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Fulltext Skeletal Effects of Early-Life Exposure to Soy Isoflavones-A Review of Evidence From Rodent Models

Chin KY, Pang KL

Front Pediatr, 2020;8:563.
PMID: 33072660 DOI: 10.3389/fped.2020.00563

Isoflavones are dietary phytoestrogens commonly found in soy-based products. The widespread presence of isoflavones in soy infant formula and breast milk may have long-lasting effects on the development of sex hormone-sensitive organs like the skeleton. Animal early-life programming models are suitable for testing the skeletal effects of pre- and neonatal exposure of soy isoflavones. This review aims to collate the impacts of early-life exposure of soy isoflavones as evidenced in animal models. The isoflavones previously studied include daidzein, genistein, or a combination of both. They were administered to rodent pups during the first few days postnatal, but prolonged exposure had also been studied. The skeletal effects were observed when the animals reached sexual maturity or after castration to induce bone loss. In general, neonatal exposure to soy isoflavones exerted beneficial effects on the skeletal system of female rodents, but the effects on male rodents seem to depend on the time of exposure and require further examinations. It might also protect the animals against bone loss due to ovariectomy at adulthood but not upon orchidectomy. The potential benefits of isoflavones on the skeletal system should be interpreted together with its non-skeletal effects in the assessment of its safety and impacts.
Fulltext Comment on: Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration. Int. J. Mol. Sci. 2020, 21, 4661

Pang KL, Chin KY

Int J Mol Sci, 2020 09 12;21(18).
PMID: 32932718 DOI: 10.3390/ijms21186674

Dear Editor, [...].
Fulltext The Role of Tocotrienol in Protecting Against Metabolic Diseases

Pang KL, Chin KY

Molecules, 2019 Mar 06;24(5).
PMID: 30845769 DOI: 10.3390/molecules24050923

Obesity is a major risk factor for diabetes, and these two metabolic conditions cause significant healthcare burden worldwide. Chronic inflammation and increased oxidative stress due to exposure of cells to excess nutrients in obesity may trigger insulin resistance and pancreatic β-cell dysfunction. Tocotrienol, as a functional food component with anti-inflammatory, antioxidant, and cell signaling-mediating effects, may be a potential agent to complement the current management of obesity and diabetes. The review aimed to summarize the current evidence on the anti-obesity and antidiabetic effects of tocotrienol. Previous studies showed that tocotrienol could suppress adipogenesis and, subsequently, reduce body weight and fat mass in animals. This was achieved by regulating pathways of lipid metabolism and fatty acid biosynthesis. It could also reduce the expression of transcription factors regulating adipogenesis and increase apoptosis of adipocytes. In diabetic models, tocotrienol was shown to improve glucose homeostasis. Activation of peroxisome proliferator-activated receptors was suggested to be responsible for these effects. Tocotrienol also prevented multiple systemic complications due to obesity and diabetes in animal models through suppression of inflammation and oxidative stress. Several clinical trials have been conducted to validate the antidiabetic of tocotrienol, but the results were heterogeneous. There is no evidence showing the anti-obesity effects of tocotrienol in humans. Considering the limitations of the current studies, tocotrienol has the potential to be a functional food component to aid in the management of patients with obesity and diabetes.
Fulltext Therapeutic Effects of Olive and Its Derivatives on Osteoarthritis: From Bench to Bedside

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.
Fulltext Emerging Anticancer Potentials of Selenium on Osteosarcoma

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.
Fulltext The Biological Activities of Oleocanthal from a Molecular Perspective

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.
Fulltext Thyroid-Modulating Activities of Olive and Its Polyphenols: A Systematic Review

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.
Fulltext The Skeletal Effects of Tanshinones: A Review

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.
Fulltext A Review on the Role of Denosumab in Fracture Prevention

Pang KL, Low NY, Chin KY

Drug Des Devel Ther, 2020;14:4029-4051.
PMID: 33061307 DOI: 10.2147/DDDT.S270829

Denosumab is a receptor activator of nuclear factor kappa-Β ligand inhibitor, which suppresses the bone resorption process to preserve bone mass. It is usually recommended to postmenopausal women and men with high fracture risk. With the recent publication of the results from FREEDOM study and its extension, the long-term effect of denosumab in preventing fragility fractures has been put forward. This review aims at summarising the evidence of denosumab in reducing fracture risk and its safety derived from clinical studies. Most of the evidence are derived from FREEDOM trials up to 10 years of exposure. Denosumab is reported to prevent vertebral and non-vertebral fractures. It is also proven effective in Japanese women, patients with chronic kidney diseases and breast cancer patients receiving antineoplastic therapy. Denosumab discontinuation leads to high remodeling, loss of bone mineral density and increased fracture risk. These negative effects might be preventable by bisphosphonate treatment. The safety profile of denosumab is consistent with increased years of exposure. In conclusion, denosumab is a safe and effective option for reducing fracture risk among patients with osteoporosis.
Tocotrienol and Its Role in Chronic Diseases

