Displaying publications 21 - 40 of 49 in total

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  1. Omar NO, Ahmad RA, Mohd Shah MS, Aminuddin AA, Chellappan KC
    Med J Malaysia, 2021 05;76(3):375-381.
    PMID: 34031337
    INTRODUCTION: Inflammation plays a central role in the pathogenesis of cardiovascular events. The lack of exercise among Malaysians and the increasing cardiovascular diseases among young men are of concern. The aim of this study was to evaluate the reducing of inflammation by measuring C-Reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α).

    MATERIALS AND METHODS: A total of 70 young men (20 - 40 years) who were sedentary, achieving less than 5,000 steps/day in casual walking with 2 or more cardiovascular risk factors were recruited in Institute of Vocational Skills for Youth (IKBN Hulu Langat). Subjects were randomly assigned to a control group (CG) (n=34; no change in walking) and pedometer group (PG) (n=36; minimum target: 8,000 steps/day). All parameter was measured at baseline, at 6 weeks and after 12 weeks.

    RESULTS: At post intervention, the CG step counts were similar (4983 ± 366vs 5697 ± 407steps/day). The PG significant increased step count from 4996 ± 805 to 10,128 ±511 steps/day (p<0.001). The PG showed significant improvement in anthropometric variables and lipid (time and group effect p<0.001). After intervention, CRP, IL-6 and TNF- α were significantly reduced for time and group effect (p<0.001). However, no changes were seen in CG.

    CONCLUSION: The pedometer-based walking programme improved health status in terms of improving inflammation and arterial stiffness.

  2. Ab Hamid F, Che Azemin MZ, Salam A, Aminuddin A, Mohd Daud N, Zahari I
    Curr Eye Res, 2016 Jun;41(6):823-31.
    PMID: 26268475 DOI: 10.3109/02713683.2015.1056375
    PURPOSE: The goal of this study was to provide the empirical evidence of fractal dimension as an indirect measure of retinal vasculature density.

    MATERIALS AND METHODS: Two hundred retinal samples of right eye [57.0% females (n = 114) and 43.0% males (n = 86)] were selected from baseline visit. A custom-written software was used for vessel segmentation. Vessel segmentation is the process of transforming two-dimensional color images into binary images (i.e. black and white pixels). The circular area of approximately 2.6 optic disc radii surrounding the center of optic disc was cropped. The non-vessels fragments were removed. FracLac was used to measure the fractal dimension and vessel density of retinal vessels.

    RESULTS: This study suggested that 14.1% of the region of interest (i.e. approximately 2.6 optic disk radii) comprised retinal vessel structure. Using correlation analysis, vessel density measurement and fractal dimension estimation are linearly and strongly correlated (R = 0.942, R(2) = 0.89, p 

