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  1. Elvy Suhana, M.R., Fairus, A., Norazlina, M., Mohamad Fairuz, Y., Ima Nirwana, S.
    Medicine & Health, 2018;13(1):175-197.
    MyJurnal
    Long term glucocorticoids administration induces oxidative stress which leads to alteration of bone structure and strength. Palm oil is rich in tocotrienol, an antioxidant. It can be used for the prevention of oxidative stress related diseases. The main objective of this study was to determine the mechanism of palm tocotrienol in maintaining the bone structure and strength in glucocorticoidinduced osteoporosis. Thirty two adult male Sprague-Dawley rats, aged 3 months, weighing 300-320 g rats were used in this study. Sixteen rats undergone adrenalectomy and were administered with 120µg/kg/day intramuscular injection of dexamethasone. Eight rats were supplemented with oral palm tocotrienol 60 mg/kg/day (Adrx+Dex+PTT) and the other eight rats were given oral vehicle palm olein 0.1 ml/kg/day (Adrx+Dex). Eight rats underwent sham procedure and were given vehicle palm olein 0.05 ml/kg/day by intramuscularly and oral 0.1 ml/kg/day (Sham). The rats were euthanized after two months of treatments. Eight rats were euthanized after acclimatic action without receiving any treatment (Baseline). The right femurs were used for bone biomechanical strength and histomorphometry analysis while the left for gene expression and oxidative stress enzymes activities. The results indicated that long-term glucocorticoid treatment significantly increased bone resorption marker, CTX (6060.7 ± 410 pg/ml) and decreased bone structure and strength. Osteoblast and osteoclast related genes expressions indicated an increase in bone turnover. Supplementation of palm tocotrienol had maintained serum resorption (2619.4 + 209 pg/ml) marker level and preserved bone structure and strength. Gene expression analysis showed decrease in bone resorption. The findings suggested that palm tocotrienol has potential benefits against glucocorticoid-induced osteoporosis by regulating osteoblast and osteoclast related gene expressions.
  2. Nur Ain, J., Ainaa Diyana, S., Nur Hazirah, R., Nur Fathiah, A.S., Fairus, A., Teoh, S.l., et al.
    Medicine & Health, 2018;13(1):165-174.
    MyJurnal
    Piper betle (PB) leaves have been traditionally used in many Asian countries for the healing of wounds and other ailments. The aim of this study was to examine the wound healing effect of PB on skin injury-inflicted Sprague-Dawley rats. Eighteen male Sprague-Dawley rats were inflicted with wounds and then divided into three groups consisting of a control (normal wound healing without dressing), saline (wound healing aided by gauze soaked in saline) and PB (gauze impregnated with PB paste) dressings. Wounds were created on the back of rats with 6-mm sterilized punch biopsy needle. Wounds were examined on days 3, 5, 7, 9, 11 and 13 for dryness, exudation, and scar formation. Rats were sacrificed on day 14 and the granulation tissue formed on the wound was then excised for histological examination using Hematoxylin and Eosin staining. The formation of granulation tissue in rats treated with PB showed higher progress to wound closure with shorter days (on day 3) compared to the control and saline group (on day 5). PB dressing minimized the formation of scar tissue significantly (p
  3. Azwan K, Farihah HS, Fairus A, Elvy MR
    Clin Ter, 2015;166(3):99-104.
    PMID: 26152615 DOI: 10.7417/CT.2015.1837
    A study was done to investigate the effect of palm oil (Elaeis guineensis) tocotrienols on (1) rats mesenteric adipose tissue deposition (2) and 11β-HSD1 enzyme expression in mesenteric adipocyte. There is a necessity to find an inhibitor for the 11β-HSD1 enzyme which enhances the proliferation of mesenteric adipocyte tissue therefore curbing the onset of metabolic syndrome.
  4. Mohamad Fairus AK, Choudhary B, Hosahalli S, Kavitha N, Shatrah O
    Biochimie, 2017 Apr;135:154-163.
    PMID: 28196676 DOI: 10.1016/j.biochi.2017.02.003
    Dihydroorotate dehydrogenase (DHODH) is the key enzyme in de novo biosynthesis of pyrimidine in both prokaryotes and eukaryotes. The de novo pathway of pyrimidine biosynthesis is essential in cancer cells proliferation. Leflunomide is an approved DHODH inhibitor that has been widely used for the treatment of arthritis. Similarly, brequinar sodium is another DHODH inhibitor that showed anti-tumour effect in MC38 colon carcinoma cells when used in combination with fluorouracil. Despite the potential role of DHODH inhibitors in cancer therapy, their mechanisms of action remain obscure and await further elucidation. Here, we evaluated the effect of DHODH inhibitors on the production of ATP and ROS in sensitive and non-sensitive breast cancer cells. Subsequently, the effects of DHODH inhibitors on cell cycle as well as on signalling molecules such as p53, p65 and STAT6 were evaluated in sensitive T-47D and non-sensitive MDAMB-436 cells. The correlations between DHODH protein expression, proliferation speed and sensitivity to DHODH inhibitors were also investigated in a panel of cancer cell lines. DHODH inhibitors-sensitive T-47D and MDAMB-231 cells appeared to preserve ROS production closely to endogenous ROS level whereas the opposite was observed in non-sensitive MDAMB-436 and W3.006 cells. In addition, we observed approximately 90% of intracellular ATP depletion in highly sensitive T-47D and MDAMB-231 cells compared to non-sensitive MDAMB-436 cells. There was significant over-expression of p53, p65 and STAT6 signalling molecules in sensitive cells which may be involved in mediating the S-phase arrest in cell cycle progression. The current study suggests that DHODH inhibitors are most effective in cells that express high levels of DHODH enzyme. The inhibition of cell proliferation by these inhibitors appears to be accompanied by ROS production as well as ATP depletion. The increase in expression of signalling molecules observed may be due to pyrimidine depletion which subsequently leads to cell cycle arrest at S-phase.