Chin KY, Pang KL, Soelaiman IN

Adv Exp Med Biol, 2016;928:97-130.
PMID: 27671814

Tocotrienol is a member of vitamin E family and is well-known for its antioxidant and anti-inflammatory properties. It is also a suppressor of mevalonate pathway responsible for cholesterol and prenylated protein synthesis. This review aimed to discuss the health beneficial effects of tocotrienol, specifically in preventing or treating hyperlipidaemia, diabetes mellitus, osteoporosis and cancer with respect to these properties. Evidence from in vitro, in vivo and human studies has been examined. It is revealed that tocotrienol shows promising effects in preventing or treating the health conditions previously mentioned in in vivo and in vitro models. In some cases, alpha-tocopherol attenuates the biological activity of tocotrienol. Except for its cholesterol-lowering effects, data on the health-promoting effects of tocotrienol in human are limited. As a conclusion, the encouraging results on the health beneficial effects of tocotrienol should motivate researchers to explore its potential use in human.
Fulltext Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review

Ekeuku SO, Pang KL, Chin KY

Drug Des Devel Ther, 2020;14:4963-4974.
PMID: 33235437 DOI: 10.2147/DDDT.S280520

Palmatine is a naturally occurring isoquinoline alkaloid with various pharmacological properties. Given its antioxidant and anti-inflammatory properties, palmatine may be able to impede the effects of metabolic syndrome (MetS) and its related diseases triggered by inflammation and oxidative stress. This review summarises the existing literature about the effects of palmatine supplementation on MetS and its complications. The evidence shows that palmatine could protect against MetS, and cardiovascular diseases, osteoporosis and osteoarthritis, which might be associated with MetS. These protective effects are mediated by the antioxidant and anti-inflammatory properties of palmatine. Although preclinical experiments have demonstrated the efficacy of palmatine against MetS and its related diseases, no human clinical trials have been performed to validate these effects. This research gap should be bridged to validate the efficacy and safety of palmatine supplementation in protecting humans against MetS and its related diseases.
Immunomodulatory Effects of Agarwood Leaf Extract on RAW264.7 Murine Macrophages

Pang KL, Chin KY, Nirwana SI

Endocr Metab Immune Disord Drug Targets, 2023;23(7):964-976.
PMID: 36597600 DOI: 10.2174/1871530323666230103153134

BACKGROUND: The immunomodulatory effects of plants have been utilised to enhance the immunity of humans against infections. However, evidence of such effects of agarwood leaves is very limited despite the long tradition of consuming the leaves as tea.
OBJECTIVE: This study aimed to investigate the immuno-modulatory effects of agarwood leaf extract (ALE) derived from Aquilaria malaccensis using RAW264.7 murine macrophages.
METHODS: In this study, RAW264.7 macrophages were incubated with ALE alone for 26 hours or ALE for 2 hours, followed by bacterial lipopolysaccharide for 24 hours. The nitrite and cytokine production (tumour necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, and IL-10), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) expression in the macrophages were assayed.
RESULTS: The study showed that ALE alone was immunostimulatory on the macrophages by increasing the nitrite, TNFα, and IL-6 production and COX2 expression (p<0.05 vs. untreated unstimulated cells). Pre-treatment of ALE suppressed nitrite level and iNOS expression but enhanced TNFα and IL-6 production and COX2 expression (p<0.05 vs. untreated lipopolysaccharides (LPS)-stimulated cells). ALE also increased IL-10 production regardless of LPS stimulation (p<0.05 vs. untreated cells).
CONCLUSION: ALE was able to promote the immune response of macrophages by upregulating pro-inflammatory cytokine levels and COX2 expression. It also regulated the extent of the inflammation by reducing iNOS expression and increasing IL-10 levels. Thus, ALE may have a role in enhancing the innate immune system against infection; however, its validation from in vivo studies is still pending.
Fulltext Particulate Air Pollution and Osteoporosis: A Systematic Review

Pang KL, Ekeuku SO, Chin KY

Risk Manag Healthc Policy, 2021;14:2715-2732.
PMID: 34194253 DOI: 10.2147/RMHP.S316429

