Displaying publications 21 - 40 of 165 in total

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  1. 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.
  2. Ramli FF, Chin KY
    Diagnostics (Basel), 2020 Mar 06;10(3).
    PMID: 32155909 DOI: 10.3390/diagnostics10030145
    Bone turnover markers (BTMs) derived from the secretory activities of osteoblasts and the matrix-degrading activities of osteoclasts are useful in monitoring the progression of osteoporosis and the efficacy of anti-osteoporotic treatment. However, the usefulness of BTMs in predicting osteoporosis remains elusive. Osteocytes play a central role in regulating bone formation and resorption. The proteins secreted by osteocytes, such as fibroblast growth factor-23 (FGF23), sclerostin (SOST), and dickkopf-1 (DKK1), could be candidates for osteoporosis screening and fracture prediction. This review summarizes the current evidence on the potential of osteocyte-related proteins as biomarkers for osteoporosis and fracture prediction. The literature reports that SOST may be a potential marker for osteoporosis screening but not for fracture prediction. FGF23 is a potential marker for increased fracture risk, but more studies are needed to confirm its usefulness. The role of DKK1 as a marker to predict osteoporosis and fracture risk cannot be confirmed due to a lack of consistent evidence. In conclusion, circulating osteocyte markers are potential osteoporosis biomarkers, but more studies are warranted to validate their clinical use.
  3. Chin KY, Ima-Nirwana S
    PMID: 27472350 DOI: 10.3390/ijerph13080755
    Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly.
  4. Chin KY, Ima-Nirwana S
    Int J Endocrinol Metab, 2017 Jan;15(1):e43053.
    PMID: 28835763 DOI: 10.5812/ijem.43053
    BACKGROUND: Testosterone deficiency is linked to low-grade inflammation in humans, but this condition is not replicated in an animal study. The current study aims at determining the effects of testosterone deficiency and its replacement on the circulating inflammatory cytokine level in orchidectomized male rats.

    METHODS: Three-month-old Sprague-Dawley male rats (n = 18) were randomized equally into 3 groups. Bilateral orchidectomy was performed on 2 groups. The sham group was subjected to similar surgical stress, but their testes were retained. One of the orchidectomized groups received intramuscular injection of 7 mg/kg testosterone enanthate suspended in peanut oil weekly and the other 2 groups received equivolume of peanut oil injection. After 8 weeks, the rats were sacrificed and their blood was collected for the analysis of the levels of inflammatory cytokines and testosterone.

    RESULTS: Testosterone level was significantly lower in the untreated orchidectomized group compared to the sham group. Testosterone replacement significantly increased the level of testosterone in the orchidectomized rats compared to the sham and untreated orchidectomized rats. Interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα) showed an increasing trend in orchidectomized rats, albeit not statistically significant. Interleukin-6 (IL-6) level increased significantly in the orchidectomized group compared to the sham group. Testosterone replacement at the supraphysiological dose did not alter the level of inflammatory cytokines significantly in orchidectomized rats.

    CONCLUSIONS: Testosterone deficiency can elicit a state of low-grade inflammation, shown by an increase in interleukin-6 level, but exogenous supraphysiological testosterone replacement does not suppress the inflammation.

