Institut Penyelidikan Perubatan Molekul - Tesis
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- PublicationRegioselective Biosynthesis Of Reveromycin Derivatives By Cytochrome P450revi Mutant In Actinacidiphila Reveromycinica Sn-593(2025-09)Yong, Ya FenReveromycin A (RM-A) (1) has a 6,6-spiroacetal core structure that is important for its biological activity. However, 1 undergoes a spiroacetal rearrangement to form RM-B (2) with a 5,6-spiroacetal core, which exhibits reduced bioactivity. This undesired rearrangement is partly due to the hemisuccinate moiety at the C18 position of 1. In 1 biosynthesis, P450revI catalyzes the C18-hydroxylation of RM-T (3), which is essential for its subsequent hemisuccinylation to generate 1. This study aimed to alter the P450revI regioselectivity to improve the stability of the 6,6-spiroacetal core and expand the structural diversity of RMs.
- PublicationCharacterizations, Antigenicity, And Immunogenicity Of Extracellular Vesicle Proteins From Iron-Deprived Mycolicibacterium Smegmatis(2025-09)Jayaram, MehaleneTuberculosis (TB), the world's leading infectious killer, remains a major global health challenge. BCG, the only available vaccine, provides limited protection that wanes over time. Extracellular vesicles (EVs) from Mycobacterium tuberculosis (MTB) have shown vaccine potential, but their isolation is hindered by slow bacterial growth and biohazard risks. This study used Mycolicibacterium smegmatis (MSMEG), a fast-growing, non-pathogenic model organism, to produce EVs under iron-depleted conditions. These EVs were evaluated for stability, antigenicity using three pooled TB positive patient sera and their potential as a BCG booster vaccine in mice. Lyophilized EVs maintained antigenicity and structural stability, as confirmed by nanoparticle tracking analysis, transmission electron microscopy and western blotting.
- PublicationCharacterisation Of Recombinant Igg Binding Protein, Fcγriia For Biosensor Development(2025-09)Gan, Shin YiAntibodies play an important role in diagnostic applications due to their high specificity and affinity towards target antigens. However, in biosensor development, particularly for point-of-care (POC) diagnostics, the method of antibody immobilisation on sensor surfaces remains a critical bottleneck influencing assay sensitivity, reproducibility, and overall performance. Traditional techniques, such as passive adsorption or random covalent coupling, often result in poorly oriented and unstable antibodies. Consequently, assays showed high background noise, reduced binding activity, poor reproducibility, and relatively high detection limits, typically in the microgram-per-millilitre to high nanogram-per-millilitre range. Such shortcomings limit the reliability and clinical application of electrochemical immunosensors. To address these challenges, this study investigated the application of recombinant human IgG Fc receptors, namely FcγRIA, FcγRIIA, and the neonatal Fc receptor (FcRn), as site-specific antibody capture ligands for electrochemical biosensing.
- PublicationEvaluation Of The Anti-Aging Effects Of Polyalthia Longifolia Leaf Extract In D-Galactose-Induced Aging Rat Model(2025-04)Ismaila, MuhammadAging is closely associated with oxidative stress, telomere shortening, and cellular senescence, contributing to neurodegeneration and cognitive decline. Polyalthia longifolia, a polyphenol-rich plant with strong antioxidant properties, has been traditionally used for various therapeutic purposes. This study investigated the anti-aging and neuroprotective potential of polyalthia longifolia leaf methanol extract (plme) at 500 mg/kg/day for four weeks against d-galactose-induced aging rat model. Phytochemical analysis of plme revealed high phenolics (88.23 ± 0.001 mg gae/g) and flavonoids (66.97 ± 0.002 mg qe/g) contents, while ftir spectra identified key functional groups (-oh, -ch, c=o, and n-h), indicative of bioactive compounds. Plme demonstrated strong in vitro antioxidant activity, effectively scavenging dpph, h₂o₂, and o₂•– radicals, with ic₅₀ values of (74.0 ± 6.0; 54.0 ± 3.0; and 32.8 ± 1.0) μg/ml, respectively. In vivo, d-galactose administration effectively induced aging-related oxidative stress, significantly (p < 0.05) elevating serum malondialdehyde (mda: 9.66 ± 1.22 nmol/ml) while decreasing glutathione (gsh: 4.26 ± 1.61 μmol/ml) levels, and reducing superoxide dismutase (sod: 82.16 ± 3.01 u/ml) and catalase (cat: 11.71 ± 4.02 u/ml) activities. In contrast, plme treatment significantly mitigated these effects, lowering mda levels (5.32 ± 0.64 nmol/ml) while increasing gsh (7.22 ± 2.87 nmol/ml) concentration, as well as enhancing sod (106.09 ± 4.13 u/ml) and cat (15.22 ± 3.12 u/ml) activities.
- PublicationComparative Analysis Of Cysts And Trophozoites Of Giardia Duodenalis Using Proteomic And Bioinformatic Analysis(2025-05)Aziz, Ahmad Fudail EiyadGiardia duodenalis is a protozoan parasite responsible for giardiasis, a widespread gastrointestinal disease that significantly affects public health, particularly in developing regions. The parasite alternates between the motile trophozoite and the cyst stage, with transmission primarily occurring through contaminated water. Giardiasis causes symptoms such as diarrhea, malabsorption, and weight loss, severely impacting children’s health. Current diagnostic methods lack sensitivity and specificity, and treatment options are complicated by emerging drug resistance. This study aims to provide a comprehensive proteomic analysis of g. Duodenalis trophozoites and cysts, focusing on identifying key proteins and pathways for improving diagnostic approaches particulary for antigen tests by narrowing notable proteins that highly involved in the life cycle of g. Duodenalis through proteomic and bioinformatics analyses. Protein extraction methods (sds-lysis, urea-lysis, sonication, and rapigest-aided sonication) were optimized, with urea-lysis yielding the high protein concentrations and better protein separation. Mass spectrometry identified 712 non-redundant proteins, with 145 unique to trophozoites, 156 unique to cysts, and 57.7% common to both stages.