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  1. Yaacob NS, Kaderi MA, Norazmi MN
    J Clin Immunol, 2009 Sep;29(5):595-602.
    PMID: 19472040 DOI: 10.1007/s10875-009-9300-1
    BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) have been implicated in immune regulation. We determined the transcriptional expression of the three isoforms, PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages, CD4- and CD8-positive lymphocytes in non-obese diabetic (NOD) mice at 5 and 10 weeks of age as well as at diabetic stage.

    RESULTS: Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARalpha but reduced levels of PPARgamma2, while PPARgamma1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARalpha in diabetic NOD mice and greatly reduced expression of PPARgamma2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARgamma1 in diabetic NOD mice but no difference in PPARalpha and PPARgamma2 expression was observed compared to NOR mice.

    CONCLUSION: The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.

  2. Yaacob NS, Kaderi MA, Norazmi MN
    J Clin Immunol, 2004 Mar;24(2):177-84.
    PMID: 15024185 DOI: 10.1023/B:JOCI.0000019783.61674.1d
    Type 1 diabetes is an autoimmune disease that results from the destruction of the insulin-producing pancreatic beta islet cells, probably via the influence of cytokines. However, direct correlation between the expression of selected cytokines by various immune cells at different time points during the progression of the disease has not yet been clearly demonstrated. In this study, we showed that the mRNA expression of the pro-inflammatory cytokines, TNF-alpha, IL-1 beta, IL-6, and GM-CSF, were increased while the anti-inflammatory cytokine, TGF-beta, decreased in the peritoneal macrophages of nonobese diabetic (NOD) mice. IL-6 expression however decreased when the mice became diabetic. Surprisingly the expression of IFN-gamma and IL-2 by splenic CD4+ cells were lower in 5-week-old NOD mice as compared to the nonobese diabetic resistant (NOR) control mice, but their expression was higher in older NOD mice. The expression of IL-4 and IL-10 decreased in splenic CD4-positive lymphocytes. Splenic CD8-positive lymphocytes expressed increased levels of IFN-gamma and IL-10 but the latter decreased sharply when diabetes occurred. The relevance of these findings to the pathogenesis of type 1 diabetes is discussed.
  3. Taher M, Mohamed Amiroudine MZ, Tengku Zakaria TM, Susanti D, Ichwan SJ, Kaderi MA, et al.
    PMID: 25873982 DOI: 10.1155/2015/740238
    Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.
  4. Engku Nasrullah Satiman EAF, Ahmad H, Ramzi AB, Abdul Wahab R, Kaderi MA, Wan Harun WHA, et al.
    J Oral Pathol Med, 2020 Oct;49(9):835-841.
    PMID: 32170981 DOI: 10.1111/jop.13014
    Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin, has been reported as an essential molecule in epithelial damage and host recognition of C albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C albicans such as adhesion, biofilm formation and filamentation properties. This review discusses the recent epidemiological burden of oral cancer and highlights the significance of the ECE1 gene and the ECE1 protein breakdown product, candidalysin in oral malignancy. The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.
  5. Ahmad A, Yassin WM, Rahman NAA, Leman WI, Rosla L, Paul M, et al.
    Malays J Med Sci, 2021 Feb;28(1):66-74.
    PMID: 33679222 DOI: 10.21315/mjms2021.28.1.9
    Background: Nasopharyngeal carcinoma (NPC) is the fifth most common cancer among Malaysians. While several studies have reported the trend of NPC in other states in Malaysia, no studies have reported the trend of NPC in Pahang state. This study was designed to report the number and distribution of newly diagnosed NPC cases in Pahang.

    Methods: NPC cases that were diagnosed between 2012 and 2017 in two referral hospitals in Pahang were traced. The crude incidence rate (CR) and age-standardised rate (ASR) were calculated to investigate the NPC incidence.

    Results: There were 143 new cases of NPC reported from the two hospitals. The mean age at diagnosis was 52.0 ± 13.7 years old. The majority of cases involved males (74.1%) with a male to female ratio of 2.9:1. Chinese males were found to have the highest incidence with a mean ASR of 4.7 per 100,000 population. Overall, the mean ASR for Pahang was 2.4 per 100,000 population for males and 0.9 per 100,000 population for females.

    Conclusion: The total number of NPC cases reveals an increasing trend from 2012 to 2014 and then a slightly decreasing trend from 2015 to 2017. The incidence of NPC in Pahang was intermediate in males and low in females.

  6. Benner A, Mansouri L, Rossi D, Majid A, Willander K, Parker A, et al.
    Haematologica, 2014 Aug;99(8):1285-91.
    PMID: 25082786 DOI: 10.3324/haematol.2013.101170
    A number of single nucleotide polymorphisms have been associated with disease predisposition in chronic lymphocytic leukemia. A single nucleotide polymorphism in the MDM2 promotor region, MDM2SNP309, was shown to soothe the p53 pathway. In the current study, we aimed to clarify the effect of the MDM2SNP309 on chronic lymphocytic leukemia characteristics and outcome. We performed a meta-analysis of data from 2598 individual patients from 10 different cohorts. Patients' data and genetic analysis for MDM2SNP309 genotype, immunoglobulin heavy chain variable region mutation status and fluorescence in situ hybridization results were collected. There were no differences in overall survival based on the polymorphism (log rank test, stratified by study cohort; P=0.76; GG genotype: cohort-adjusted median overall survival of 151 months; TG: 153 months; TT: 149 months). In a multivariable Cox proportional hazards regression analysis, advanced age, male sex and unmutated immunoglobulin heavy chain variable region genes were associated with inferior survival, but not the MDM2 genotype. The MDM2SNP309 is unlikely to influence disease characteristics and prognosis in chronic lymphocytic leukemia. Studies investigating the impact of individual single nucleotide polymorphisms on prognosis are often controversial. This may be due to selection bias and small sample size. A meta-analysis based on individual patient data provides a reasonable strategy for prognostic factor analyses in the case of small individual studies. Individual patient data-based meta-analysis can, therefore, be a powerful tool to assess genetic risk factors in the absence of large studies.
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