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- PublicationAssessment of cytokine secretions by monocytes in the presence of synovial fluid-derived exosomes(2025-01)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
- PublicationThe effect of tlr4 agonist (crx-527) on il-10 production in mice immunized with bcg-msp-1c(2025-01)Malaria, caused by the Plasmodium parasite, continues to be a significant global health burden, particularly in regions with limited access to healthcare. Current malaria vaccines face challenges of suboptimal efficacy and logistical barriers for widespread implementation. One promising antigen for malaria vaccine development is the C-terminal region of merozoite surface protein 1 (MSP-1C), a conserved fragment of MSP-1, the major surface protein of Plasmodium merozoites, which is essential for red blood cell invasion and evasion of host immune responses. This study evaluates the impact of the Toll-like receptor 4 (TLR4) agonist CRX-527 on IL-10 production in mice immunized with the BCG-MSP-1C vaccine, developed in our laboratory by cloning the MSP-1C antigen with the Bacillus Calmette–Guérin (BCG) vaccine, which is primarily used for tuberculosis (TB) prevention. Treatment groups included PBS-T80, LPS, BCG, and BCG-MSP-1C. The results revealed a significant enhancement of IL-10 production across all groups in both liver and lymph node supernatant samples in the presence of CRX-527. Among these, the BCG-MSP-1C group exhibited the highest IL-10 levels, followed by the BCG, LPS, and PBS-T80 groups. IL-10, an anti-inflammatory cytokine, plays a pivotal role in regulating the immune response, ensuring controlled infection management while minimizing tissue damage. These findings highlight CRX-527’s potential as an effective immune-modulatory adjuvant for malaria vaccine strategies. The incorporation of CRX-527 with the BCG-MSP-1C vaccine offers a dual immunization approach, enabling protection against both malaria and tuberculosis with a single immunization. This strategy could significantly reduce the burden of multiple vaccine doses and improve immunization coverage in resource-limited settings. The study underscores the potential of CRX-527 to enhance vaccine efficacy and promote long-term immunity, supporting its role in advancing cost-effective, dual-purpose vaccine solutions for endemic regions
- PublicationDetermination of total immunoglobulin g and immunoglobulin g subclass response against sars-cov-2 omicron variant in pfizer and sinovac vaccinated serum samples(2025-01)The COVID-19 pandemic, caused by the highly transmissible SARS-CoV-2 virus, continues to pose significant global health challenges. The emergence of variants such as Omicron has raised concerns regarding immune escape, waning immunity, and the long-term effectiveness of COVID-19 vaccines. While vaccination remains the most effective strategy in mitigating severe disease and transmission, differences in immune responses elicited by various vaccine platforms necessitate further investigation. This study aimed to evaluate the humoral immune response, focusing on total Immunoglobulin G (IgG) levels and IgG subclasses (IgG1 and IgG4), in individuals vaccinated with Pfizer-BioNTech (BNT162b2) and Sinovac (CoronaVac) vaccines. A total of 14 participants were recruited, with seven receiving Pfizer and seven receiving Sinovac. Serum samples were collected at six critical time points: pre-vaccination, post-first dose, two weeks after the second dose, and post-booster doses at two, 26, and 52 weeks. An indirect enzyme-linked immunosorbent assay (ELISA) was employed to quantify spike-specific IgG responses. The results demonstrated a significant increase in total IgG levels over time in both vaccine groups (p < 0.0001). Sinovac recipients exhibited higher total IgG levels (predicted mean: 1.984) compared to Pfizer recipients (predicted mean: 1.442). IgG1 levels remained comparable between both groups across all time points (p > 0.05), with Sinovac showing a transiently higher IgG1 response at two- and 26-weeks post-booster. In contrast, IgG4 levels significantly increased in Pfizer recipients at later booster time points (26 and 52 weeks, p < 0.05), whereas Sinovac elicited a less pronounced IgG4 response. These findings suggest that Sinovac induces a stronger early total IgG response, while Pfizer leads to a more pronounced IgG4 response after booster doses. The distinct patterns of IgG subclass distribution may influence long-term immunity and immune regulation following vaccination. Understanding these differential immune responses is essential for optimizing booster strategies, refining vaccine policies, and ensuring prolonged protection against emerging SARS-CoV-2 variants