  5. Khandaker MU, Zayadi NSB, Sani SFA, Bradley DA, Osman H, Alzamil Y, et al.
    Radiat Prot Dosimetry, 2023 Nov 02;199(18):2174-2178.
    PMID: 37934995 DOI: 10.1093/rpd/ncad179
    Present study concerns the radiological character of Malaysian honey. A total of 18 samples (representative of the various most common types) were obtained from various honey bee farms throughout the country. Using a high-purity germanium γ-ray spectroscopic system, the samples were analysed for the naturally occurring radionuclides 226Ra, 228Ra and 40K. The respective range of activities (in Bq/kg) was: 3.49 ± 0.35 to 4.51 ± 0.39, 0.99 ± 0.37 to 1.74 ± 0.39 and 41.37 ± 3.26 to 105.02 ± 6.91. The estimated associated committed effective doses were derived from prevailing data on national consumption of honey, the annual dose being found low compared with the UNSCEAR reference dose limit of 290 μSv y-1. The estimated threshold consumption rate for honey indicates a maximum intake of 339 g/d, which poses an insignificant radiological risk to public health; however, the total dietary exposure may not, the guidance level of 290 μSv y-1 being applicable to dietary intake of all foodstuffs. The study is in support of the cultivation of a healthy lifestyle, acknowledging prevailing radioactivity within the environment.
  6. Fairus A, Ima Nirwana S, Elvy Suhana MR, Tan MH, Santhana R, Farihah HS
    Clin Ter, 2013;164(1):5-10.
    PMID: 23455734 DOI: 10.7417/CT.2013.1502
    Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone.
  7. Norzana AG, Farihah HS, Fairus A, Teoh SL, Nur AK, Faizah O, et al.
    Clin Ter, 2013;164(1):1-3.
    PMID: 23455733 DOI: 10.7417/CT.2013.1501
    Tibial nerve is a branch of the sciatic nerve and it is the main nerve innervating the muscles of the back of the leg. The tibial nerve divides into medial and lateral plantar nerves. The level of division may be important for surgical purpose. The main aim of the present study was to observe the exact level of division of the tibial nerve and discuss its clinical implications.
  8. Wong SK, Chin KY, Suhaimi FH, Fairus A, Ima-Nirwana S
    Nutr Metab (Lond), 2016;13:65.
    PMID: 27708685 DOI: 10.1186/s12986-016-0123-9
    Metabolic syndrome (MetS) consists of several medical conditions that collectively predict the risk for cardiovascular disease better than the sum of individual conditions. The risk of developing MetS in human depends on synergy of both genetic and environmental factors. Being a multifactorial condition with alarming rate of prevalence nowadays, establishment of appropriate experimental animal models mimicking the disease state in humans is crucial in order to solve the difficulties in evaluating the pathophysiology of MetS in human. This review aims to summarize the underlying mechanisms involved in the pathophysiology of dietary, genetic, and pharmacological models of MetS. Furthermore, we will discuss the usefulness, suitability, pros and cons of these animal models. Even though numerous animal models of MetS have been established, further investigations on the invention of new animal model and clarification of plausible mechanisms are still necessary to confer a better understanding to researchers on the selection of animal models for their studies.
  9. Chin KY, Chan CY, Subramaniam S, Muhammad N, Fairus A, Ng PY, et al.
    Int J Med Sci, 2020;17(16):2585-2593.
    PMID: 33029101 DOI: 10.7150/ijms.49030
    Objectives: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that elevates the individual risk of cardiovascular diseases. These abnormalities are also known to alter bone remodelling. Therefore, MetS may be associated with osteoporosis. This study aims to determine the association between MetS and its components and bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) among Malaysians. Methods: 400 Malaysians aged ≥ 40 years (52.5% women) residing in Klang Valley, Malaysia, were recruited. Subjects' demographic and lifestyle details were collected using a questionnaire, and blood pressure and body anthropometry were measured. Subjects' lumbar spine and total hip BMD were measured by DXA. Their fasting blood was collected for blood glucose level and lipid profile analysis. Regression analysis was used to analyze the relationship between MetS or its components and BMD. Results: Subjects with MetS had higher BMD compared to subjects without MetS in models unadjusted for BMI (spine p=0.008; hip p<0.001). This difference was attenuated with BMI adjustment (spine p=0.625; hip p=0.478). Waist circumference was associated positively with BMD in models unadjusted for BMI (spine p=0.012; hip p<0.001), but the association became negative with BMI adjustment (spine p=0.044; hip p=0.021). Systolic blood pressure was associated positively with total hip BMD (p=0.019) but BMI adjustment attenuated the relationship (p=0.080). Triglyceride level was associated with osteoporosis in a fully adjusted model (p=0.001). Overall, MetS was associated with osteoporosis (p=0.019) but lifestyle (p=0.188) and BMI adjustment attenuated the relationship (p=0.904). Conclusion: MetS is positively associated with BMD, and this relationship is predominantly mediated by BMI. Although MetS is not a significant risk factor for osteoporosis, the inverse relationship between waist circumference, a marker of central obesity, and BMD highlights the need to prevent adiposity to improve metabolic and skeletal health.
  10. Chan CY, Subramaniam S, Mohamed N, Ima-Nirwana S, Muhammad N, Fairus A, et al.
    Arch Osteoporos, 2020 09 12;15(1):142.
    PMID: 32918631 DOI: 10.1007/s11657-020-00821-5
    T-score discordance between hip and spine is a common problem in the diagnosis of osteoporosis based on dual-energy X-ray absorptiometry. Not much information on the prevalence and risk factors of this problem is available in Malaysia. Our study found that factors like age, height, physical activity and menopausal status should be taken into account in the diagnosis of osteoporosis.