  3. Omar N, Yeoh BS, Chellappan K, Chui SZ, Salamt N, Aminuddin A
    Front Physiol, 2023;14:1062751.
    PMID: 37057183 DOI: 10.3389/fphys.2023.1062751
    Introduction: Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality in Malaysia and worldwide. This is mainly due to an increase in the prevalence of CVD risk factors such as hypertension, dyslipidemia, smoking, and obesity. Increased physical activity has been recommended as a modality to improve CVD risk. Pulse wave velocity (PWVCF), augmentation index (AI), and finger photoplethysmography fitness (PPGF) index have been introduced to assess the vascular functions related to CVD risk factors. The effects of long-term exercise on PPGF index are not established. Materials and Methods: A total of 70 young men who were sedentary with two or more cardiovascular risk factors were recruited. Subjects were randomly assigned to a control group (CG) (n = 34; no change in walking) and pedometer group (PG) (n = 36; minimum target: 8,000 steps/day). PWVCF and AI were measured via the Vicorder system. The PPGF index was obtained via the finger photoplethysmography method. All parameters were measured at baseline and after 6 and 12 weeks. Results: After intervention, the PG had significant increased step count from 4,996 ± 805 to 10,128 ± 511 steps/day (p < 0.001). The PG showed significant improvement in anthropometric variables, lipid, PWVCF, AI, and PPGF index (time and group effect p < 0.001). No changes were observed in CG. Conclusion: This signifies that pedometer-based walking program is beneficial in improving markers of vascular functions among young working sedentary men with CVD risk factors. Pedometer-based exercise should be encouraged to improve cardiovascular health.
  4. Rami AZA, Hamid AA, Anuar NNM, Aminuddin A, Ugusman A
    Mediators Inflamm, 2022;2022:2734321.
    PMID: 35177953 DOI: 10.1155/2022/2734321
    Initially thought to only provide mechanical support for the underlying blood vessels, perivascular adipose tissue (PVAT) has now emerged as a regulator of vascular function. A healthy PVAT exerts anticontractile and anti-inflammatory actions on the underlying vasculature via the release of adipocytokines such as adiponectin, nitric oxide, and omentin. However, dysfunctional PVAT produces more proinflammatory adipocytokines such as leptin, resistin, interleukin- (IL-) 6, IL-1β, and tumor necrosis factor-alpha, thus inducing an inflammatory response that contributes to the pathogenesis of vascular diseases. In this review, current knowledge on the role of PVAT inflammation in the development of vascular pathologies such as atherosclerosis and hypertension was discussed.
  5. Lau CC, Aminuddin A, Chan KM, Paterson IC, Law LM, Ng PY
    Life (Basel), 2021 Nov 02;11(11).
    PMID: 34833046 DOI: 10.3390/life11111170
    Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell lines and the potential mechanisms involved. Through GEPIA dataset analysis, high expression levels of mRNA encoding P2Y receptors, the ATP-induced G protein-coupled receptors, were associated with better overall patient survival in head and neck squamous cell carcinoma. qPCR analysis showed that the poorly differentiated OSCC SAS cell line, had higher P2RY1 expression level compared to the well-differentiated H103 and H376 cell lines. Western blotting and flow cytometry analyses revealed that ATP phosphorylated ERK and elevated intracellular