- PublicationEffects of different types of exercise intensities on immune responses, bone metabolism markers, antioxidant status and selected physiological parameters in physically inactive adults(2025-08)High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) was proven to enhance general fitness and health in healthy individuals. However, to date, studies on the effects of HIIT and MICT on immune responses, bone metabolism markers and antioxidant status in physically inactive adults are still limited. Therefore, the study was carried out. Thirty-six physically inactive male and female adults, aged 18-35 years were recruited and randomly assigned to HIIT, MICT or control groups with 12 participants per group (n=12). Participants in the HIIT group performed 2 sets of 6-8 repetitions of running at 85- 95% of HRmax on a motorised treadmill for 30 seconds, 3 times per week for 8 weeks. Participants in the MICT group performed 30 min of running on a motorised treadmill at 55-70% of HRmax, 3 times per week for 8 weeks. Participants in the control group did not engage in any exercise training throughout the intervention period. Anthropometric measurements, maximum oxygen consumption (VO2max), Wingate anaerobic capacity, isokinetic muscular strength and power, blood (for the analysis of whole blood count, calcium, alkaline phosphatase, osteocalcin, carboxy-terminal telopeptide of type-1 collagen and total antioxidant status) and saliva samples (for analysis of saliva flow rate and salivary lysozyme concentration and secretion rate) were taken prior to and following 8 weeks of training intervention. Results indicated that both HIIT and MICT significantly increased salivary lysozyme concentration and dominant knee extension average power at 300º.s-1 compared to pre-test measurement (p<0.05), though no significant differences were observed between groups (p>0.05). VO2max improved significantly in the HIIT group (p<0.05), whereas total monocyte count and serum ALP concentration were significantly higher in the MICT group compared to controls post-intervention (p<0.05). A significant reduction in anaerobic and peak power were noted in both groups at post-test compared to pre-test measurements (p<0.05). No significant differences across groups and time were found in the other measure parameters. In conclusion, both HIIT and MICT enhance specific immune response markers and isokinetic muscular power in physically inactive adults. However, HIIT demonstrated superior improvements in cardiovascular fitness and MICT was better at enhancing bone metabolism marker. These findings suggest that practitioners should consider incorporating HIIT into exercise regimens as a time- efficient alternative that may appeal to those with perceived time constrains for exercise while providing effective health benefits.
- PublicationCardioprotective effects of bunga kantan (etlingera elatior) in hypercholesterolaemic myocardial infarction sprague dawley rats(2025-01)Cardiovascular diseases (CVDs), especially myocardial infarction (MI), remain a global health challenge with high mortality rates. Despite advancements in surgical and pharmacological interventions, the prevalence of MI continues to rise, often linked to risk factors such as hypercholesterolaemia. Alternative therapies utilising natural compounds with cardioprotective properties offer a promising alternative for addressing these limitations. This study investigates the potential of Etlingera elatior aqueous extract (EEAE) as a preventive treatment against hypercholesterolaemia-induced MI. The research employed a high-cholesterol diet (HCD) to induce hypercholesterolaemia in male Sprague-Dawley rats, followed by isoprenaline administration to induce MI. Rats treated with EEAE at 1000 mg/kg were evaluated over 12 weeks. Parameters, including blood pressure and cholesterol levels, were taken. Histopathological analyses were conducted to observe structural improvements in the myocardium. Results demonstrated that EEAE had no significant effect in lowering cholesterol levels and blood pressure but showed capability in preserving cardiac integrity. EEAE-treated groups exhibited enhanced histological recovery compared to untreated controls. These findings suggest that EEAE holds potential as a natural therapeutic agent for preventing MI in hypercholesterolemic conditions. Further research is needed to explore its mechanisms and applicability in clinical settings