  5. Chin KY, Pang KL
    Nutrients, 2017 Sep 26;9(10).
    PMID: 28954409 DOI: 10.3390/nu9101060
    Osteoarthritis is a major cause of morbidity among the elderly worldwide. It is a disease characterized by localized inflammation of the joint and destruction of cartilage, leading to loss of function. Impaired chondrocyte repair mechanisms, due to inflammation, oxidative stress and autophagy, play important roles in the pathogenesis of osteoarthritis. Olive and its derivatives, which possess anti-inflammatory, antioxidant and autophagy-enhancing activities, are suitable candidates for therapeutic interventions for osteoarthritis. This review aimed to summarize the current evidence on the effects of olive and its derivatives, on osteoarthritis and chondrocytes. The literature on animal and human studies has demonstrated a beneficial effect of olive and its derivatives on the progression of osteoarthritis. In vitro studies have suggested that the augmentation of autophagy (though sirtuin-1) and suppression of inflammation by olive polyphenols could contribute to the chondroprotective effects of olive polyphenols. More research and well-planned clinical trials are required to justify the use of olive-based treatment in osteoarthritis.
  6. Pang KL, Chin KY
    Int J Mol Sci, 2019 Oct 25;20(21).
    PMID: 31731474 DOI: 10.3390/ijms20215318
    Selenium is a trace element essential to humans and forms complexes with proteins, which exert physiological functions in the body. In vitro studies suggested that selenium possesses anticancer effects and may be effective against osteosarcoma. This review aims to summarise current evidence on the anticancer activity of inorganic and organic selenium on osteosarcoma. Cellular studies revealed that inorganic and organic selenium shows cytotoxicity, anti-proliferative and pro-apoptotic effects on various osteosarcoma cell lines. These actions may be mediated by oxidative stress induced by selenium compounds, leading to the activation of p53, proapoptotic proteins and caspases. Inorganic selenium is selective towards cancer cells, but can cause non-selective cell death at a high dose. This condition challenges the controlled release of selenium from biomaterials. Selenium treatment in animals inoculated with osteosarcoma reduced the tumour size, but did not eliminate the incidence of osteosarcoma. Only one study investigated the relationship between selenium and osteosarcoma in humans, but the results were inconclusive. In summary, although selenium may exert anticancer properties on osteosarcoma in experimental model systems, its effects in humans require further investigation.
  7. Chin KY, Ima-Nirwana S
    Int J Endocrinol, 2012;2012:208719.
    PMID: 23150727 DOI: 10.1155/2012/208719
    Male osteoporosis is a health problem which deserves more attention as nearly 30% of osteoporotic fractures happen in men aged 50 years and above. Although men do not experience an accelerated bone loss phase and testosterone deficiency is not a universal characteristic for aged men, osteoporosis due to age-related testosterone deficiency does have a negative impact on bone health status of men. Observations from epidemiological studies indicate that elderly men with higher testosterone can preserve their BMD better and thus are less prone to fracture. Observations on men with estrogen resistance or aromatase deficiency indicate that estrogen is equally important in the maintenance of bone health status. This had been validated in several epidemiological studies which found that the relationships between estrogen and bone health indices are significant and sometimes stronger than testosterone. Studies on the relationship between quantitative ultrasound and bone remodeling markers suggest that testosterone and estrogen may have differential effects on bone, but further evidence was needed. In conclusion, both testosterone and estrogen are important in the maintenance of bone health in men.
  8. Ekeuku SO, Chin KY
    Molecules, 2021 May 25;26(11).
    PMID: 34070497 DOI: 10.3390/molecules26113156
    Chronic inflammation and oxidative stress are two major mechanisms leading to the imbalance between bone resorption and bone formation rate, and subsequently, bone loss. Thus, functional foods and dietary compounds with antioxidant and anti-inflammatory could protect skeletal health. This review aims to examine the current evidence on the skeletal protective effects of propolis, a resin produced by bees, known to possess antioxidant and anti-inflammatory activities. A literature search was performed using Pubmed, Scopus, and Web of Science to identify studies on the effects of propolis on bone health. The search string used was (i) propolis AND (ii) (bone OR osteoporosis OR osteoblasts OR osteoclasts OR osteocytes). Eighteen studies were included in the current review. The available experimental studies demonstrated that propolis could prevent bone loss due to periodontitis, dental implantitis, and diabetes in animals. Combined with synthetic and natural grafts, it could also promote fracture healing. Propolis protects bone health by inhibiting osteoclastogenesis and promoting osteoblastogenesis, partly through its antioxidant and anti-inflammatory actions. Despite the promising preclinical results, the skeletal protective effects of propolis are yet to be proven in human studies. This research gap should be bridged before nutraceuticals based on propolis with specific health claims can be developed.
  9. Pang KL, Chin KY
    Nutrients, 2018 May 06;10(5).
    PMID: 29734791 DOI: 10.3390/nu10050570
    Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies.
  10. Chin KY, Ima-Nirwana S
    PMID: 22919420 DOI: 10.1155/2012/747020
    Osteoporosis is a growing healthcare burden that affects the quality of life in the aging population. Vitamin E is a potential prophylactic agent that can impede the progression of osteoporosis. Various in vivo studies demonstrated the antiosteoporotic potential of vitamin E, but evidence on its molecular mechanism of action is limited. A few in vitro studies showed that various forms of vitamin E can affect the receptor activator of nuclear factor kappa-B ligand (RANKL) signaling and their molecular targets, thus preventing the formation of osteoclasts in the early stage of osteoclastogenesis. Various studies have also shown that the effects of the different isoforms of vitamin E differ. The effects of single isoforms and combinations of isoforms on bone metabolism are also different. Vitamin E may affect bone metabolism by disruption of free radical-mediated RANKL signaling, by its oestrogen-like effects, by its effects on the molecular mechanism of bone formation, by the anti-inflammatory effects of its long-chain metabolites on bone cells, and by the inhibition of 3-hydroxyl-3-methyglutaryl coenzyme A (HMG-CoA). In conclusion, the vitamin E isoforms have enormous potential to be used as prophylactic and therapeutic agents in preventing osteoporosis, but further studies should be conducted to elucidate their mechanisms of action.
  11. Chin KY, Mo H, Soelaiman IN
    Curr Drug Targets, 2013 Dec;14(13):1533-41.
    PMID: 23859472
    Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/β-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.
  12. Hafiz A, Ima-Nirwana S, Chin KY
    J Taibah Univ Med Sci, 2018 Oct;13(5):491-495.
    PMID: 31435368 DOI: 10.1016/j.jtumed.2018.01.004
    Objectives: Physicians are known to experience a high level of stress due to the profession itself, as well as due to factors related to the workplace, patient care, and work-life balance. Owing to the nature of public and private hospitals in Malaysia, physicians working in different settings are expected to have different levels of stress. However, there is no study to validate this assumption. The present study aimed to compare stress levels between physicians working in public and private hospitals in the state of Johor, Malaysia.