calcium signaling in all tested cell lines. A significant S-phase cell cycle arrest was observed in SAS, and preincubation with the MEK inhibitor PD0325901 reversed the ATP-induced S-phase arrest. We further demonstrated that ATP induced a slight reduction in cell count and colony formation yet significant apoptosis in SAS. Overall, we postulate that the ATP-induced S-phase arrest effect in SAS cells may be regulated through P2Y receptor-mediated ERK signaling, thus suggesting a potential antitumor effect of ATP via interaction with its distinct profile of P2Y receptors.
  6. Abd Rami AZ, Aminuddin A, Hamid AA, Mokhtar MH, Ugusman A
    Int J Mol Sci, 2023 Oct 12;24(20).
    PMID: 37894791 DOI: 10.3390/ijms242015100
    Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ-adiponectin-adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ-adiponectin-adipoR1 axis.
  7. Aminuddin A, Salamt N, Ahmad Fuad AF, Chin KY, Ugusman A, Soelaiman IN, et al.
    Medicina (Kaunas), 2019 Sep 08;55(9).
    PMID: 31500378 DOI: 10.3390/medicina55090575
    Background and objectives: Obesity is associated with poor vascular function and may lead to future cardiovascular disease (CVD). Obesity is also related to increased inflammation and a low testosterone level. This study was conducted to determine the relationship between inflammation, testosterone level, and vascular function among subjects with an increased body mass index (BMI) and to determine whether both low testosterone and high inflammation have synergistic effects towards vascular dysfunction. Materials and Methods: A total of 303 men aged 40-80 years were recruited from Klang Valley, Malaysia. Their height, weight, blood pressure (BP), lipid, blood glucose level, total testosterone (TT), free testosterone (FT), and C-reactive protein (CRP) were measured. The carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) were also recorded as markers of vascular function. Results: The mean age of all the subjects was 54.46 ± 9.77 years. Subjects were divided into a low/normal body mass index (BMI) group (BMI < 25 kg/m2; NG, n = 154) and high BMI group (BMI ≥ 25 kg/m2; OG, n = 149). The mean BMI for NG was 22.20 ± 1.94 kg/m2 while for OG was 28.87 ± 3.24 kg/m2 (p < 0.01). The level of TT (OG = 21.13 ± 6.44 versus NG = 16.18 ± 6.16 nmol/L, p < 0.01) and FT (OG = 0.34 ± 0.12 versus NG = 0.39 ± 0.11 nmol/L, p < 0.01) were reduced while the level of CRP [OG = 1.05 (2.80) versus NG = 0.50 (1.50) mmol/L, p = 0.01] was increased in OG compared to NG. PWVCF (OG = 8.55 ± 1.34 versus NG = 8.52 ± 1.42 m/s, p = 0.02) and AI (OG = 16.91% ± 6.00% versus 15.88% ± 5.58%, p < 0.01) were significantly increased in OG after adjustment for other CVD risk factors. The subjects that had both a low FT and an increased CRP had higher AI when compared to those with a high CRP and high FT (p < 0.01). Conclusions: The increased BMI was associated with vascular dysfunction, mediated by a low testosterone level and increased inflammation. Furthermore, having both conditions concurrently lead to higher vascular dysfunction. Weight loss, testosterone supplementation, and the anti-inflammatory agent may be beneficial for men to prevent vascular dysfunction.
  8. Chin KY, Soelaiman IN, Mohamed IN, Ahmad F, Ramli ES, Aminuddin A, et al.
    Clinics (Sao Paulo), 2013;68(2):159-66.
    PMID: 23525310
    OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia.

    METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses.

    RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40.

    CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

  9. Othman NS, Che Roos NA, Aminuddin A, Murthy JK, A Hamid A, Ugusman A
    Front Pharmacol, 2022;13:976247.
    PMID: 36091787 DOI: 10.3389/fphar.2022.976247
    Hypertension and diabetes mellitus are among the most prevalent diseases affecting people from all walks of life. Medicinal herbs have garnered interest as potential agents for the prevention and treatment of diabetes mellitus and hypertension due to their multiple beneficial effects. Piper sarmentosum Roxb. (PS) is an edible medicinal plant that has been traditionally used in Asia for treating hypertension and diabetes mellitus. This review is aimed to provide comprehensive information from the literature on the effects of PS on hypertension and diabetes mellitus. A computerized database search was performed on Scopus, PubMed and Web of Science databases with the following set of keywords: Piper sarmentosum AND diabetes mellitus OR diabetic OR diabetes OR hyperglyc*emia OR blood glucose OR HbA1c OR glycated h*emoglobin OR h*emoglobin A1c OR hyperten* OR blood pressure. A total of 47 articles were screened and 14 articles published between the years 1998 until 2021 were included for data extraction, comprising of six articles on antihypertensive and eight articles on antidiabetic effects of PS. These studies consist of two in vitro studies and eleven in vivo animal studies. Meta-analysis of three studies on hypertension showed that PS versus no treatment significantly lowered the systolic blood pressure with mean difference (MD) -39.84 mmHg (95% confidence interval (CI) -45.05, -34.62; p < 0.01), diastolic blood pressure with MD -26.68 mmHg (95% CI -31.48, -21.88; p < 0.01), and mean arterial pressure with MD -30.56 mmHg (95% CI -34.49, -26.63; p < 0.01). Most of the studies revealed positive effects of PS against hypertension and diabetes mellitus, suggesting the potential of PS as a natural source of antidiabetic and antihypertensive agents.
  10. Abd Rahman IZ, Nor Hisam NS, Aminuddin A, Hamid AA, Kumar J, Ugusman A
    Pharmaceuticals (Basel), 2023 Nov 09;16(11).
    PMID: 38004453 DOI: 10.3390/ph16111588
    Plukenetia volubilis Linneo or Sacha Inchi (SI), a traditional natural remedy indigenous to Peru and Brazil, has garnered global attention due to its exceptional nutritional composition. Its protective effects against various non-communicable diseases, notably cardiovascular disease (CVD), have become a subject of interest in recent research. This comprehensive review summarizes the existing evidence from 15 relevant articles concerning the impact of SI on common CVD risk factors, including dyslipidemia, obesity, diabetes, and hypertension. The relevant articles were derived from comprehensive searches on PubMed, Scopus, Google Scholar, and Web of Science using predefined criteria and keywords related to the topic. Overall, SI demonstrated positive effects in attenuating dyslipidemia, obesity, diabetes, and hypertension. The multifaceted mechanisms responsible for the protective effects of SI against these CVD risk factors are primarily attributed to its antioxidative and anti-inflammatory properties. While preclinical studies dominate the current scientific literature on SI, there are limited clinical trials to corroborate these findings. Therefore, future well-designed, large-scale randomized clinical trials are highly recommended to establish the efficacy of SI and determine its optimal dosage, potential drug and food interactions, and practical integration into preventive strategies and dietary interventions for the high-risk populations.
  11. Abdullah B, Idris S, Md Jaafar SA, Ghazali NLA, Mat Liki NS, Aminuddin AA
    Med J Malaysia, 2023 Nov;78(6):768-773.
    PMID: 38031219
    INTRODUCTION: The aim of this study is to determine the level of awareness of pelvic organ prolapse (POP) and factors that influence the attitude towards the treatment of POP among Malaysian women.