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- PublicationCharacterisation And Formulation Of Topical Methyl Salicylate Patches: Effect Of Solvents On Adhesion And Drug Permeation(2023-01)Topical methyl salicylate (MS) patch is popular for pain management. The skin permeation profile of MS is important for formulation design but limited studies were conducted. This project aims to investigate the effect of solvents on the characteristics of patches, drug release and permeation of MS. In this project, suitable solvents were first selected for the patch formulation. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was utilised to scan the stratum corneum (SC) sheets treated with solvents and MS. Next, in vitro permeation studies were carried out with 10%v/v of MS in solvents. After that, patches containing 5%w/w of solvents and/or 10%w/w of MS were prepared with Durabond PC 1879A (8%w/w), Nikasol TS-620 (7%w/w), carboxymethyl cellulose (3.5%w/w) and polyvinyl pyrrolidone (3%w/w). Next, the patches formed were subjected to physiochemical characterisation tests, including ATR-FTIR spectroscopy, tackiness test using stainless-steel probe, peel strength test with porcine ear skin, swelling test, in vitro drug release and skin permeation studies. In in vitro permeation studies, MS in propylene glycol (PG) in drug solution displayed the highest skin permeation of MS and followed by Plurol® oleique (PLU), Labrasol® (LA), Transcutol® (TRC), Maisine® (MAI) and isopropyl myristate (IPM) at 24 h.
- ItemORAL BIOA V AILABILITY ENHANCEMENT OF POORLY SOLUBLE AND POORLY PERMEABLE DRUGS USING SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEMS AND THE EFFECT OF PIPERINE(2010-01)There are approximately 40% of new drug molecules discovered and some drug molecules that are available in the market, having poor bioavailability due to poor solubility and/or poor permeability. The present study aimed at formulating a selfmicroemulsifying drug delivery system (SMEDDS) using two BCS class IV drugs, namely sulpiride and norfloxacin. Sulpiride is a P-gp substrate and norfloxacin is a substrate of MRP2, BCRP and an unknown efflux pump. From the solubility studies of drugs in various oils, surfactants and co-surfactants, oleic acid, Tween 80 and propylene glycol were chosen to prepare SMEDDS formulations. Two formulations were chosen for further study based on droplet size and solubility. The first formulation consisted of 4.76% w/w of oleic acid, 63.49% w/w of Tween 80 and 31.7 5% w/w of propylene glycol, with a mean droplet diameter of 9.27 nrn and drug solubility of 22 mg/1000 mg for sulpiride, 9.57 nrn and 17.33 mg/1000 mg for norfloxacin respectively. The other formulation consisted of 17.71% w/w of oleic acid, 55.14% w/w of Tween 80 and 27.15% w/w ofpropylene glycol, with a mean droplet diameter of 85 nrn and drug solubility of 32 mg/1 000 mg for sulpiride, 92 nrn and 27.53 mg/1000 mg for norfloxacin. !socratic HPLC- fluorescence methods were developed and validated for the determination of sulpiride and norfloxacin in rat intestinal perfusates and rabbit plasma separately. The in situ permeability experiment was performed on three intestinal segments, duodenum, jejunum and ileum in rats using single-pass perfusion technique. The SMEDDS formulation and micellar solution exhibited significant increase in the effective permeability XXXIX coefficient of the drug across all the three intestinal segments compared with drug solution for the two drugs. There was no significant difference in the effective permeability coefficients values between SMEDDS formulation and micellar solution for both drugs. When the effect of droplet sizes on jejunum permeability was studied, it was found that there was no significant difference in permeability coefficients with droplet sizes of less than 100 nm. From the in vivo bioavailability study performed in rabbits, it was found that there was a significant decrease in the T max and significant increase in the Cmax and AUC of the SMEDDS formulations when compared with Dogmatil®/Norfloxin® respectively. On the other hand, the rate and extent of absorption of sulpiride/norfloxacin were not significantly affected, when the droplet sizes of less than 100 nm were compared. When the effect of dietary spice piperine on the oral bioavailability of sulpiride/norfloxacin suspension and SMEDDS formulations was evaluated, it was found that concomitant administration of both the drugs with piperine in suspension and SMEDDS formulations significantly enhanced the oral bioavailability of these two drugs. Concomitant administration of piperine with SMEDDS formulation further increased the bioavailability of the drugs. Hence, SMEDDS can be used to increase the bioavailability of poorly soluble and poorly permeable drugs.