    Methods: Participants were selected via stratified sampling. Participants completed an online questionnaire comprising demographic details and the Health Professional Stress Inventory. Scores on each domain and the aggregate scores were compared between physicians in public and private hospitals using a univariate analysis adjusted for potential confounders.

    Results: The overall stress level between physicians in public and private hospitals was similar. However, physicians in private hospitals experienced a higher stress level related to patient care responsibilities and professional uncertainty as compared to those in public hospitals.

    Conclusion: Physicians from private hospitals experience stress in different aspects of their profession as compared to physicians in public hospitals, especially with reference to patient care and career uncertainty. Measures should be taken to relieve the stress of physicians and thus improve their wellbeing.

  13. Wong SK, Chin KY, Ima-Nirwana S
    Int J Med Sci, 2020;17(11):1625-1638.
    PMID: 32669965 DOI: 10.7150/ijms.47103
    Oxidative stress and inflammation are two interlinked events that exist simultaneously in metabolic syndrome (MetS) and its related complications. These pathophysiological processes can be easily triggered by each other. This review summarizes the current evidence from animal and human studies on the effects of vitamin C in managing MetS. In vivo studies showed promising effects of vitamin C, but most of the interventions used were in combination with other compounds. The direct effects of vitamin C remain to be elucidated. In humans, the current state of evidence revealed that lower vitamin C intake and circulating concentration were found in MetS subjects. A negative relationship was observed between vitamin C intake / concentration and the risk of MetS. Oral supplementation of vitamin C also improved MetS conditions. It has been postulated that the positive outcomes of vitamin C may be in part mediated through its anti-oxidative and anti-inflammatory properties. These observations suggest the importance of MetS patients to have an adequate intake of vitamin C through food, beverages or supplements in order to maintain its concentration in the systemic circulation and potentially reverse MetS.
  14. 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.
  15. 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.
  16. Pang KL, Lumintang JN, Chin KY
    Nutrients, 2021 Feb 06;13(2).
    PMID: 33561976 DOI: 10.3390/nu13020529
    Olive oil, which is commonly used in the Mediterranean diet, is known for its health benefits related to the reduction of the risks of cancer, coronary heart disease, hypertension, and neurodegenerative disease. These unique properties are attributed to the phytochemicals with potent antioxidant activities in olive oil. Olive leaf also harbours similar bioactive compounds. Several studies have reported the effects of olive phenolics, olive oil, and leaf extract in the modulation of thyroid activities. A systematic review of the literature was conducted to identify relevant studies on the effects of olive derivatives on thyroid function. A comprehensive search was conducted in October 2020 using the PubMed, Scopus, and Web of Science databases. Cellular, animal, and human studies reporting the effects of olive derivatives, including olive phenolics, olive oil, and leaf extracts on thyroid function were considered. The literature search found 445 articles on this topic, but only nine articles were included based on the inclusion and exclusion criteria. All included articles were animal studies involving the administration of olive oil, olive leaf extract, or olive pomace residues orally. These olive derivatives were consistently demonstrated to have thyroid-stimulating activities in euthyroid or hypothyroid animals, but their mechanisms of action are unknown. Despite the positive results, validation of the beneficial health effects of olive derivatives in the human population is lacking. In conclusion, olive derivatives, especially olive oil and leaf extract, could stimulate thyroid function. Olive pomace residue is not suitable for pharmaceutical or health supplementation purposes. Therapeutic applications of olive oil and leaf extract, especially in individuals with hypothyroidism, require further validation through human studies.
  17. Ekeuku SO, Pang KL, Chin KY
    Molecules, 2021 Apr 16;26(8).
    PMID: 33923673 DOI: 10.3390/molecules26082319
    BACKGROUND: Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of Salvia miltiorrhiza with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. This systematic review aims to provide an overview of the skeletal beneficial effects of tanshinones.

