On The Amyloid Precursor Protein Processing Pathways Of Familial Alzheimer’S Disease Using Fibroblast Cell Lines
(2025-04)
Thangeswaran, Danesh
Familial alzheimer’s disease (fad) is a hereditary and irreversible neurological disorder characterised by the accumulation of toxic amyloid-beta (aβ). The prevalence of fad symptoms is concerning as there are no available therapeutic solutions to cure this disease. Thicapa is a novel compound belonging to the tetrahydroisoquinoline (thiq) group of amines, which reported the neuroprotective effects on the ad transgenic drosophila melanogaster (d. Melanogaster) model. Therefore, this study investigated the modulatory effect of thicapa on the amyloid precursor protein (app) processing pathway using the fad patient skin-derived fibroblast cell line (ag06840). This study utilized wst-1 assay to assess cytotoxicity and scavenging potency of thicapa, while qrt-pcr and western blot to analyse gene and protein expressions, respectively. Additionally, protein quantification was performed using elisa and intracellular reactive oxygen species (ros) levels were measured using the dcfda assay. The cytotoxicity assay recorded the insignificant toxic effect of thicapa towards ag06840 and healthy skin-derived fibroblast cell line (gm05879) at three different time points of 24, 48, and 72 hours. The subsequent aβ scavenging assay showed that 50 μm thicapa exerted a potent scavenging effect on aged aβ42 oligomers in the gm05879 fibroblasts cell line.
Production Of Monoclonal Antibodies Against Activin A Receptor Type Ii Like Kinase 1 (Alk-1) By Phage Display
(2025-03)
Nur Alia, Nur Alia
Atherosclerosis, a chronic inflammatory condition affecting the arterial wall, is a leading contributor to cardiovascular diseases (cvds). Low-density lipoprotein (ldl) is a key factor in the pathogenesis of atherosclerosis by promoting plaque formation within arteries. Activate a receptor type ii like kinase 1 (alk-1), a type i receptor of the transforming growth factor (tgf)-β superfamily, has been identified as a promising target for atherosclerosis treatment due to its role in the regulation of ldl levels. This study aimed to generate monoclonal antibodies (mabs) against alk- 1 using phage display technology for potential therapeutic applications. The alk-1 antigen was successfully expressed and purified, and its functionality was confirmed through binding assays with its ligand, bone morphogenetic protein-9 (bmp-9), and ldl. Biopanning of a human naïve single-chain variable fragment (scfv) antibody phage library against alk-1 was performed, resulting in the isolation of three unique scfv clones 4e, 9f, and 7c. Sequence analysis demonstrated that these clones pertained to distinct vdj gene families and exhibited varying complementaritydetermining region (cdr) lengths. Bioinformatics tools were used to predict the solubility of the scfv clones, which were subsequently expressed and purified from e. Coli.
Insilico, Invitro,And Invivoanalysesofdown-Regulated Microrna-484 Inhela Cellstreated With Polyalthia Longifoliamethanol Leaf Extract As Regulators Ofapoptosis
(2025-06)
Niu, Jiaojiao
This study aimed to investigate the diagnostic and prognostic relevance of miR-484 in CC using integrated bioinformatics, and to functionally validate its role in regulating apoptosis through both in vitro and in vivo models. Particular focus was placed on the interaction between miR-484 and Polyalthia longifolia methanol extract (PLME), a natural compound previously shown to induce apoptosis in HeLa cells via miR-484 downregulation.
Effect Of Murine Norovirus-3 (Mnv-3) Infection On Atherosclerosis Development In Macrophage Cell Lines And C57bl/6 Mice
(2024-12)
Rumah, Muhammad Hayatuddeen
Atherosclerosis, a chronic inflammatory disease, is characterized by lipid build-up in the arterial wall and regulated by innate and adaptive immune responses. Significant roles in the disease’s onset and progression are played by macrophages and various t-cell subsets. The effect of murine noroviruses-3 (mnv-3) infection on atherosclerosis development was investigated in this study using in vitro and in vivo models. In the in vitro model, atherosclerosis was induced by oxldl, whereas in the in vivo model, a cholesterol-rich diet was used to induce atherosclerosis in c57bl/6 mice. In the in vitro experiment, a reduction in atherosclerosis was observed in pre-infected raw 264.7 cells due to decreased tce , pro-inflammatory cytokine secretion (tnf-α, il-6, il-1β), and macrophage surface protein expression (cd88, cd36, cd11b) levels. Conversely, mnv-3 infection promoted atherosclerosis in post-infected raw 264.7 cells by elevating tce levels, boosting tnf-α, il-6, il-1β secretions, and promoting cd88, cd36, cd11b expression levels. Lastly, no significant alteration in atherosclerosis was observed in co-infected raw 264.7 cells, as tce levels, tnf-α, il-6, il-1β secretions, and cd88, cd36, cd11b expression levels were not significantly affected. In thp-1 derived macrophages, mnv-3 promoted atherosclerosis by boosting tnf-α, il-6, il-1β secretions and promoting cd88, cd36, cd11b expression levels.
A Single Domain Antibody Derived From Antibody Phage Display Library Fused With Cell Penetrating Peptide For The Clearance Of Il-23
(2024-10)
Abdo, Ahmad Ismail Khaled
Il-23 is a two-subunit proinflammatory cytokine that plays an important role in shaping the immune response. It is associated with several autoinflammatory diseases by generating sustained inflammatory loops through the il-17 and il-22 arms leading to tissue damage. Antibody neutralization of il-23 was proven to be effective in breaking these loops and ameliorating disease. However, antibodies have limited tissue penetration and tend to elicit anti-drug antibodies due to their large size. Additionally, anti-il-23 antibodies target only one subunit of the cytokine, either p40 or p19, leaving the other one unneutralized. This study aimed to generate an anti-il-23 single domain antibody (sdab) that leads to antigen-clearance. Two methods of antigen clearance were explored, the isolation of a recycling sdab by phage display and conjugation of sdab to cell penetrating peptides (cpps). The sdab was generated by phage display biopanning against one of the il-23 subunits, p19, which was expressed in e.Coli fused to gamillus (gam) protein as a stabilizer. Biopanning failed to isolate specific, high-affinity recycling binders for p19, however, a specific and high-affinity standard binder for p19 was successfully isolated. The isolated sdab, designated as h11, was conjugated with two cpps, r9 and tatk, respectively. Elisa results of p19 binding to purified h11, h11-r9, and h11-tatk , showed that cpps conjugation did not alter the h11 binding affinity. The functionality of the purified sdabs was further examined to evaluate the cpp fusion effect.

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