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Fulltext The role of vitamin E in preventing and treating osteoarthritis - a review of the current evidence

Chin KY, Ima-Nirwana S

Front Pharmacol, 2018;9:946.
PMID: 30186176 DOI: 10.3389/fphar.2018.00946

Osteoarthritis is a debilitating disease of the joint involving cartilage degeneration and chondrocytes apoptosis. Oxidative stress is one of the many proposed mechanisms underpinning joint degeneration in osteoarthritis. The current pharmacotherapies emphasize pain and symptomatic management of the patients but do not alter the biological processes underlying the cartilage degeneration. Vitamin E is a potential agent to prevent or treat osteoarthritis due to its antioxidant and anti-inflammatory effects. This review aims to summarize the current evidence on the relationship between vitamin E and osteoarthritis derived from preclinical and human studies. Cellular studies showed that vitamin E mitigated oxidative stress in cartilage explants or chondrocyte culture invoked by mechanical stress or free radicals. Animal studies suggested that vitamin E treatment prevented cartilage degeneration and improve oxidative status in animal models of osteoarthritis. Low circulating or synovial vitamin E was observed in human osteoarthritic patients compared to healthy controls. Observational studies also demonstrated that vitamin E was related to induction or progression of osteoarthritis in the general population. Vitamin E supplementation might improve the outcomes in patients with osteoarthritis, but negative results were also reported. Different isomers of vitamin E might possess distinct anti-osteoarthritic effects. As a conclusion, vitamin E may retard the progression of osteoarthritis by ameliorating oxidative stress and inflammation of the joint. Further studies are warranted to develop vitamin E as an anti-osteoarthritis agent to reduce the global burden of this disease.
A Review on the Effects of Testosterone Supplementation in Hypogonadal Men with Cognitive Impairment

Mohamad NV, Ima-Nirwana S, Chin KY

Curr Drug Targets, 2018;19(8):898-906.
PMID: 28914204 DOI: 10.2174/1389450118666170913162739

Cognitive function and testosterone level of men decline concurrently with age. Low testosterone levels are associated with higher risk of Alzheimer's disease and mild cognitive impairment in men. There are continuous debates on whether this relationship is casual. This paper aims to summarize the current evidence on the association between testosterone level and cognitive function in elderly men. The presence of testosterone, androgen receptor and its responsive genes indicates that testosterone has biological functions in the central nervous system. The ability of the body to convert testosterone into estrogen suggests that part of the actions of testosterone could be mediated by estrogen. Observational studies generally showed that low endogenous testosterone levels were associated with poor cognitive performance in healthy elderly men. Testosterone substitution exerted positive effects on certain cognitive domains in normal and hypogonadal elderly men. In conclusion, testosterone may influence cognitive function in elderly men and its substitution may be considered in men with cognitive impairment and testosterone deficiency.
Vitamin D and Depression: The Evidence from an Indirect Clue to Treatment Strategy

Wong SK, Chin KY, Ima-Nirwana S

Curr Drug Targets, 2018;19(8):888-897.
PMID: 28914205 DOI: 10.2174/1389450118666170913161030

Depression is a common psychiatric disorder that decreases the quality of life and increases the mortality of patients. It incurs significant healthcare costs if left untreated. Even though intervention with antidepressants can reduce depressive symptoms, side effects are often an issue and relapse is very common. Vitamin D, commonly known as the sunshine vitamin, is an essential fat-soluble vitamin for the absorption of calcium to prevent rickets (children) and osteomalacia (adults). Evidence on a possible relationship between vitamin D deficiency and depression is growing. In this review, the authors summarized the evidence on the association between vitamin D status and depression in human observational studies, followed by clinical trials to evaluate the effects of vitamin D supplementation in treating depression. In conclusion, vitamin D deficiency may be associated with an increased risk or severity of depression. Supplementation of vitamin D may confer protection for depressed patients.
Fulltext Effects of metabolic syndrome on bone mineral density, histomorphometry and remodelling markers in male rats