    METHODS: A systematic literature search was conducted in January 2021 using Pubmed, Scopus and Web of Science from the inception of these databases. Original studies reporting the effects of tanshinones on bone through cell cultures, animal models and human clinical trials were considered.

    RESULTS: The literature search found 158 unique articles on this topic, but only 20 articles met the inclusion criteria and were included in this review. The available evidence showed that tanshinones promoted osteoblastogenesis and bone formation while reducing osteoclastogenesis and bone resorption.

    CONCLUSIONS: Tanshinones modulates bone remodelling by inhibiting osteoclastogenesis and osteoblast apoptosis and stimulating osteoblastogenesis. Therefore, it might complement existing strategies to prevent bone loss.

  18. Hashim KN, Chin KY, Ahmad F
    Molecules, 2021 Feb 04;26(4).
    PMID: 33557218 DOI: 10.3390/molecules26040808
    Metabolic syndrome is a constellation of five risk factors comprising central obesity, hyperglycaemia, dyslipidaemia, and hypertension, which predispose a person to cardiometabolic diseases. Many studies reported the beneficial effects of honey in reversing metabolic syndrome through its antiobesity, hypoglycaemic, hypolipidaemic, and hypotensive actions. This review aims to provide an overview of the mechanism of honey in reversing metabolic syndrome. The therapeutic effects of honey largely depend on the antioxidant and anti-inflammatory properties of its polyphenol and flavonoid contents. Polyphenols, such as caffeic acid, p-coumaric acid, and gallic acid, are some of the phenolic acids known to have antiobesity and antihyperlipidaemic properties. They could inhibit the gene expression of sterol regulatory element-binding transcription factor 1 and its target lipogenic enzyme, fatty acid synthase (FAS). Meanwhile, caffeic acid and quercetin in honey are also known to reduce body weight and fat mass. In addition, fructooligosaccharides in honey are also known to alter lipid metabolism by reducing FAS activity. The fructose and phenolic acids might contribute to the hypoglycaemic properties of honey through the phosphatidylinositol 3-kinase/protein kinase B insulin signalling pathway. Honey can increase the expression of Akt and decrease the expression of nuclear factor-kappa B. Quercetin, a component of honey, can improve vasodilation by enhancing nitric oxide production via endothelial nitric oxide synthase and stimulate calcium-activated potassium channels. In conclusion, honey can be used as a functional food or adjuvant therapy to prevent and manage metabolic syndrome.
  19. Wong SK, Ima-Nirwana S, Chin KY
    Bosn J Basic Med Sci, 2020 Nov 02;20(4):423-429.
    PMID: 32156247 DOI: 10.17305/bjbms.2020.4664
    Telomeres are repetitive DNA sequences located at the end of chromosomes that serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50-200 base pairs of nucleotides are lost per cell division, and new repetitive nucleotides are added by the enzyme telomerase, allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological aging, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase of bone cells to treat osteoporosis.
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