Air pollution is associated with inflammation and oxidative stress, which predispose to several chronic diseases in human. Emerging evidence suggests that the severity and progression of osteoporosis are directly associated with inflammation induced by air pollutants like particulate matter (PM). This systematic review examined the relationship between PM and bone health or fractures. A comprehensive literature search was conducted from January until February 2021 using the PubMed, Scopus, Web of Science, Google Scholar and Cochrane Library databases. Human cross-sectional, cohort and case-control studies were considered. Of the 1500 papers identified, 14 articles were included based on the inclusion and exclusion criteria. The air pollution index investigated by most studies were PM2.5 and PM10. Current studies demonstrated inconsistent associations between PM and osteoporosis risk or fractures, which may partly due to the heterogeneity in subjects' characteristics, study design and analysis. In conclusion, there is an inconclusive relationship between osteoporosis risk and fracture and PM exposures which require further validation.
Fulltext Effects of Caffeic Acid and Its Derivatives on Bone: A Systematic Review

Ekeuku SO, Pang KL, Chin KY

Drug Des Devel Ther, 2021;15:259-275.
PMID: 33519191 DOI: 10.2147/DDDT.S287280

PURPOSE: Caffeic acid is a metabolite of hydroxycinnamate and phenylpropanoid, which are commonly synthesized by all plant species. It is present in various food sources that are known for their antioxidant properties. As an antioxidant, caffeic acid ameliorates reactive oxygen species, which have been reported to cause bone loss. Some studies have highlighted the effects of caffeic acid against bone resorption.
METHODS: A systematic review of the literature was conducted to identify relevant studies on the effects of caffeic acid on bone. A comprehensive search was conducted from July to November 2020 using PubMed, Scopus, Cochrane Library and Web of Science databases. Cellular, animal and human studies reporting the effects of caffeic acid, as a single compound, on bone cells or bone were considered.
RESULTS: The literature search found 226 articles on this topic, but only 24 articles met the inclusion criteria and were included in this review. The results showed that caffeic acid supplementation reduced osteoclastogenesis and bone resorption, possibly through its antioxidant potential and increased expression of osteoblast markers. However, some studies showed that caffeic acid did not affect bone resorption in ovariectomized rats and might impair bone mechanical properties in normal rats.
CONCLUSION: Caffeic acid potentially regulates the bone remodelling process by inhibiting osteoclastogenesis and bone resorption, as well as osteoblast apoptosis. Thus, it has medicinal values against bone diseases.
Fulltext A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

Chin KY, Pang KL, Mark-Lee WF

Int J Med Sci, 2018;15(10):1043-1050.
PMID: 30013446 DOI: 10.7150/ijms.25634

Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.
Fulltext Betulinic acid‑induced expression of nicotinamide adenine dinucleotide phosphate‑diaphorase in the immune organs of mice: A possible role of nitric oxide in immunomodulation

Pang KL, Vijayaraghavan K, Al Sayed B, Seyed MA

Mol Med Rep, 2018 Feb;17(2):3035-3041.
PMID: 29257292 DOI: 10.3892/mmr.2017.8262

The aim of the present study was to investigate the effects of betulinic acid (BetA) on the expression and distribution pattern of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‑d), an indirect indicator of nitric oxide (NO) synthase in the thymus and spleen of mice. Mice were randomly assigned to four main groups (n=48 per group): Experimental group (BetA), positive control group (goniothalamin), vehicle control group (dimethyl sulfoxide) and control group (without vehicle). Each group was further divided into three equal subgroups according to the treatment length (4, 8 and 12 days). BetA treatment induced the expression of NADPH‑d activity in the thymus and spleen without any significant changes in the morphology of the organs. Furthermore, the expression pattern of NADPH‑d in BetA‑treated animals was significantly increased compared with that in the control animals. NADPH‑d expression in the thymus and spleen suggests that NO signaling may be a potential mechanism underlying the BetA‑induced immunomodulation in these organs. These findings are of direct clinical relevance and may contribute to the further development of BetA as a therapeutic drug.
Fulltext Relationship Between Metabolic Syndrome and Bone Health - An Evaluation of Epidemiological Studies and Mechanisms Involved

Chin KY, Wong SK, Ekeuku SO, Pang KL

Diabetes Metab Syndr Obes, 2020;13:3667-3690.
PMID: 33116718 DOI: 10.2147/DMSO.S275560

Metabolic syndrome (MetS) and osteoporosis are two medical problems plaguing the ageing populations worldwide. Though seemingly distinctive to each other, metabolic derangements are shown to influence bone health. This review summarises the relationship between MetS and bone health derived from epidemiological studies and explains the mechanistic basis of this relationship. The discourse focuses on the link between MetS and bone mineral density, quantitative sonometric indices, geometry and fracture risk in humans. The interesting sex-specific trend in the relationship, probably due to factors related to body composition and hormonal status, is discussed. Mechanistically, each component of MetS affects the bone distinctly, forming a complex interacting network influencing the skeleton. Lastly, the effects of MetS management, such as pharmacotherapies, exercise and bariatric surgery, on bone, are presented. This review aims to highlight the significant relationship between MetS and bone, and proper management of MetS with the skeletal system in mind could prevent cardiovascular and bone complications.
Fulltext The Role of Tocotrienol in Arthritis Management-A Scoping Review of Literature

