The effect of somatic mutations in mitochondrial DNA on the survival of patients with primary brain tumors.

AIM: To assess the presence of mitochondrial (mt) DNA somatic mutations, determine the relationship between clinicopathological characteristics and mutations, and assess the survival outcomes in Malay patients with primary brain tumors. METHODS: The study enrolled 54 patients with primary brain tumors. DNA extracted from paired tissue and blood samples was subjected to Sanger sequencing to identify alterations in the entire mtDNA. The associations between clinicopathological characteristics and mutations were evaluated. Cox-regression multivariate analysis was conducted to identify factors significantly associated with survival, and Kaplan-Meier analysis was used to compare the survival of patients with and without mutations. RESULTS: Overall, 29.6% of the patients harbored 19 somatic mutations distributed across 15 loci within the mtDNA. Notably, 36.8% of these mutations were not previously documented in MITOMAP. One newly identified mutation caused a frameshift in the ATPase6 gene, resulting in a premature stop codon. Three mutations were classified as deleterious in the MitImpact2 database. Overall, 1097 mtDNA polymorphisms were identified across 331 different locations. Patients with mutations exhibited significantly shorter survival than patients without mutations. CONCLUSIONS: mtDNA mutations negatively affected the survival outcomes of Malaysian patients with primary brain tumors. However, studies with larger samples are needed to confirm the association between mutation burden and survival rates.

Immunohistochemical expression of apolipoprotein B and 4-hydroxynonenal proteins in colorectal carcinoma patients: a retrospective study.

AIM: To assess the association of the expression of apolipoprotein B (apoB) and 4-hydroxynonenal (4HNE) with the clinicopathological data of patients with colorectal cancer (CRC). METHODS: We obtained 80 CRC histopathological specimens sent to the Pathology Laboratory of Hospital Universiti Sains Malaysia from 2015 to 2019. Data on demographic factors, body mass index (BMI), and clinicopathological characteristics were also collected. Formalin-fixed paraffin-embedded tissues were stained by using an optimized immunohistochemical protocol. RESULTS: Patients were mostly older than 50 years, male, Malay, and overweight or obese. A high apoB expression was observed in 87.5% CRC samples (70/80), while a high 4HNE expression was observed in only 17.5% (14/80) of CRCs. The expression of apoB was significantly associated with the sigmoid and rectosigmoid tumor sites (p =0.001) and tumor size 3-5 cm (p =0.005). 4HNE expression was significantly associated with tumor size 3-5 cm (p =0.045). Other variables were not significantly associated with the expression of either marker. CONCLUSION: ApoB and 4HNE proteins may play a role in promoting CRC carcinogenesis.

Disoriented collagen fibers and disorganized, fibrotic orbicularis oris muscle fiber with mitochondrial myopathy in non-syndromic cleft lip.

OBJECTIVE: This study aims to explore and compare the histopathology of upper cleft lip tissue in order to identify the abnormalities and orientation of muscle and collagen fibers in patients affected with non-syndromic cleft lip with or without cleft palate (NSCL±P) and normal controls. MATERIALS AND METHODS: Eight fresh lip tissues of consented patients with NSCL±P and two controls were fixed and stained with hematoxylin and eosin (H&E), Masson's trichrome (MT), and modified Gomori trichrome techniques. The images were captured and examined using imaging cellSens software (Olympus, Tokyo, Japan) and Mirax Scan (Carl Zeiss, Germany). The H&E stained tissues were analysed for muscle fiber size using image processing program (imageJ, USA). Histopathological appearance of epidermal and dermal layers including collagen orientation, as well as muscle fibers abnormalities were observed. RESULTS: Tissues stained with H&E exhibit pseudoepitheliomatous hyperplasia, epidermal and sebaceous glands hyperplasia. Morphometric analysis of muscle fibers showed the diameter was between 6.912 and 10.246 µm. Collagen fibers were densely packed in cleft tissue, but muscle fibers were sparse in MT stain. Modified Gomori trichrome stain revealed hypoplastic muscle with fibrosis, including ragged red fibers. CONCLUSION: Disoriented collagen fibers, significant sparse and disorganized orbicularis oris muscle fibers with classical myopathic appearances proved that cleft tissue had abnormal histology findings. These findings further support the mechanism of collagen and muscle fibers during embryonic development that causing cleft formation.

Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy

Abstract Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson's Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.

Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis.

Complete Freund's adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats' right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.

Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia.

BACKGROUND: Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). METHODS: A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. RESULTS: Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. CONCLUSION: The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

Prevalence of Cancers of Female Organs among Patients with Diabetes Type 2 in Kelantan, Malaysia: Observations over an 11 Year Period and Strategies to Reduce the Incidence.

INTRODUCTION: Kelantan is one of the states in Malaysia which has a high prevalence of type 2 diabetes (DM2). Other than with endometrial carcinoma, the association of DM2 with particular female cancers is not known. OBJECTIVE: To determine the proportion of breast, cervical, ovarian and endometrial cancers among females with DM2 diagnosed in Hospital Universiti Sains Malaysia (HUSM) over an 11 year period. MATERIALS AND METHODS: All histologically confirmed cases of breast, endometrial, cervical and ovarian carcinomas admitted to the Hospital were included in the study. The patient diabetic status was traced from the hospital medical records. RESULTS: There was a total of 860 cases of breast, cervical, ovarian and endometrial carcinomas over this period. Breast carcinoma was the commonest, accounting for 437/860 (50.8%) followed by cervix, 159/860 (18.5%), ovarian, 143/860 (16.6%) and endometrial carcinomas, 121/860 (14.1%). Out of these, 228/860 (26.5%) were confirmed diabetics. Endometrial carcinoma patients showed the highest proportion being diabetics, 42.1% (51/121), followed by ovarian cancer, 25.9% (37/143), breast carcinoma, 23.6% (103/437) and cervical cancer 23.3% (37/159). CONCLUSIONS: There is a significant proportion of DM2 among women with these four cancers, endometrial carcinoma being the highest followed by ovarian, breast and cervical carcinoma. The rising trend of these four cancers is in tandem with an increasing trend of DM2 in the community. In populations where diabetes is prevalent, screening for epithelial cancers should be rigourous. Diabetic clinics should include screening for these cancers among their female patients and gynecology clinics should screen the women they treat for their diabetes status.

Association of colorectal carcinoma with metabolic diseases; experience with 138 cases from Kelantan, Malaysia.

OBJECTIVE: Kelantan in Malaysia has a high prevalence of diabetes and colorectal cancer is also on the rise. This study is to determine the association of metabolic diseases, particularly diabetes type 2 [DM2] and hypertension, with colorectal cancer patients in our population. METHODS: This retrospective study was conducted on all colorectal carcinomas in Hospital Universiti Sains Malaysia (HUSM) in Kelantan from ythe ears 2001-2006. The data were retrieved from the Registry in Pathology laboratory and the clinical details from the patients' clinical records and analyzed using SSPS Version 12.0, with a value of p<0.05 taken to be statistically significant. RESULTS: 138 CRC cases with complete clinical records were included. The age ranged from 16.0 to 88.0 years, with a mean of 56.9 -/+ SD 15.4. The male 90(65%) to female 48(35%) ratio was 1.7:1.0 and 47.8% were suffering from metabolic diseases; 18(13.0%) with Diabetes Mellitus Type 2(DM2), and 48(34.8%) with hypertension (HT). Diabetes Type 2 and hypertension also demonstrated significant association (p<0.05) with the stage and the site of the cancer. Patients with diabetes type 2 88.8%(16/18) and Hypertension 85.4% (41/48) were strongly associated with cancers located in the distal to transverse colon (p<0.001). CONCLUSION: There is a high proportion of metabolic diseases; hypertension and diabetes type 2 among colorectal carcinomas seen in Kelantan population. In this preliminary study we noted a strong association of metabolic diseases with the stage and site of the cancer. To reduce CRC incidence, the high prevalence of DM2 in Kelantan needs to be addressed.