Effects of resveratrol on biochemical and structural outcomes in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

Background and objective: Osteoarthritis (OA) is the most common age-related disease of joints with increasing global prevalence. Persistent inflammation within the joint space is speculated to be the cause of OA. Resveratrol is an anti-inflammatory and antioxidant compound which can influence cartilage metabolism through multiple signalling pathways. This systematic review and meta-analysis aimed to summarize the therapeutic effects of resveratrol in animal models of OA. Methods: A comprehensive literature search was performed using PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Wanfang and VIP databases in May 2023. Studies on the effects of resveratrol in animal models of OA written in English or Mandarin, published from the inception of databases until the date of the search were considered. Results: Fifteen eligibility studies were included and analysed. Resveratrol was shown to inhibit the secretion of interleukin-1ß, tumour necrosis factor-α, interleukin-6, nitric oxide, and apoptosis of articular chondrocytes. Joint structure as indicated by Mankin scores was restored with resveratrol in animal OA models. Conclusion: Resveratrol is a potential therapeutic agent for OA based on animal studies. Further evidence from well-planned human studies would be required to validate its clinical efficacies.

Updates in the skeletal and joint protective effects of tocotrienol: a mini review.

Osteoporosis and osteoarthritis continue to pose significant challenges to the aging population, with limited preventive options and pharmacological treatments often accompanied by side effects. Amidst ongoing efforts to discover new therapeutic agents, tocotrienols (TTs) have emerged as potential candidates. Derived from annatto bean and palm oil, TTs have demonstrated efficacy in improving skeletal and joint health in numerous animal models of bone loss and osteoarthritis. Mechanistic studies suggest that TTs exert their effects through antioxidant, anti-inflammatory, Wnt-suppressive, and mevalonate-modulating mechanisms in bone, as well as through self-repair mechanisms in chondrocytes. However, human clinical trials in this field remain scarce. In conclusion, TTs hold promise as agents for preventing osteoporosis and osteoarthritis, pending further evidence from human clinical trials.

Roles of long non­coding RNAs in esophageal cell squamous carcinoma (Review).

Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly malignancy of the digestive tract. Recent research has identified long non­coding RNAs (lncRNAs) as crucial regulators in the pathogenesis of ESCC. These lncRNAs, typically exceeding 200 nucleotides, modulate gene expression through various mechanisms, including the competing endogenous RNA (ceRNA) pathway and RNA­protein interactions. The current study reviews the multifaceted roles of lncRNAs in ESCC, highlighting their involvement in processes such as proliferation, migration, invasion, epithelial­mesenchymal transition, cell cycle progression, resistance to radiotherapy and chemotherapy, glycolysis, apoptosis, angiogenesis, autophagy, tumor growth, metastasis and the maintenance of cancer stem cells. Specific lncRNAs like HLA complex P5, LINC00963 and non­coding repressor of NFAT have been shown to enhance resistance to radio­ and chemotherapy by modulating pathways such as AKT signaling and microRNA interaction, which promote cell survival and proliferation under therapeutic stress. Furthermore, lncRNAs like family with sequence similarity 83, member A antisense RNA 1, zinc finger NFX1­type containing 1 antisense RNA 1 and taurine upregulated gene 1 are implicated in enhancing invasive and proliferative capabilities of ESCC cells through the ceRNA mechanism, while interactions with RNA­binding proteins further influence cancer cell behavior. The comprehensive analysis underscores the potential of lncRNAs as biomarkers for prognosis and therapeutic targets in ESCC, suggesting avenues for future research focused on elucidating the detailed molecular mechanisms and clinical applications of lncRNAs in ESCC management.

Single high-dose intravenous injection of Wharton's jelly-derived mesenchymal stem cell exerts protective effects in a rat model of metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility. This study aims to investigate WJ-MSCs as a therapy against MetS in a rat model. METHODS: Twenty-four animals were fed with high-fat high-fructose (HFHF) diet ad libitum. After 16 weeks, the animals were randomised into treatment groups (n = 8/group) and received a single intravenous administration of vehicle, that is, 3 × 106 cells/kg or 10 × 106 cells/kg of WJ-MSCs. A healthy animal group (n = 6) fed with a normal diet received the same vehicle as the control (CTRL). All animals were periodically assessed (every 4 weeks) for physical measurements, serum biochemistry, glucose tolerance test, cardiovascular function test and whole-body composition. Post-euthanasia, organs were weighed and processed for histopathology. Serum was collected for C-reactive protein and inflammatory cytokine assay. RESULTS: The results between HFHF-treated groups and healthy or HFHF-CTRL did not achieve statistical significance (α = 0.05). The effects of WJ-MSCs were masked by the manifestation of different disease subclusters and continuous supplementation of HFHF diet. Based on secondary analysis, WJ-MSCs had major implications in improving cardiopulmonary morbidities. The lungs, liver and heart show significantly better histopathology in the WJ-MSC-treated groups than in the untreated CTRL group. The cells produced a dose-dependent effect (high dose lasted until week 8) in preventing further metabolic decay in MetS animals. CONCLUSIONS: The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.

