Browsing by Author "Asmah Hanim Hamdan, Ph.D"

Cardiovascular diseases are major contributor to morbidity and mortality worldwide. Atherosclerosis is a leading cause to cardiovascular diseases in addition to its pathogenic association with non-alcoholic fatty liver disease (NAFLD). Protection against atherosclerosis and NAFLD constitutes a global aim. Modern trend has emerged to reintroduce natural products such as honey for management of these metabolic epidemics because of the less side effects perhaps. In the present study, Trihoney was investigated for its anti-atherosclerotic and hepatoprotective effects in diet induced hypercholesterolemic rabbits model. Forty-eight male New Zealand white rabbits were randomly assigned to one of 6 groups. First group was fed only commercial rabbit diet, second group was fed commercial rabbit diet with 0.6g of Trihoney/kg/day, third group was fed 1% cholesterol diet, fourth and fifth groups were fed 1% cholesterol diet with 0.3 and 0.6 g of Trihoney/kg/day while the last group was fed 1% cholesterol diet plus 2mg of atorvastatin/kg/day. Experiment continues for 12 weeks duration. Blood samples were withdrawn before and after the experimental period. Aorta and liver were harvested and processed for homogenate and histopathological studies. In the first phase, Trihoney was investigated for its lipid lowering and anti-inflammatory effects through analysis of serum lipids [total cholesterol (TC), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), triglycerides (TG) and TC/HDL risk ratio] and by assay of serum pro-atherogenic inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)]. The results showed that Trihoney had significant lipid lowering and marked anti-inflammatory effects. In the second phase, Trihoney was assessed for antioxidant function by analysing serum and aorta homogenate for superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in addition to analysing serum for oxidised-LDL (Ox-LDL). Results showed that Trihoney exerted significant antioxidant effects systemically as well as locally in the aorta. In the third phase, Trihoney was investigated of its effects on the atherosclerotic plaques, inflammatory adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and on homocysteine. Results showed that Trihoney had significant anti-inflammatory and vascular protective functions. In the fourth phase, Trihoney was examined for hepatoprotective function against NAFLD through histopathological study and via assay of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (T. Bil.), alkaline phosphatase (ALP), fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). In addition to antioxidant assay of liver homogenate for SOD, GPx and MDA. Results showed that under status of sustained hypercholesterolemia, Trihoney was able to normalise hepatic function in NAFLD induced hypercholesterolemia, Trihoney showed no effect on fasting glucose, insulin and HOMA-IR, Trihoney exhibited significant antioxidant effect against hepatic oxidative stress and it was protective against progression of NAFLD to non-alcoholic steatohepatitis (NASH). Accordingly, Trihoney has a potential protective role against atherosclerosis and NAFLD through hypocholesterolemic, antioxidant and anti-inflammatory functions. Further studies may be needed to explore possible molecular mechanisms underlying those health beneficial properties of Trihoney.

Acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN) are the most common entities of myeloid neoplasms. In AML, among the most frequent genetic alterations that carries both diagnostic and prognostic values are mutations in Nucleophosmin 1 (NPM1) and FMS-like tyrosine kinase 3 (FLT3) genes. Nevertheless, their frequencies among AML patients in Kuantan, Pahang have not been studied. Additionally, published literatures on both of these mutations in MPN are scarce although they have been shown to confer MPN in animal model. This cross-sectional study therefore aimed to determine the proportion of FLT3-ITD, FLT3-D835 and NPM1 mutations among patients diagnosed with AML and MPN in Hospital Tengku Ampuan Afzan of Kuantan, Pahang from the year 2016 to 2019. A total of 56 cases were studied, of which 43 cases were AML and 13 cases MPN. Molecular methods employed were polymerase chain reaction-based assays for mutation detection, from the retrieved trephine biopsy tissue blocks. The mutation positivity was subsequently validated by Sanger DNA sequencing. Six of the 43 cases (14.0%) of AML were positive for FLT3-ITD and a similar proportion (6/43, 14.0%) were also positive for NPM1 mutations. FLT3-D835 mutation was identified in three of the AML cases (7.0%) while concurrent mutations of NPM1 and FLT3-ITD were seen in two of the mutation positive cases (4.7%). One of the 13 (7.7%) MPN cases was positive for FLT3-ITD. None of the MPNs cases were positive for either FLT-D835 or NPM1 mutations. When the mean haematological values were compared with the mutation status in AML cases, only the total white cell count was significantly higher with FLT3 mutations (p=0.001). In conclusion, the frequency of FLT3 mutations in the AML cases concurs with others, while the frequency of NPM1 mutations in our study was relatively lower as compared to other reports. The significance of the FLT3-ITD mutation positivity found in our series of MPN remains to be elucidated.

Colorectal cancer (CRC) is the second most common tumour in Malaysia. Universal screening for the identification of microsatellite instability/mismatch repair (MSI/MMR) status in CRC patients is recommended by several guidelines. The detection of MSI/MMR status in CRC patients is not only essential to identify Lynch Syndrome (LS), but it also has predictive and prognostic values. The study aimed to investigate the MMR and MSI status among CRC patients in Kuantan, Pahang as well as to assess the consistency between immunohistochemistry (IHC) and MSI analysis. Formalin-fixed paraffin-embedded (FFPE) tissue blocks of 123 CRC patients were retrieved for the years 2017-2018. For IHC and MSI analysis, EnVisionTM FLEX, Mini Kit, High PH, and MSI Analysis System 1.2 (Promega) were utilized, respectively. MSI analysis was performed on selected deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) cases. IHC detected 11.4% (14 out of 123) patients as dMMR and 88.6% (109 out of 123) as pMMR. MSI analysis identified 26% (13 out of 50) patients as MSI-H, 6% (3 out of 50) patients as MSI-L, and 64% (32 out of 50) patients as MSS. Both the IHC and MSI analysis showed perfect agreement (0.896, Kappa value) for the recognition of dMMR or MSI-H CRC patients while demonstrating only 4% (2 out of 50) discordant results. Almost all dMMR patients detected by IHC were recognized by MSI analysis as MSI-H except one. The significant prevalence of dMMR in current cohort support the recommendation that the assessment of MSI/MMR status should be addressed in CRC patients. The selection of the choice method may be based on the availability of the expertise and equipment. Since IHC is an affordable, a reproducible and readily available in most histopathological laboratories, it can be used as a primary screening test to detect MSI/MMR status in CRC patients.