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

PLoS One, 2018;13(2):e0192416.
PMID: 29420594 DOI: 10.1371/journal.pone.0192416

This study aimed to evaluate the effects of metabolic syndrome (MetS) induced by high-carbohydrate high-fat (HCHF) diet on bone mineral density (BMD), histomorphometry and remodelling markers in male rats. Twelve male Wistar rats aged 12 weeks old were randomized into two groups. The normal group was given standard rat chow while the HCHF group was given HCHF diet to induce MetS. Abdominal circumference, blood glucose, blood pressure, and lipid profile were measured for the confirmation of MetS. Bone mineral density, histomorphometry and remodelling markers were evaluated for the confirmation of bone loss. The HCHF diet caused central obesity, hyperglycaemia, hypertension, and dyslipidaemia in male rats. No significant difference was observed in whole body bone mineral content and BMD between the normal and HCHF rats (p>0.05). For bone histomorphometric parameters, HCHF diet-fed animals had significantly lower osteoblast surface, osteoid surface, osteoid volume, and significantly higher eroded surface; resulting in a reduction in trabecular bone volume (p<0.05). Feeding on HCHF diet caused a significantly higher CTX-1 level (p<0.05), but did not cause any significant change in osteocalcin level compared to normal rats (p>0.05). In conclusion, HCHF diet-induced MetS causes imbalance in bone remodelling, leading to the deterioration of trabecular bone structure.
Fulltext Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: a temporal sequential study

Wan Hasan WN, Abd Ghafar N, Chin KY, Ima-Nirwana S

Drug Des Devel Ther, 2018;12:1715-1726.
PMID: 29942115 DOI: 10.2147/DDDT.S168935

PURPOSE: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis. However, detailed studies of the effects of AnTT on preosteoblastic cells were limited. This study was conducted to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a time-dependent manner.
MATERIALS AND METHODS: Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.
RESULTS: The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).
CONCLUSION: Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.
Fulltext The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence

Wong SK, Mohamad NV, Ibrahim N', Chin KY, Shuid AN, Ima-Nirwana S

Int J Mol Sci, 2019 Mar 22;20(6).
PMID: 30909398 DOI: 10.3390/ijms20061453

Bone remodelling is a tightly-coordinated and lifelong process of replacing old damaged bone with newly-synthesized healthy bone. In the bone remodelling cycle, bone resorption is coupled with bone formation to maintain the bone volume and microarchitecture. This process is a result of communication between bone cells (osteoclasts, osteoblasts, and osteocytes) with paracrine and endocrine regulators, such as cytokines, reactive oxygen species, growth factors, and hormones. The essential signalling pathways responsible for osteoclastic bone resorption and osteoblastic bone formation include the receptor activator of nuclear factor kappa-B (RANK)/receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG), Wnt/β-catenin, and oxidative stress signalling. The imbalance between bone formation and degradation, in favour of resorption, leads to the occurrence of osteoporosis. Intriguingly, vitamin E has been extensively reported for its anti-osteoporotic properties using various male and female animal models. Thus, understanding the underlying cellular and molecular mechanisms contributing to the skeletal action of vitamin E is vital to promote its use as a potential bone-protecting agent. This review aims to summarize the current evidence elucidating the molecular actions of vitamin E in regulating the bone remodelling cycle.
Fulltext Proton Pump Inhibitors and Fracture Risk: A Review of Current Evidence and Mechanisms Involved

Thong BKS, Ima-Nirwana S, Chin KY

Int J Environ Res Public Health, 2019 May 05;16(9).
PMID: 31060319 DOI: 10.3390/ijerph16091571

The number of patients with gastroesophageal problems taking proton pump inhibitors (PPIs) is increasing. Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. This review aimed to investigate the longitudinal studies published in the last five years on the relationship between PPIs and fracture risk. The mechanism underlying this relationship was also explored. Overall, PPIs were positively associated with elevated fracture risk in multiple studies (n = 14), although some studies reported no significant relationship (n = 4). Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, mineral absorption, and muscle strength, contributing to increased fracture risk among PPI users. As a conclusion, there is a potential relationship between PPIs and fracture risks. Therefore, patients on long-term PPI treatment should pay attention to bone health status and consider prophylaxis to decrease fracture risk.
Fulltext Prostate Cancer and Bone Metastases: The Underlying Mechanisms