    MATERIALS AND METHODS: This was a cross-sectional study of 400 women from registered non-government organisations (NGOs) in Malaysia who voluntarily answered questionnaires distributed through Google form via emails. Data were analysed using descriptive statistics, independent t-test and one-way ANOVA test.

    RESULTS: Four hundred respondents participated in this study. The mean age was 40.42 years old (SD=12.566). The mean score for the studied population was 4.96 (SEM 0.124). Only 58 (14.5%) respondents obtained a score of eight or more, and 235 (58.8%) respondents scored between 4 and 7. The rest of 107 (26.7%) respondents scored 3 and less. There were statistically significant differences in the mean score for level of awareness between marital statuses, menopausal status, number of children and occupation. There were only 273 (68%) respondents who will seek treatment if they experience symptoms of POP. The most frequent reasons for not seeking treatment were unawareness of the availability of medical treatment for POP (69 %).

    CONCLUSION: Majority of the respondents have an inadequate level of awareness on POP. Although more than half of the respondents will seek treatment if they experience symptoms of POP, concerns raised by those who chose not to seek treatment should be addressed by a more effective public awareness programme. This includes the unawareness of the availability of medical treatment and the embarrassment to see medical practitioners.

  12. Saud Gany SL, Chin KY, Tan JK, Aminuddin A, Makpol S
    Front Pharmacol, 2023;14:1290721.
    PMID: 38146461 DOI: 10.3389/fphar.2023.1290721
    Musculoskeletal health is paramount in an ageing population susceptible to conditions such as osteoporosis, arthritis and fractures. Age-related changes in bone, muscle, and joint function result in declining musculoskeletal health, reduced mobility, increased risk of falls, and persistent discomfort. Preserving musculoskeletal wellbeing is essential for maintaining independence and enhancing the overall quality of life for the elderly. The global burden of musculoskeletal disorders is significant, impacting 1.71 billion individuals worldwide, with age-related muscle atrophy being a well-established phenomenon. Tocotrienols, a unique type of vitamin E found in various sources, demonstrate exceptional antioxidant capabilities compared to tocopherols. This characteristic positions them as promising candidates for addressing musculoskeletal challenges, particularly in mitigating inflammation and oxidative stress underlying musculoskeletal disorders. This review paper comprehensively examines existing research into the preventive and therapeutic potential of tocotrienols in addressing age-related musculoskeletal issues. It sheds light on the promising role of tocotrienols in enhancing musculoskeletal health and overall wellbeing, emphasizing their significance within the broader context of age-related health concerns.
  13. Supa'at I, Zakaria Z, Maskon O, Aminuddin A, Nordin NA
    PMID: 24023571 DOI: 10.1155/2013/171852
    Swedish Massage Therapy (SMT) is known for its therapeutic relaxation effects. Hypertension is associated with stress and elevated endothelial inflammatory markers. This randomized control trial measured the effects of whole body SMT (massage group) or resting (control group) an hour weekly for four weeks on hypertensive women. Blood pressure (BP) and heart rate (HR) were measured before and after each intervention and endothelial inflammatory markers: vascular endothelial adhesion molecules 1 (VCAM-1) and intracellular adhesion molecules 1 (ICAM-1) were measured at baseline and after the last intervention. Massage group (n=8) showed significant systolic BP (SBP) reduction of 12 mmHg (P=0.01) and diastolic BP (DBP) reduction of 5 mmHg (P=0.01) after four sessions with no significant difference between groups. Reductions in HR were also seen in massage group after sessions 1, 3, and 4 with significant difference between groups. VCAM-1 showed significant reduction after four sessions: the massage group showed reduction of 998.05 ng/mL (P=0.03) and the control group of 375.70 ng/mL (P=0.01) with no significant differences between groups. There were no changes in ICAM-1. In conclusion, SMT or resting an hour weekly has effects on reducing BP, HR, and VCAM-1 in hypertensive women.
  14. Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Ngah WZ
    Exp. Clin. Endocrinol. Diabetes, 2013 Jul;121(7):407-12.
    PMID: 23765753 DOI: 10.1055/s-0033-1345164
    Testosterone and sex hormone-binding globulin (SHBG) have been shown to be associated with metabolic syndrome (MS) in men. This study aimed at validating these relationships in a group of middle-aged and elderly men and assessing their strength of association to MS. A cross-sectional study of 332 Malaysian men aged 40 years and above was conducted. The blood of subject was collected under fasting condition for determination of testosterone, SHBG, glucose and lipid levels. Their medical history, smoking and alcohol consumption status, waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. All testosterone and SHBG levels were significantly reduced in MS subjects compared to non-MS subjects (p<0.05). Testosterone and SHBG were correlated significantly with most of the MS indicators without adjustments. In multiple regression analysis, the triglyceride level was the only MS indicator that was significantly, inversely and independently associated with all testosterone measurements and SHBG (p<0.05). Waist circumference was significantly and negatively associated with SHBG level (p<0.05) though not independent of BMI. Total testosterone and SHBG were significantly and inversely associated with the presence of MS. Testosterone and SHBG are potential intervention targets for the prevention of MS in men.
  15. Ismail SM, Sundar UM, Hui CK, Aminuddin A, Ugusman A
    J Taibah Univ Med Sci, 2018 Jun;13(3):225-231.
    PMID: 31435328 DOI: 10.1016/j.jtumed.2018.01.003
    Objectives: Inflammation plays a key role in the pathogenesis of atherosclerosis. Piper sarmentosum is an herb with antioxidant and anti-atherosclerotic activities. The aim of this study was to evaluate the anti-inflammatory properties of an aqueous extract of P. sarmentosum (AEPS) in human umbilical vein endothelial cells (HUVECs).

    Methods: HUVECs were divided into six groups: control, treatment with 10 ng/ml TNF-α, and co-treatment of 10 ng/ml TNF-α with four different concentrations of AEPS (100, 150, 250, and 300 μg/ml) for 24 h. Subsequently, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression, U937 monocyte cells adhesion, and nuclear factor-kappaB (NF-κB) p65 expression in HUVECs were measured.

    Results: Treatment of TNF-α-stimulated HUVECs with AEPS at different concentrations resulted in decreased VCAM-1 and ICAM-1 protein expression in a dose-dependent manner. Furthermore, AEPS also inhibited TNF-α-stimulated U937 monocyte cells adhesion to HUVECs. In addition, AEPS reduced TNF-α-induced NF-κB p65 expression in a dose-dependent manner.

    Conclusions: The results indicated that AEPS suppressed TNF-α-induced VCAM-1 and ICAM-1 expression NF-κB signaling.