- ItemPENGHASILAN SEBATIAN AKTIF BERSIFAT ANTIBIOTIK DARIP ADA BAKTERIA MARIN PSEUDOMONAS DOUDOROFFI ABK37-MM(2003-07)A total of 450 bacterial and 7 fungal isolates were obtained from seawater, marine mud, l:· ~beach sand, floating material and marine macroorganisms collected from 11 sampling F sites around the Penang Island. These marine microorganisms isolates were screened for ·the production of antimicrobially active compound. From 450 bacterial isolates, 71.1% . were pigmented and sample from marine mud produced the highest marine bacterial isolates by 55.6% compared to other samples. Screening for the production of antimicrobial active compound from these bacterial isolates was performed by streaking and submerged culture fermentation techniques using yeast extract medium with half strength artificial seawater produced 3.3% and 47.1% positive isolates respectively, with various strength of antimicrobial activities. From these 47.1% marine bacterial isolates, sample from marine mud and yellow or yellowish pigmented isolates produced the highest potential isolates by 73.6% and 66.0%, respectively. Of the 47.1%, 87.3% isolates produced antibacterial compound, 19.3% isolates produced antifungal compound and 6.1% isolates produced antiyeast compound. Despite this, only 1.9% marine bacterial isolates showed antimicrobial activities against all the 8 test microorganisms. One potential marine bacterial isolate which produced the highest antibiotically active compound was chosen for the optimization of medium and cultural conditions in a shake XX!l nask system and was then identified as Pseudomonas duodoroffi ABK37-MM. The optimized medium for the production of antibiotically active compound against the test bacteria, Staphylococcus aureus was 1/8 diluted yeast extract medium ~~th half strength artificial seawater. The optimized medium compositions (%; w/v) were 0.06 maltose, . 0.06 yeast ext-act, 0.145 malt extract and 0.4 L-histidine. The optimized artificial ,. seawater compositions (%; w/v) were 1.8 NaCl , 0.5 MgCb.6H20, 0.1 CaCb,2H20, 0.1 r,KCI, 0.1 KBr, 0.2 Na2S04 and 0.05 NaHC03. The optimized cultural conditions for the ·production of antibiotically active compound were at an initial medium pH of 7.4, agitation rate of 140 rpm, incubation at room temperature (30±2°C), inoculum size of 6% and the volume of medium to the volume of flask ratio at 0.5. The production of antibiotically active compound increased by 37.0% with 14.3% faster than before optimization in a shake flask system .. Medium compositions, buffer concentration and a few physical parameters were reoptimized in the tubular air lift fermenter. The optimized medium (%; w/v) were 0.08 maltose, 0.08 yeast extract, 0.145 malt extract and 0.4 Lhistidine with 0.1 NaHC03. The optimized physical parameters were 1.5 vvm rate of aeration, inoculum size of 8% and the volume of medium to the volume of fermenter ratio of 0.75. Optimization at the fermenter level increased the production of antibiotically active compound by 26.0% at the same production time after optimization at the shake flask level, that was at 144 hours of cultivation. In general, there was an increase of about 72.6% in the production of antibiotically compound after optimization at a fermenter level compared to shake flask system. XX Ill Partial purification of the antibiotically active compound with sephadex G-1 00 gel filtration chromatography produced 9.2 folds of purity with specific antibiotically active compound of 1148.2 U/mg protein. Determination of molecular weigh!_ was done using SDS-PAGE and was estimated about 39 kD compared to known low molecular weight protein. Determination of protein compound and reducing sugar in the compound were 4.9 mg/ml and 0.02 mg/ml, respectively. The antibiotically active compound was found stable at and below of room temperature (30±2°C) and was fully deactivated at the temperature of 40°C. This compound was also found stable at pH range of 6 to 8 and fully deactivated by proteolytic enzyme suggesting that the major part of the compound was protein or protein moiety. TEM studies on the effects of the antibacterial compound on the test bacterial cell, Staphylococcus aureus revealed a chain reaction that occurred at the cell wall and cell membrane leading to cell lysis compared to untreated cell. The frequency and magnitude of the cell wall and cell membrane bleb bing and fragmentation of the test bacterial cell increased with the prolonged of exposure time to antibacterial compound, and it seems to produced pores in the bilayer cell wall leading to cell lysis.
