APPROACH AND RESULTS: Human atherosclerotic plaques showed marked mitochondrial dysfunction, manifested as reduced mtDNA copy number and oxygen consumption rate in fibrous cap and core regions. Vascular smooth muscle cells derived from plaques showed impaired mitochondrial respiration, reduced complex I expression, and increased mitophagy, which was induced by oxidized low-density lipoprotein. Apolipoprotein E-deficient (ApoE-/-) mice showed decreased mtDNA integrity and mitochondrial respiration, associated with increased mitochondrial reactive oxygen species. To determine whether alleviating mtDNA damage and increasing mitochondrial respiration affects atherogenesis, we studied ApoE-/- mice overexpressing the mitochondrial helicase Twinkle (Tw+/ApoE-/-). Tw+/ApoE-/- mice showed increased mtDNA integrity, copy number, respiratory complex abundance, and respiration. Tw+/ApoE-/- mice had decreased necrotic core and increased fibrous cap areas, and Tw+/ApoE-/- bone marrow transplantation also reduced core areas. Twinkle increased vascular smooth muscle cell mtDNA integrity and respiration. Twinkle also promoted vascular smooth muscle cell proliferation and protected both vascular smooth muscle cells and macrophages from oxidative stress-induced apoptosis.
CONCLUSIONS: Endogenous mtDNA damage in mouse and human atherosclerosis is associated with significantly reduced mitochondrial respiration. Reducing mtDNA damage and increasing mitochondrial respiration decrease necrotic core and increase fibrous cap areas independently of changes in reactive oxygen species and may be a promising therapeutic strategy in atherosclerosis.
METHODS: A retrospective analysis of all attempted laparoscopic appendicectomies over 12 months by experienced surgeons and registrars was done. Factors evaluated were operating time, conversion rate, postoperative hospital stay, morbidity and mortality.
RESULTS: There was no statistically significant difference in operating time for surgeons and registrars (mean, 53 minutes vs. 60 minutes), conversion rate (10% vs. 11%). Mean hospital stay for patients operated on by surgeons was 3.1 days and 3.2 days for registrars. Morbidity was equal with both surgeons and registrars.
CONCLUSION: We conclude that laparoscopic appendicectomy is a safe laparoscopic training tool for registrars with basic laparoscopic knowledge who have had a proper apprenticeship, and can be done in a clinical setting.
METHODS: A retrospective descriptive study was conducted on secondary data of all newly diagnosed breast cancer women from 1st August 2011 to 28th February 2014. Secondary data includes age, ethnicity, marital status, family history, education level, occupation, presenting symptom, duration of symptom, tumour size, tumour pathology, tumour grading, oestrogen, progesterone and HER-2 receptor status were collected and analysed using SPSS version 20.0.0.
RESULT: In total, data from 52 women was analysed and two women were excluded for incompleteness as these women defaulted. Late stage at presentation was 59.6% of all new cases (17.3% stage III and 42.3% stage IV). The commonest age group of all women diagnosed with breast cancer was in the 5th decade. Majority of them were Malay, married and housewives with no family history of breast cancer. The statistically significant factors associated with late stage at presentation include Malay ethnicity (p=0.019), presenting symptoms other than breast lump (p=0.047), and duration of breast lump more than 3 months (p=0.009).
DISCUSSION/CONCLUSION: The study demonstrated presentation at late stage of breast cancer is a major health concern among Malaysian women in district hospital. This may be attributed to different sociocultural beliefs, strong belief in complementary and alternative medicine, lack of awareness, and difficult accessibility to healthcare services.
OBJECTIVE: This study aimed to elucidate the impact of the ELEAI on proinflammatory marker gene expression induced by isoniazid (INH).
METHODS: A total of 36 rats were systematically divided into six experimental groups. The control group received DMSO orally for the initial 30 days followed by distilled water for the subsequent 30 days. The INH group received a daily dose of INH (30 mg/kg b.w., i.p.) for 30 days and the rats were then sacrificed on day 30. The ELEAI (250 mg/kg) group was administered INH daily for 30 days, followed by daily post-treatment with ELEAI (250 mg/kg) for another 30 days. Similarly, the ELEAI (500 mg/kg) group received INH daily for 30 days, followed by daily post-treatment with ELEAI (500 mg/kg) for another 30 days. The silymarin (SIL) group was given INH daily for 30 days, followed by post-treatment with SIL at a dose of 100 mg/kg body weight daily for the subsequent 30 days. Finally, the ELEAI (500 mg/kg) alone group was administered distilled water orally for the first 30 days and then received ELEAI at a dose of 500 mg/kg b.w. orally once daily for the next 30 days.
RESULTS: Continuous INH exposure for a month led to a pronounced increase in proinflammatory genes like TNF-α, TGF-β, and NF-kB and a decrease in the IkB gene in rat liver tissues. Subsequent treatment with SIL (100 mg/kg) and ELEAI (250 and 500 mg/kg) post-INH exposure resulted in a marked decrease in proinflammatory genes and a surge in IkB expression.
CONCLUSION: The findings suggest that the ELEAI exerts a dose-responsive influence on proinflammatory activities. Notably, A. indicum counteracts inflammation, especially that triggered by bradykinin and prostaglandins. The ELEAI showcases promising therapeutic potential, exhibiting both pro and anti-inflammatory properties and antiproliferative characteristics.