    INTRODUCTION AND OBJECTIVE: T-score discordance between hip and spine is a common problem in bone mineral density assessment. A difference ≥ 1 standard deviation (SD) (regardless of diagnostic class) is considered minor, and a difference more than one diagnostic class is considered major discordance. This study aimed to determine the prevalence and factors of hip and spine T-score discordance in a population aged ≥ 40 years in Klang Valley, Malaysia.

    SUBJECTS AND METHODS: In this cross-sectional study, subjects answered a demographic questionnaire and underwent body composition and bone health assessment using dual-energy X-ray absorptiometry. Chi-square and binary logistic regression analysis were used to assess the prevalence of T-score discordance among the subjects.

    RESULTS: A total of 786 Malaysians (382 men, 404 women) subjects were recruited. The prevalence of minor and major discordance was 30.3% and 2.3%, respectively. Overall, factors related to T-score discordance were advanced age, decreased height, and being physically active. Sub-analysis showed that decreased height and being physically active predicted T-score discordance in men, being menopausal and Indian (vs Chinese) were predictors in women.

    CONCLUSIONS: T-score discordance between hip and spine is common among Malaysian middle-aged and elderly population. Diagnosis of osteopenia/osteoporosis should be based on the T-score of more than one skeletal site as per the current recommendations.