Wong SK, Mohamad NV, Giaze TR, Chin KY, Mohamed N, Ima-Nirwana S

Int J Mol Sci, 2019 May 27;20(10).
PMID: 31137764 DOI: 10.3390/ijms20102587

Patients with advanced prostate cancer often develop bone metastases, leading to bone pain, skeletal fracture, and increased mortality. Bone provides a hospitable microenvironment to tumor cells. The disease manifestation is driven by the interaction between invading tumor cells, bone-forming osteoblasts, and bone-resorbing osteoclasts. The increased level of osteoclast-activating factor (parathyroid hormone-related peptide, PTHrP) is believed to induce bone resorption by upregulating receptor activator of nuclear factor-kappa B ligand (RANKL) and the release of various growth factors into the bone microenvironment to enhance cancer cell growth. However, the underlying molecular mechanisms remain poorly understood. This review outlines the possible molecular mechanisms involved in governing bone metastases driven by prostate cancer, which further provide the basis in searching for new molecular targets for the development of potential therapy.
The relationship between circulating testosterone and inflammatory cytokines in men

Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima-Nirwana S, et al.

Aging Male, 2019 Jun;22(2):129-140.
PMID: 29925283 DOI: 10.1080/13685538.2018.1482487

Testosterone is the predominant gonadal androgen in men. Low testosterone levels are found to be associated with an increased in metabolic risk and systematic inflammation. Since adipose tissue is a source of inflammatory cytokines, testosterone may regulate inflammation by acting on adipose tissue. This review aimed to explore the role of testosterone in inflammation and its mechanism of action. Both animal studies and human studies showed that (1) testosterone deficiency was associated with an increase in pro-inflammatory cytokines; (2) testosterone substitution reduced pro-inflammatory cytokines. The suppression of inflammation by testosterone were observed in patients with coronary artery disease, prostate cancer and diabetes mellitus through the increase in anti-inflammatory cytokines (IL-10) and the decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Despite these, some studies also reported a non-significant relationship. In conclusion, testosterone may possess anti-inflammatory properties but its magnitude is debatable. More evidence is needed to validate the use of testosterone as a marker and in the management of chronic inflammatory diseases.
The use of selective estrogen receptor modulators on bone health in men

Wong SK, Mohamad NV, Jayusman PA, Shuid AN, Ima-Nirwana S, Chin KY

Aging Male, 2019 Jun;22(2):89-101.
PMID: 29508640 DOI: 10.1080/13685538.2018.1448058

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.
Fulltext The Effects of Annatto Tocotrienol Supplementation on Cartilage and Subchondral Bone in an Animal Model of Osteoarthritis Induced by Monosodium Iodoacetate

Chin KY, Wong SK, Japar Sidik FZ, Abdul Hamid J, Abas NH, Mohd Ramli ES, et al.

Int J Environ Res Public Health, 2019 08 13;16(16).
PMID: 31412648 DOI: 10.3390/ijerph16162897

Osteoarthritis is a degenerative joint disease which primarily affects the articular cartilage and subchondral bones. Since there is an underlying localized inflammatory component in the pathogenesis of osteoarthritis, compounds like tocotrienol with anti-inflammatory properties may be able to retard its progression. This study aimed to determine the effects of oral tocotrienol supplementation on the articular cartilage and subchondral bone in a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). Thirty male Sprague-Dawley rats (three-month-old) were randomized into five groups. Four groups were induced with osteoarthritis (single injection of MIA at week 0) and another served as the sham group. Three of the four groups with osteoarthritis were supplemented with annatto tocotrienol at 50, 100 and 150 mg/kg/day orally for five weeks. At week 5, all rats were sacrificed, and their tibial-femoral joints were harvested for analysis. The results indicated that the groups which received annatto tocotrienol at 100 and 150 mg/kg/day had lower histological scores and cartilage remodeling markers. Annatto tocotrienol at 150 mg/kg/day significantly lowered the osteocalcin levels and osteoclast surface of subchondral bone. In conclusion, annatto tocotrienol may potentially retard the progression of osteoarthritis. Future studies to confirm its mechanism of joint protection should be performed.
Fulltext The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells

Wong SK, Chin KY, Ima-Nirwana S

Int J Environ Res Public Health, 2019 09 09;16(18).
PMID: 31505801 DOI: 10.3390/ijerph16183313

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.
Fulltext Levels of Knowledge, Beliefs, and Practices Regarding Osteoporosis and the Associations with Bone Mineral Density among Populations More Than 40 Years Old in Malaysia

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.
Fulltext The effects of annatto tocotrienol on body composition and serum adiponectin, leptin and glucose level in a rat model of androgen deficiency induced by Buserelin

Mohamad, N.V., Ima-Nirwana, S., Chin, K.Y.

Medicine & Health, 2019;14(2):168-179.
MyJurnal

Androgen ablation therapy using gonadotropin-releasing hormone agonists is reported to be associated with metabolic abnormalities. Annatto tocotrienol (AnTT) is reported to reduce the expression of genes related to adipogenesis but the mechanism remains elusive. This study sought to determine the effects of annatto tocotrienol on body composition (lean and fat mass), serum adiponectin, leptin, and glucose levels in male rats treated with buserelin, a testosterone ablation agent. Three-month-old male Sprague Dawley rats (n=32) were randomly divided into four groups. The normal control (n=8) was given corn oil orally daily and normal saline subcutaneously daily. The remaining groups were injected with buserelin subcutaneously (75μg/kg/day). The buserelin group (n=8) was given corn oil orally, while the treatment groups were supplemented orally with AnTT at 60 or 100 mg/ kg (n = 8/group). After treatment of 12 weeks, rats were euthanized. Dual-energy x-ray absorptiometry was performed to determine the lean and fat mass of the rats. Blood was collected for the evaluation of adiponectin, leptin and glucose levels. After 12 weeks, the lean mass, fat mass, adiponectin and leptin levels for all groups increased significantly compared to their respective baseline levels irrespective of their treatment (P
Toll-like Receptor as a Molecular Link between Metabolic Syndrome and Inflammation: A Review

Wong SK, Chin KY, Ima-Nirwana S

Curr Drug Targets, 2019;20(12):1264-1280.
PMID: 30961493 DOI: 10.2174/1389450120666190405172524

Metabolic Syndrome (MetS) involves a cluster of five conditions, i.e. obesity, hyperglycaemia, hypertension, hypertriglyceridemia and low High-Density Lipoprotein (HDL) cholesterol. All components of MetS share an underlying chronic inflammatory aetiology, manifested by increased levels of pro-inflammatory cytokines. The pathogenic role of inflammation in the development of MetS suggested that toll-like receptor (TLR) activation may trigger MetS. This review summarises the supporting evidence on the interactions between MetS and TLR activation, bridged by the elevation of TLR ligands during MetS. The regulatory circuits mediated by TLR activation, which modulates signal propagation, leading to the state of chronic inflammation, are also discussed. Taken together, TLR activation could be the molecular basis in the development of MetS-induced inflammation.
Fulltext The Osteoprotective Effects Of Kaempferol: The Evidence From In Vivo And In Vitro Studies

Wong SK, Chin KY, Ima-Nirwana S

Drug Des Devel Ther, 2019;13:3497-3514.
PMID: 31631974 DOI: 10.2147/DDDT.S227738

Kaempferol is a dietary bioflavonoid ubiquitously found in various types of plant. It possesses a wide range of medicinal properties suggesting its potential clinical utility that requires further investigation. The present review intends to highlight the efficacy of kaempferol and its molecular mechanisms of action in regulating bone metabolism. Many reports have acknowledged the bone-protecting property of kaempferol and kaempferol-containing plants using in vitro and in vivo experimental models. Kaempferol supplementation showed bone-sparing effects in newborn rats, glucocorticoid-induced and ovariectomy-induced osteoporotic models as well as bone fracture models. It achieves the bone-protective effects by inhibiting adipogenesis, inflammation, oxidative stress, osteoclastic autophagy and osteoblastic apoptosis while activating osteoblastic autophagy. The anti-osteoporotic effects of kaempferol are mediated through regulation of estrogen receptor, bone morphogenetic protein-2 (BMP-2), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways. In summary, kaempferol exhibits beneficial effects on skeleton, thus is potentially effective for the prophylaxis and treatment of osteoporosis.
Berberine and musculoskeletal disorders: The therapeutic potential and underlying molecular mechanisms