  16. Sundar UM, Ugusman A, Chua HK, Latip J, Aminuddin A
    Front Pharmacol, 2019;10:1033.
    PMID: 31607906 DOI: 10.3389/fphar.2019.01033
    Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS). ADMA is degraded by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of ADMA lead to reduction in nitric oxide (NO) production, which is linked to endothelial dysfunction and atherosclerosis. Piper sarmentosum is an herb that has shown stimulation on endothelial NO production by increasing both expression and activity of eNOS. Thus, this study determined whether the positive effect of P. sarmentosum on NO production is related to its modulation on the DDAH-ADMA pathway in cultured human umbilical vein endothelial cells (HUVEC) exposed to tumor necrosis factor-α (TNF-α). HUVEC were divided into four groups: control, treatment with 250 µg/ml of aqueous extract of P. sarmentosum leaves (AEPS), treatment with 30 ng/ml of TNF-α, and concomitant treatment with AEPS and TNF-α for 24 h. After treatments, HUVEC were collected to measure DDAH1 messenger RNA (mRNA) expression using quantitative real-time polymerase chain reaction. DDAH1 protein level was measured using enzyme-linked immunosorbent assay (ELISA), and DDAH enzyme activity was measured using colorimetric assay. ADMA concentration was measured using ELISA, and NO level was measured using Griess assay. Compared to control, TNF-α-treated HUVEC showed reduction in DDAH1 mRNA expression (P < 0.05), DDAH1 protein level (P < 0.01), and DDAH activity (P < 0.05). Treatment with AEPS successfully increased DDAH1 mRNA expression (P < 0.05), DDAH1 protein level (P < 0.01), and DDAH activity (P < 0.05) in TNF-α-treated HUVEC. Treatment with TNF-α caused an increase in ADMA level (P < 0.01) and a decrease in endothelial NO production (P < 0.001). Whereas treatment with AEPS was able to reduce ADMA level (P < 0.01) and restore NO (P < 0.001) in TNF-α-treated HUVEC. The results suggested that AEPS promotes endothelial NO production by stimulating DDAH activity and thus reducing ADMA level in TNF-α-treated HUVEC.
  17. Aminuddin A, Ng PY, Leong CO, Chua EW
    Sci Rep, 2020 May 12;10(1):7885.
    PMID: 32398775 DOI: 10.1038/s41598-020-64664-3
    Cisplatin is the first-line chemotherapeutic agent for the treatment of oral squamous cell carcinoma (OSCC). However, the intrinsic or acquired resistance against cisplatin remains a major obstacle to treatment efficacy in OSCC. Recently, mitochondrial DNA (mtDNA) alterations have been reported in a variety of cancers. However, the role of mtDNA alterations in OSCC has not been comprehensively studied. In this study, we evaluated the correlation between mtDNA alterations (mtDNA content, point mutations, large-scale deletions, and methylation status) and cisplatin sensitivity using two OSCC cell lines, namely SAS and H103, and stem cell-like tumour spheres derived from SAS. By microarray analysis, we found that the tumour spheres profited from aberrant lipid and glucose metabolism and became resistant to cisplatin. By qPCR analysis, we found that the cells with less mtDNA were less responsive to cisplatin (H103 and the tumour spheres). Based on the findings, we theorised that the metabolic changes in the tumour spheres probably resulted in mtDNA depletion, as the cells suppressed mitochondrial respiration and switched to an alternative mode of energy production, i.e. glycolysis. Then, to ascertain the origin of the variation in mtDNA content, we used MinION, a nanopore sequencer, to sequence the mitochondrial genomes of H103, SAS, and the tumour spheres. We found that the lower cisplatin sensitivity of H103 could have been caused by a constellation of genetic and epigenetic changes in its mitochondrial genome. Future work may look into how changes in mtDNA translate into an impact on cell function and therefore cisplatin response.
  18. Aminuddin A, Cheong SS, Roos NAC, Ugusman A
    Int J Med Sci, 2023;20(4):482-492.
    PMID: 37057211 DOI: 10.7150/ijms.79889
    Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; I2 =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.
  19. Samah N, Ugusman A, Hamid AA, Sulaiman N, Aminuddin A
    Mediators Inflamm, 2023;2023:9715114.
    PMID: 37457745 DOI: 10.1155/2023/9715114
    Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the Newcastle-Ottawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy.
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