  11. Chan CY, Subramaniam S, Chin KY, Ima-Nirwana S, Muhammad N, Fairus A, et al.
    Int J Environ Res Public Health, 2019 Oct 25;16(21).
    PMID: 31731507 DOI: 10.3390/ijerph16214115
    Osteoporosis is a skeletal disorder commonly found among the elderly, in which the bones become weak, brittle, and more susceptible to fracture. Adequate knowledge and positive attitude towards the disease and osteoprotective activities may prevent osteoporosis, but comprehensive studies to verify this hypothesis are limited in Malaysia. This study aims to bridge the research gap by determining the levels of knowledge, beliefs, and practices regarding osteoporosis and their associations with bone mineral density (BMD) among men and women ≥ 40 years in Klang Valley, Malaysia. In this cross-sectional study, 786 Malaysians (382 men, 404 women) completed a questionnaire on knowledge, beliefs, and osteoprotective practices, and underwent BMD scan using a dual-energy X-ray absorptiometry device. The current study found moderate levels of knowledge and beliefs regarding osteoporosis but poor osteoprotective practices. Osteoporosis knowledge, beliefs, and practices were significantly different based on subjects' demographic characteristics (p < 0.05). Osteoporosis knowledge and beliefs were correlated significantly with osteoprotective practices (p < 0.05). Bone health status of the subjects was associated positively with calcium supplement intake, and negatively with exercise barriers and smoking status of the subjects (p < 0.05). However, no significant correlation was noted between osteoporosis knowledge and bone health (p > 0.05). Conclusively, despite some correlations between individual components, the detachment between bone health knowledge and beliefs, and osteoprotective practices among Malaysians is apparent. Integrating all three components into a comprehensive osteoporosis prevention program is warranted.
  12. Chan CY, Subramaniam S, Chin KY, Ima-Nirwana S, Muhammad N, Fairus A, et al.
    Int J Environ Res Public Health, 2022 May 17;19(10).
    PMID: 35627609 DOI: 10.3390/ijerph19106072
    Background: Osteoporosis is an emerging geriatric condition with high morbidity and healthcare cost in developing nations experiencing rapid population ageing. Thus, identifying strategies to prevent osteoporosis is critical in safeguarding skeletal health. This study aimed to evaluate the effects of a bone health screening and education programme on knowledge, beliefs, and practice regarding osteoporosis among Malaysians aged 40 years and above. Methods: A longitudinal study was conducted from April 2018 to August 2019. During the first phase of the study, 400 Malaysians (190 men, 210 women) aged ≥ 40 years were recruited in Klang Valley, Malaysia. Information on subjects’ demography, medical history, knowledge, and beliefs regarding osteoporosis, physical activity status, and dietary and lifestyle practices were obtained. Subjects also underwent body anthropometry measurement and bone mineral density scan (hip and lumbar spine) using a dual-energy X-ray absorptiometry device. Six months after the first screening, similar investigations were carried out on the subjects. Results: During the follow-up session, 72 subjects were lost to follow up. Most of them were younger subjects with a lower awareness of healthy practices. A significant increase in knowledge, beliefs (p < 0.05), calcium supplement intake (p < 0.001), and dietary calcium intake (p = 0.036) and a reduction in coffee intake (p < 0.001) were found among subjects who attended the follow-up. In this study, the percentage of successful referrals was 41.86%. Subjects with osteoporosis were mostly prescribed alendronate plus vitamin D3 by medical doctors, and they followed the prescribed treatment accordingly. Conclusions: The bone health screening and education programmes in this study are effective in changing knowledge, beliefs, and practice regarding osteoporosis. The information is pertinent to policymakers in planning strategies to prevent osteoporosis and its associated problems among the middle-aged and elderly population in Malaysia. Nevertheless, a more comprehensive bone health education program that includes long-term monitoring and consultation is needed to halt the progression of bone loss.
  13. Low NY, Chan CY, Subramaniam S, Chin KY, Ima Nirwana S, Muhammad N, et al.
    Ann Hum Biol, 2022 Dec;49(7-8):299-304.
    PMID: 36373795 DOI: 10.1080/03014460.2022.2147585
    BACKGROUND: Body mass index (BMI) is a widely used surrogate tool to screen for obesity/adiposity, but it cannot differentiate between lean and fat mass. Thus, alternative tools to detect excess adiposity should be identified.

    AIM: This study aimed to compare the performance of BMI, waist circumference (WC) and waist-to-height ratio (WtHR) in predicting Malaysians with excess body fat defined by dual-energy X-ray absorptiometry (DXA).

    SUBJECTS AND METHODS: A total of 399 men and women aged ≥40 years were recruited from Klang Valley, Malaysia. The body composition of the subjects, including body fat percentage, was measured by DXA. The weight, height, WC and WHtR of the subjects were also determined.

    RESULTS: BMI [sensitivity = 55.7%, specificity = 86.1%, area under curve (AUC) = 0.709] and WC (sensitivity = 62.7%, specificity = 90.3%, AUC = 0.765) performed moderately in predicting excess adiposity. Their performance and sensitivity improved with lower cut-off values. The performance of WHtR (sensitivity = 96.6%, specificity = 36.1, AUC = 0.664) was optimal at the standard cut-off value and no modification was required.

    CONCLUSION: The performance of WC in identifying excess adiposity was greater than BMI and WHtR based on AUC values. Modification of cut-off values for BMI and WC could improve their performance and should be considered by healthcare providers in screening individuals with excess adiposity.

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