- ItemEnhanced Image Processing Techniques Based On Technical Challenges Of Mammogram Image Characteristics(Universiti Sains Malaysia, 2010-04)Breast cancer is the leading type of cancer in Malaysia. More than 30% of total cancer case reported among women in Malaysia is made up of breast cancer. At the moment, one of the best known techniques used for breast cancer detection is mammography. Unfortunately, the image produced through mammography is normally noisy and low in contrast making detection of early signs of breast cancer (i.e. microcalcification and mass) difficult. Therefore, a lot of studies have been conducted to develop image processing techniques which would help in the detection of these early signs. However, most of these techniques were developed without a thorough study upon the mammogram image technical characteristics. Hence, an image which has been enhanced from one aspect may end up worst from another aspect. In this study, new image processing techniques have been developed based on findings which have been gathered from characterization of mammogram images. The characterization process covered the analysis of grey level distribution, noise, edge and texture. Detailed understanding of these characteristics, provide a solid basis for the development of new image processing techniques in this study. The new techniques brought forth through this study include contrast enhancement (i.e. Moving Contrast Sweep), noise suppression (i.e. Mean Approximation Adaptive Wiener Filter) and segmentation algorithm (i.e. Mean Median Crossing Segmentation). In addition to that, a new edge detection algorithm (i.e. Delta Variance Edge Detection) has also been developed to assist in microcalcification detection. Furthermore, a new classification system which is based on texture characteristic has also been developed for mass detection. Based on the analysis, it has been found that the Mean Approximation Adaptive Wiener Filter and Delta Variance Edge Detection techniques perform better than their predecessor. The performance of Mean Median Crossing Segmentation and Moving Contrast Sweep techniques is equivalent to existing techniques but they can be implemented through a more practical approach. The mass detection technique through statistical texture analysis demonstrates a lot of potential but still has room for improvement. It is hoped that, the new image processing techniques developed through solid understanding of mammogram image characteristic in this study could provide a strong foundation for the development of medical imaging applications in the future.
- ItemThe Sigficance of spatial factors in influencing the price of heritage properties in George Town, Penang.(2010)The aim of this research is to determine the significance of selected spatial factors and the influence of these spatial factors on heritage property prices in George Town 1. Spatial factors related to location, neighbourhood ·and local amenities such as transportation points, highway, shopping centre and school are tested in this research. Hedonic regression analysis is used to study the relationship between spatial factors and heritage property price in George Town 1. A total of 231 heritage property transaction records from year 1998 to 2004 are used in this analysis. The empirical result shows that spatial factor has significant influence on heritage property prices. 'Ferry route', 'shopping centre' and 'primary and secondary school' are three significant factors influencing heritage property prices in George Town 1. To further verify the significance of the above spatial factors, a spatial autocorrelation analysis is used for the second test. The analysis result indicates that property prices in George Town 1 are positive spatial autocorrelated. The positive spatial autocorrelated transaction prices in George Town reflect that property prices in George Town tend to depend on its neighbour. A geo-statistical method called Kriging is then used to verify the dependency of heritage property prices on its neighbours. A comparison between the predicted prices obtained from the Kriging map with actual transaction prices found that the predicted prices are reasonably close to the actual prices. As the Kriging method uses neighbouring properties prices to predict prices, the findings indicate that spatial factors especially neighbourhood has an influence on heritage property prices in George Town.