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Inhibitory effects of Tualang Honey on experimental breast cancer in rats: a preliminary study

Kadir EA, Sulaiman SA, Yahya NK, Othman NH

Asian Pac J Cancer Prev, 2013;14(4):2249-54.
PMID: 23725121

The study was conducted to determine the effect of Malaysian jungle Tualang Honey (TH) on development of breast cancer induced by the carcinogen 7,12-dimethylbenz(α)anthracene (DMBA) in rats. Forty nulliparous female Sprague-Dawley rats were given 80 mg/kg DMBA then randomly divided into four groups: Group 1 served as a Control while Groups 2, 3 and 4 received 0.2, 1.0 or 2.0 g/kg bodyweight/day of TH, respectively, for 150 days. Results showed that breast cancers in the TH-treated groups had slower size increment and smaller mean tumor size (≤ 2 cm3) compared to Controls (≤ 8 cm3). The number of cancers developing in TH-treated groups was also significantly fewer (P<0.05). Histological grading showed majority of TH-treated group cancers to be of grade 1 and 2 compared to grade 3 in controls. There was an increasing trend of apoptotic index (AI) seen in TH-treated groups with increasing dosage of Tualang Honey, however, the mean AI values of all TH-treated groups were not significantly different from the Control value (p>0.05). In conclusion, Tualang Honey exerted positive modulation effects on DMBA-induced breast cancers in rats in this preliminary study.
Fulltext Correlation of Demographic and Clinical Characteristics with Rheumatoid Factor Seropositivity in Rheumatoid Arthritis Patients

Othman MA, Ghazali WS, Yahya NK, Wong KK

Malays J Med Sci, 2016 Nov;23(6):52-59.
PMID: 28090179 MyJurnal DOI: 10.21315/mjms2016.23.6.6

BACKGROUND: The rheumatoid factor (RF) blood test is the most commonly adopted test for the diagnosis of rheumatoid arthritis (RA). RA patients who are seropositive for RF might face a greater likelihood of developing more aggressive symptoms.
METHODS: Our goal was to study the demographic and clinical characteristics, as well as their correlation with RF seropositivity, among a series of 80 RA patients aged ≥ 18 years who attend Hospital Universiti Sains Malaysia (HUSM).
RESULTS: Of the 80 RA patients included in this study, 66 (82.5%) were female and 14 (17.5%) were male. No significant associations between RF seropositivity and demographic and/or clinical characteristics or other laboratory investigations were observed, including gender, morning stiffness, individual joint involvement (from multiple sites of the body), and erythrocyte sedimentation rate (ESR) measurement. However, a significant association between RF seropositivity and patients aged ≥ 50 was found (P = 0.032).
CONCLUSION: RF seropositivity was found to be more common in much older RA patients.
Fulltext Older age and diclofenac are associated with increased risk of upper gastrointestinal bleeding in gout patients

Wan Ghazali WS, Wan Zainudin WMKB, Yahya NK, Mohamed Ismail A, Wong KK

PeerJ, 2021;9:e11468.
PMID: 34055491 DOI: 10.7717/peerj.11468

Background: Gouty arthritis is a disease of global burden in which defective metabolism of uric acid causes arthritis. Gouty arthritis or medications used for its treatment may lead to uric acid-associated complications such as upper gastrointestinal bleeding (UGIB) and renal impairment.
Methods: In this cross-sectional study with retrospective record review, 403 established gouty arthritis patients were recruited to determine the incidence of UGIB and associated factors among gout patients who were on regular nonsteroidal anti-inflammatory drugs (NSAIDs).
Results: The mean age of the 403 gouty arthritis patients was 55.7 years old and the majority (n = 359/403; 89.1%) were male. The incidence of UGIB among gouty arthritis patients who were on NSAIDs was 7.2% (n = 29/403). Older age (p < 0.001), diclofenac medication (p = 0.003), pantoprazole medication (p = 0.003), end-stage renal failure (ESRF) (p = 0.007), smoking (p = 0.035), hypertension (p = 0.042) and creatinine (p = 0.045) were significant risk factors for UGIB among the gouty arthritis patients in univariable analysis. Older age (p = 0.001) and diclofenac medication (p < 0.001) remained significant risk factors for UGIB among the gouty arthritis patients in multivariable analysis.
Conclusions: Age and diclofenac were significantly associated with UGIB among patients with gouty arthritis on regular NSAIDs, indicating that these factors increased the risks of developing UGIB in gout patients. Hence, these high-risk groups of gouty arthritis patients should be routinely monitored to avoid the potential onset of UGIB. Our data also suggest that diclofenac should be prescribed for the shortest duration possible to minimize the risk of developing UGIB in gout patients.
Fulltext Anti-carbamylated protein antibodies in rheumatoid arthritis patients and their association with rheumatoid factor

