Pusat Pengajian Sains Kesihatan - Monograf

Browse

Now showing 1 - 5 of 851

Generation of in-silico DNA-aptamer as synthetic bioreceptor targeting PIVKA-II for early liver cancer detection
(2026-01)
Pranto, Shivnath Das
Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a clinically validated biomarker for hepatocellular carcinoma; however, its selective detection remains challenging due to structural homology among prothrombin-derived proteins. In this study, an in silico strategy was employed to design and evaluate DNA Aptamers of varying lengths (30-mer, 40-mer, and 50-mer) for selective recognition of PIVKA-II. Aptamer structural stability, binding affinity, and specificity were systematically investigated using secondary structure prediction, molecular docking, and molecular dynamics simulations. Binding interactions were assessed at Pv6268 and Pv4n, representing distinct PIVKA-II binding sites, while Pv0 (prothrombin) was used as a non-target protein to evaluate crossreactivity. The 30-mer and 40-mer DNA Aptamers formed compact and conformationally stable structures and exhibited strong binding at the Pv4n sites with negligence crossreactivity toward Pv0. In contrast, the 50-mer DNA Aptamer displayed increased conformational flexibility, resulting in less selective in distinguishing between PIVKA-II protein variants and cross-reacted towards Pv0. These findings highlight the critical role of Aptamer conformational adaptability in achieving high disease specificity and provide a rational framework for the computational design of highly selective PIVKA-II-targeted Aptamers for hepatocellular carcinoma diagnostics..
Histopathological changes in the brain, kidney and liver tissues of type 2 diabetic neuropathy rats model
(2026-01)
Azman, Qistina Tihani Mohd
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, oxidative stress, and inflammation, leading to progressive damage across multiple organ systems. This study aimed to evaluate histopathological alterations in the brain, kidney, and liver tissues and to assess the protective effects of minocycline and gabapentin in a type 2 diabetic neuropathy (T2DM) rat model. Diabetes was experimentally induced, and animals were divided into five groups: normal control, diabetic control, minocycline-treated groups at low and high doses (40 and 80 mg/kg), and a gabapentin-treated group (100 mg/kg). Histopathological examinations of brain, kidney, and liver tissues were performed using hematoxylin and eosin (H&E) staining. Lesion severity was evaluated using a semi-quantitative scoring system (0 = no lesions, 1 = mild, 2 = moderate, and 3 = severe). Statistical analysis was conducted using one-way ANOVA followed by Tukey’s post hoc test. The diabetic control group exhibited severe histopathological abnormalities, including neuronal degeneration and demyelination in the brain, tubular and glomerular damage in the kidney, and vacuolar degeneration, congestion, and fatty changes in the liver. Treatment with minocycline significantly attenuated lesion severity in all examined organs in a dose-dependent manner, with the higher dose (80 mg/kg) demonstrating superior protective effects. In contrast, gabapentin treatment resulted in partial histological improvement, with persistent tissue damage observed. In conclusion, minocycline exerted significant dose-dependent protective effects against diabetes-induced histopathological damage in the brain, kidney, and liver. These findings suggest that minocycline may represent a promising therapeutic strategy for mitigating diabetes-related multi-organ complication.
Assessment of alpha-pinene on digestive vacuole pH in plasmodium falciparum
(2026-01)
Yu, Pua Cai
Malaria remains a life-threatening mosquito-borne infectious disease and continues to pose a major global health challenge, predominantly caused by Plasmodium falciparum and transmitted by Anopheles mosquitoes. The emergence of resistance to commonly used antimalarial drugs, including chloroquine and artemisinin, has reduced treatment efficacy. This highlights the need for alternative antimalarial compounds with novel targets. Alpha-pinene has been reported to exhibit antimalarial activity; however, its effect on the digestive vacuole (DV) of P. falciparum has not been fully characterized. The DV is an acidic organelle essential for haemoglobin degradation and haem detoxification, processes that are critical for parasite survival. Disruption of DV pH homeostasis represents an important target for antimalarial intervention. In this study, the antimalarial activity of α-pinene was evaluated against the chloroquine-sensitive P. falciparum 3D7 strain. The half-maximal