Wong SK, Chin KY, Ima-Nirwana S

Phytomedicine, 2020 Jul 15;73:152892.
PMID: 30902523 DOI: 10.1016/j.phymed.2019.152892

BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders.
PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.
METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.
RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.
CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.
Biochemical and histopathological assessment of liver in a rat model of metabolic syndrome induced by high-carbohydrate high-fat diet

Wong SK, Chin KY, Ahmad F, Ima-Nirwana S

J Food Biochem, 2020 Aug 03.
PMID: 32744348 DOI: 10.1111/jfbc.13371

This study aimed to evaluate the oxidative stress status, antioxidants capacity, and presence of nonalcoholic fatty liver disease (NAFLD) in an animal model of MetS induced by high-carbohydrate high-fat (HCHF) diet. Male Wistar rats were randomized into two groups, assigned for two different types of diet (standard rat pellet or HCHF diet) for 20 weeks. Liver was excised, weighed, and subjected to lipid peroxidation, nitric oxide (NO·) production, antioxidants activity, and histological assessment. The HCHF rats had higher lipid peroxidation and NO· level but lower enzymatic and nonenzymatic antioxidant levels than the normal animals. Histological evaluation revealed higher lobular inflammation, hepatocellular ballooning, NAFLD activity score, and lipid accumulation in the liver of HCHF group. In conclusion, the HCHF diet causes an increase in oxidative stress, depletion of antioxidants capacity, NAFLD, and liver injury. The induction of oxidative stress may be partially responsible for the development of NAFLD in MetS. PRACTICAL APPLICATIONS: The prevalence of MetS is estimated to increase rapidly with the escalating levels of obesity, diabetes, hypertension, and dyslipidemia. A suitable animal model of MetS that best mimicked the human disease state with known underlying mechanisms responsible for the pathogenesis of MetS is indispensable to search for potential adjunct therapies and drug targets. Thus, our current study elucidated the involvement of oxidative stress in linking MetS and NAFLD which might resemble the pathogenesis of MetS among Southeast Asian population.
Fulltext Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence

Wong SK, Chin KY, Ima-Nirwana S

Int J Mol Sci, 2020 Sep 03;21(17).
PMID: 32899435 DOI: 10.3390/ijms21176448

Quercetin is a flavonoid abundantly found in fruits and vegetables. It possesses a wide spectrum of biological activities, thus suggesting a role in disease prevention and health promotion. The present review aimed to uncover the bone-sparing effects of quercetin and its mechanism of action. Animal studies have found that the action of quercetin on bone is largely protective, with a small number of studies reporting negative outcomes. Quercetin was shown to inhibit RANKL-mediated osteoclastogenesis, osteoblast apoptosis, oxidative stress and inflammatory response while promoting osteogenesis, angiogenesis, antioxidant expression, adipocyte apoptosis and osteoclast apoptosis. The possible underlying mechanisms involved are regulation of Wnt, NF-κB, Nrf2, SMAD-dependent, and intrinsic and extrinsic apoptotic pathways. On the other hand, quercetin was shown to exert complex and competing actions on the MAPK signalling pathway to orchestrate bone metabolism, resulting in both stimulatory and inhibitory effects on bone in parallel. The overall interaction is believed to result in a positive effect on bone. Considering the important contributions of quercetin in regulating bone homeostasis, it may be considered an economical and promising agent for improving bone health. The documented preclinical findings await further validation from human clinical trials.
Prevalence and factors of T-score discordance between hip and spine among middle-aged and elderly Malaysians

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.

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