Othman MA, Ghazali WSW, Hamid WZWA, Wong KK, Yahya NK

Saudi Med J, 2017 Sep;38(9):934-941.
PMID: 28889152 DOI: 10.15537/smj.2017.9.20841

OBJECTIVES: To evaluate levels of anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and to determine their association with serological parameters and disease activity. Methods: A cross-sectional study involving 105 multiethnic RA patients (48 rheumatoid factor [RF]-positive and 57 RF-negative patients) was conducted at Hospital Universiti Sains Malaysia, Kelantan, Malaysia, from January 2015 to February 2016. Fifty healthy controls (HCs) were included. C-reactive protein (CRP), RF, anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies were measured. A health assessment questionnaire (HAQ) was administered to the study participants and 28-joint Disease Activity Score (DAS28) were obtained. Results: The level of anti-CarP antibodies was significantly increased in the RA patients compared with HCs (p=0.042). The presence of anti-CarP antibodies was significantly associated with RF (p=0.019) and the HAQ (p=0.010). A significant association between the presence of anti-CarP antibodies and the DAS28 was not found (p=0.632). Conclusion: Our study provides further evidence that the level of anti-CarP antibodies is significantly elevated in RA patients.

Study site: Rheumatology clinic, Hospital Universiti Sains Malaysia
Fulltext The usefulness of endothelial cell adhesion molecules and anti-C1q antibody in monitoring systemic lupus erythematosus disease activity

Mahayidin H, Yahya NK, Wan Ghazali WS, Mohd Ismail A, Wan Ab Hamid WZ

Int Sch Res Notices, 2014;2014:275194.
PMID: 27355017 DOI: 10.1155/2014/275194

Objectives. The study was conducted to determine the correlation of ICAM-1, VCAM-1, and anti-C1q antibody levels with SLE disease activity index (SLEDAI) and standard SLE disease activity immunological markers (anti-dsDNA and sera C3 and C4). Study Design. This was a cross-sectional study. Materials and Methods. Blood samples were obtained from 95 SLE patients (45 active SLE and 50 nonactive SLE) and 50 controls. The subjects were assessed using SLEDAI and score of more than five is determined as having active SLE. The sera were tested for serum ICAM-1, VCAM-1, and anti-C1q (ELISA), anti-dsDNA (CLIFT), serum C3, and serum C4 (immunonephelometry). Results. Anti-dsDNA and anti-C1q antibody showed good positive correlations with SLEDAI (r = 0.529, P < 0.001 and r = 0.559, P < 0.001, resp.). VCAM-1 and sera C3 and C4 showed fair correlation with SLEDAI (r = 0.294, P = 0.004; r = -0.312, P = 0.002; and r = -0.382, P < 0.001, resp.). ICAM-1 level showed no significant correlation with SLEDAI (P = 0.062). There were significant correlations of VCAM-1 and anti-C1q antibody with anti-dsDNA (r = 0.226, P = 0.006 and r = 0.511, P < 0.001, resp.). VCAM-1 showed poor inverse correlation with serum C3 (r = -0.183, P = 0.028) and fair inverse correlation with serum C4 (r = -0.251, P = 0.002). Anti-C1q antibody demonstrated fair inverse correlation with both sera C3 and C4 (r = -0.420, P ≤ 0.001 and r = -0.398, P < 0.001, resp.). However, ICAM-1 showed no significant correlation with anti-dsDNA and sera C3 and C4 (P = 0.259, P = 0.626 and P = 0.338, resp.). Conclusions. The serum levels of anti-C1q antibody in SLE patients showed the best correlation with the SLEDAI and standard immunological tests for SLE disease activity. These data support that anti-C1q antibody is a useful marker for monitoring SLE global disease activity. The potential of VCAM-1 needs further confirmation.
Study site: Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, and Hospital Raja Perempuan Zainab II (HRPZ II), Kota Bharu, Kelantan, Malaysia
Towards understanding the role of nanomedicine in targeting TNFR2 in rheumatoid arthritis

Lambuk F, Nordin NA, Mussa A, Lambuk L, Ahmad S, Hassan R, et al.