inhibitory concentration (IC50) was determined at the ring stage using the Giemsa-stained thin blood smear method. α-Pinene demonstrated an IC50 value of 6.908 μM, indicating effective inhibition of parasite growth. The effect of α-pinene on DV pH was further assessed in the mature-stage parasite using flow cytometry following labelling with FITC-dextran as a pH-sensitive fluorescent probe. A concentration-dependent alkalisation of the DV pH was observed following treatment. The observed DV pH disruption suggests that α-pinene may interfere with DV acidification, potentially involving inhibition of the V-type H+-ATPase. The findings of this study demonstrate that α-pinene exhibits antimalarial activity and disrupts DV pH homeostasis in P. falciparum. These results support the potential of α-pinene as a promising candidate for further investigation in antimalarial drug development.
The study of menadione supplementation on giardia lamblia viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
(2026-01)
Ganeson, Phiriyanka A/P
Giardia lamblia is a microaerophilic protozoan parasite with distinct metabolic features that challenge the performance of conventional tetrazolium-based viability assays. The widely used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay often yields low signal intensity in G. lamblia cultures due to the parasite’s lack of functional mitochondria and reliance on non-mitochondrial redox systems, thereby limiting assay sensitivity and quantitative resolution. This study aimed to evaluate whether menadione supplementation could enhance the performance of the MTT viability assay for assessing G. lamblia trophozoite viability. Serially diluted G. lamblia trophozoites were cultured to establish decreasing confluence across microtiter plate wells and analysed by visual grading at different timepoints post-cell seeding. The establish plate were then used for the comparative study of conventional MTT assays with and without menadione supplementation. Cell viability was quantified based on optical density (OD) measurements. Assay performance was evaluated using Pearson’s correlation analysis, signal-to-background (S/B) ratio calculations, and limit of detection (LOD) analysis. The results demonstrated that an incubation period of 48 hours produced the most stable and reproducible cell confluence for both assay conditions. Linearity between cell seeding density and OD values was assessed using simple linear regression analysis. Both assays revealed the same linearity range. A statistically significant positive correlation was observed between cell seeding density and OD values for both the conventional MTT and MTT–menadione assays (p < 0.001). However, the standard MTT assay showed a stronger relationship (r = 0.839) compared to the MTT–menadione assay (r = 0.582). The S/B was also higher in MTT assay, compared to MTT–menadione assays. Menadione supplementation resulted in increased OD values at high cell confluence, indicating enhanced signal intensity. However, this increase in signal intensity did not lead to a corresponding improvement in LoD, suggesting inherent metabolic constraints of G. lamblia that limit detection sensitivity at low cell densities. In conclusion, the conventional MTT assay remains reliable for quantitative viability assessment, while the MTT–menadione assay offers improved signal clarity for comparative studies in G. lamblia in high cell confluence settings.
Effects of TAK-242 on inflammatory cytokines production in serum of mice immunized with BCG vaccine
(2026-01)
Xianhan, Peng
This study investigated the regulatory role of TLR4 signaling in BCG vaccine-induced immune responses using the specific inhibitor TAK-242. In a BALB/c mouse model, TLR4 inhibition did not consistently reduce levels of the pro-inflammatory cytokines TNF-α and IL-1β and even resulted in increased TNF-α post-BCG immunization, revealing complexity and compensation within the immune signaling network. Analysis of the humoral response revealed subtype-specific effects: TAK-242 selectively inhibited the Th1-dependent progressive increase in IgG2a, without significantly affecting IgG1 and IgG2b levels. These findings suggest that TLR4 signaling acts as a fine tuner for the quality of the adaptive immune response, particularly in shaping Th1 bias, rather than as an absolute trigger for immune activation. This study highlights the value of integrated antibody subtype analysis with innate immune markers for comprehensive vaccine mechanism assessment and provides experimental evidence for understanding the role of TLR signaling regulation in vaccine immunology.

Browse

Recent Submissions