Tejpal Singh HS, Aminuddin AA, Pang KL, Ekeuku SO, Chin KY

Pharmaceuticals (Basel), 2023 Mar 02;16(3).
PMID: 36986484 DOI: 10.3390/ph16030385

Arthritis is a cluster of diseases impacting joint health and causing immobility and morbidity in the elderly. Among the various forms of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common. Currently, satisfying disease-modifying agents for arthritis are not available. Given the pro-inflammatory and oxidative stress components in the pathogenesis of arthritis, tocotrienol, a family of vitamin E with both anti-inflammatory and antioxidant properties, could be joint-protective agents. This scoping review aims to provide an overview of the effects of tocotrienol on arthritis derived from the existing scientific literature. A literature search using PubMed, Scopus and Web of Science databases was conducted to identify relevant studies. Only cell culture, animal and clinical studies with primary data that align with the objective of this review were considered. The literature search uncovered eight studies investigating the effects of tocotrienol on OA (n = 4) and RA (n = 4). Most of the studies were preclinical and revealed the positive effects of tocotrienol in preserving joint structure (cartilage and bone) in models of arthritis. In particular, tocotrienol activates the self-repair mechanism of chondrocytes exposed to assaults and attenuates osteoclastogenesis associated with RA. Tocotrienol also demonstrated strong anti-inflammatory effects in RA models. The single clinical trial available in the literature showcases that palm tocotrienol could improve joint function among patients with OA. In conclusion, tocotrienol could be a potential anti-arthritic agent pending more results from clinical studies.
Fulltext Establishing SW1353 Chondrocytes as a Cellular Model of Chondrolysis

Pang KL, Chow YY, Leong LM, Law JX, Ghafar NA, Soelaiman IN, et al.

Life (Basel), 2021 Mar 25;11(4).
PMID: 33805920 DOI: 10.3390/life11040272

Osteoarthritis (OA) is the most common degenerative joint disease characterised by chondrocyte cell death. An in vitro model of chondrocyte cell death may facilitate drug discovery in OA management. In this study, the cytotoxicity and mode of cell death of SW1353 chondrocytes treated with 24 h of OA inducers, including interleukin-1β (IL-1β), hydrogen peroxide (H2O2) and monosodium iodoacetate (MIA), were investigated. The microscopic features, oxidative (isoprostane) and inflammatory markers (tumour necrosis factor-alpha; TNF-α) for control and treated cells were compared. Our results showed that 24 h of H2O2 and MIA caused oxidative stress and a concentration-dependent reduction of SW1353 cell viability without TNF-α level upregulation. H2O2 primarily induced chondrocyte apoptosis with the detection of blebbing formation, cell shrinkage and cellular debris. MIA induced S-phase arrest on chondrocytes with a reduced number of attached cells but without significant cell death. On the other hand, 24 h of IL-1β did not affect the cell morphology and viability of SW1353 cells, with a significant increase in intracellular TNF-α levels without inducing oxidative stress. In conclusion, each OA inducer exerts differential effects on SW1353 chondrocyte cell fate. IL-1β is suitable in the inflammatory study but not for chondrocyte cell death. H2O2 and MIA are suitable for inducing chondrocyte cell death and growth arrest, respectively.
Fulltext Vitamin E in the management of pancreatic cancer: A scoping review

Ekeuku SO, Etim EP, Pang KL, Chin KY, Mai CW

World J Gastrointest Oncol, 2023 Jun 15;15(6):943-958.
PMID: 37389119 DOI: 10.4251/wjgo.v15.i6.943

Pancreatic cancer is the leading cause of cancer mortality worldwide. Research investigating effective management strategies for pancreatic cancer is ongoing. Vitamin E, consisting of both tocopherol and tocotrienol, has demonstrated debatable effects on pancreatic cancer cells. Therefore, this scoping review aims to summarize the effects of vitamin E on pancreatic cancer. In October 2022, a literature search was conducted using PubMed and Scopus since their inception. Original studies on the effects of vitamin E on pancreatic cancer, including cell cultures, animal models and human clinical trials, were considered for this review. The literature search found 75 articles on this topic, but only 24 articles met the inclusion criteria. The available evidence showed that vitamin E modulated proliferation, cell death, angiogenesis, metastasis and inflammation in pancreatic cancer cells. However, the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies. More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.

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