Immunology, 2024 Aug 27.
PMID: 39191474 DOI: 10.1111/imm.13855

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium and progressive joint destruction which significantly affects both quality of life and socioeconomic status. Admittedly, various treatments are available, but they are usually accompanied by various side effects, from mild to severe, and potentially with adverse events. Tumour necrosis factor-alpha (TNF-α) plays a crucial role in the pathophysiology of RA. It promotes inflammatory, apoptosis and necroptosis via TNF receptor-1 (TNFR1) but elicit anti-inflammatory effects via TNFR2. Herein, targeting TNFR2 has gained attention in RA studies. Understanding the role of nanomedicine in modulating TNFR2 signalling may be the instrument in development of RA therapies. Nanotechnology has made a significant progress in treating various conditions of diseases since its inception. Due to this, nanomedicine has emerged as a promising therapeutics approach for RA. Recent studies have demonstrated the potential of nanomedicine in RA theranostics, combining therapy and diagnostics for improved treatment outcomes. Owing to the challenges and advancements in the field of nanotechnology, nanoparticles are seen as an applicable candidate in the treatment of RA. In this review, we provide an overview of the role of nanomedicine in targeting TNFR2 for the treatment of RA and highlight the limitations of current therapies as well as the potential of nanocarriers with controlled drug release and active targeting abilities.
Fulltext Evaluation of endothelial cell adhesion molecules and anti-C1q antibody in discriminating between active and non-active systemic lupus erythematosus

Mahayidin H, Yahya NK, Wan Ghazali WS, Mohd Ismail A, Wan Ab Hamid WZ

Malays J Med Sci, 2016 May;23(3):22-31.
PMID: 27418866

BACKGROUND: Detecting the active state of systemic lupus erythematosus (SLE) is important but challenging. This study aimed to determine the diagnostic accuracy of serum endothelial cell adhesion molecules (ICAM-1 and VCAM-1) and anti-C1q antibody in discriminating between active and non-active SLE.
METHODS: Using SELENA-SLE disease activity index (SLEDAI), 95 SLE patients (45 active and 50 non-active) were assessed. A score above five was considered indicative of active SLE. The blood samples were tested for serum ICAM-1, VCAM-1 and anti-C1q antibody using enzyme-linked immunosorbent assay (ELISA).
RESULTS: The levels of serum VCAM-1 and anti-C1q antibody were significantly higher in active SLE patients. Both VCAM-1 and anti-C1q were able to discriminate between active and non-active SLE (p-value < 0.001 and 0.005, respectively). From the receiver operating characteristic curves (ROCs) constructed, the optimal cut-off values for VCAM-1 and anti-C1q antibody in discriminating between active and non-active SLE were 30.5 ng/mL (69.0% sensitivity, 60.0% specificity, PPV 58.5%, NPV 66.7%) and 7.86 U/mL (75.6% sensitivity, 80% specificity, PPV 77.3%, NPV 78.4%), respectively. However, serum ICAM-1 level was unable to discriminate between the two groups (p-value = 0.193).
CONCLUSION: Anti-C1q antibody demonstrated the best diagnostic accuracy in discriminating between active and non-active SLE patients.
KEYWORDS: anti-C1q antibody; cell adhesion molecules; intercellular adhesion molecule-1 (ICAM-1); systemic lupus erythematosus; vascular cell adhesion molecule-1 (VCAM-1)
Fulltext Phylogeography of the Sunda pangolin, Manis javanica: Implications for taxonomy, conservation management and wildlife forensics

Sitam FT, Salgado-Lynn M, Denel A, Panjang E, McEwing R, Lightson A, et al.

Ecol Evol, 2023 Aug;13(8):e10373.
PMID: 37593756 DOI: 10.1002/ece3.10373

The Sunda pangolin (Manis javanica) is the most widely distributed Asian pangolin species, occurring across much of Southeast Asia and in southern China. It is classified as Critically Endangered and is one of the most trafficked mammals in the world, which not only negatively impacts wild Sunda pangolin populations but also poses a potential disease risk to other species, including humans and livestock. Here, we aimed to investigate the species' phylogeography across its distribution to improve our understanding of the species' evolutionary history, elucidate any taxonomic uncertainties and enhance the species' conservation genetic management and potential wildlife forensics applications. We sequenced mtDNA genomes from 23 wild Sunda pangolins of known provenance originating from Malaysia to fill sampling gaps in previous studies, particularly in Borneo. To conduct phylogenetic and population genetic analyses of Sunda pangolins across their range, we integrated these newly generated mitochondrial genomes with previously generated mtDNA and nuclear DNA data sets (RAD-seq SNP data). We identified an evolutionarily distinct mtDNA lineage in north Borneo, estimated to be ~1.6 million years divergent from lineages in west/south Borneo and the mainland, comparable to the divergence time from the Palawan pangolin. There appeared to be mitonuclear discordance, with no apparent genetic structure across Borneo based on analysis of nuclear SNPs. These findings are consistent with the 'out of Borneo hypothesis', whereby Sunda pangolins diversified in Borneo before subsequently migrating throughout Sundaland, and/or a secondary contact scenario between mainland and Borneo. We have elucidated possible taxonomic issues in the Sunda/Palawan pangolin complex and highlight the critical need for additional georeferenced samples to accurately apportion its range-wide genetic variation into appropriate taxonomic and conservation units. Additionally, these data have improved forensic identification testing involving these species and permit the implementation of geographic provenance testing in some scenarios.