Deleterious Biological Effects of Endocrine Disruptors: An Insight into Human Health Risks.

Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.

Effects of Tenofovir Disoproxil Fumarate on Bone Quality beyond Bone Density-A Scoping Review of the Literature.

Tenofovir disoproxil fumarate (TDF) is a widely used pharmacological agent for the treatment of human immunodeficiency virus infection. While prolonged exposure to TDF has been associated with a decrease in bone mineral density (BMD) and increased fracture risk, limited discussion exists on its effects on various aspects of bone quality. This scoping review aims to provide a comprehensive overview of the impact of TDF on bone quality beyond BMD. A literature search was conducted using the PubMed and Scopus databases to identify studies investigating the effects of TDF on bone quality. Original research articles written in English, irrespective of study type or publication year, were included in the review. Seven articles met the inclusion criteria. Findings indicate that prolonged exposure to TDF adversely affects bone microarchitecture and strength, impeding fracture healing and skeletal microdamage repair. The observed effects suggest a complex interplay involving bone cell signalling, cytokines and bone remodelling processes as potential mechanisms underlying TDF's impact on bone quality. As a conclusion, TDF impairs bone remodelling and microarchitecture by influencing dynamic bone cell behaviour and signalling pathways. Future studies should delve deeper into understanding the intricate negative effects of TDF on bone and explore strategies for reversing these effects.

Effects of emulsified and non-emulsified palm tocotrienol on bone and joint health in ovariectomised rats with monosodium iodoacetate-induced osteoarthritis.

Postmenopausal women are susceptible to osteoporosis and osteoarthritis. Tocotrienol, a bone-protective nutraceutical, is reported to prevent osteoarthritis in male rats. However, its efficacy on joint health in oestrogen deficiency has not been validated. Besides, data on the use of emulsification systems in enhancing bioavailability and protective effects of tocotrienol are limited. Ovariectomised adult female Sprague-Dawley rats (3 months old) were treated with refined olive oil, emulsified (EPT, 100 mg/kg/day with 25% vitamin E content), non-emulsified palm tocotrienol (NEPT, 100 mg/kg/day with 50% vitamin E content) and calcium carbonate (1% w/v in drinking water) plus glucosamine sulphate (250 mg/kg/day) for 10 weeks. Osteoarthritis was induced with monosodium iodoacetate four weeks after ovariectomy. Baseline control was sacrificed upon receipt, while the sham group was not ovariectomised and treated with refined olive oil. EPT and NEPT prevented femoral metaphyseal and subchondral bone volume decline caused by ovariectomy. EPT decreased subchondral trabecular separation compared to the negative control. EPT preserved stiffness and Young's Modulus at the femoral mid-shaft of the rats. Circulating RANKL was reduced post-treatment in the EPT group. Joint width was reduced in all the treatment groups vs the negative control. The EPT group's grip strength was significantly improved over the negative control and NEPT group. EPT also preserved cartilage histology based on several Mankin's subscores. EPT performed as effectively as NEPT in preventing osteoporosis and osteoarthritis in ovariectomised rats despite containing less vitamin E content. This study justifies clinical trials for the use of EPT in postmenopausal women with both conditions.

Potential role of geranylgeraniol in managing statin-associated muscle symptoms: a COVID-19 related perspective.

Myopathy is the most common side effect of statins, but it has not been addressed effectively. In anticipation of its wider use as a small molecule to complement the current COVID-19 management, a pharmacological solution to statin-associated muscle symptoms (SAMS) is warranted. Statins act by suppressing the mevalonate pathway, which in turn affects the downstream synthesis of isoprenoids required for normal physiological functions. CoQ10 and geranylgeraniol (GG) syntheses are reduced by statin use. However, CoQ10 supplementation has not been shown to reverse SAMS. GG is an obligatory substrate for CoQ10 synthesis, an endogenous nutrient critical for skeletal muscle protein synthesis. Multiple studies showed GG supplementation is effective in reversing SAMS. This opinion paper proposes employing GG to prevent SAMS in pleiotropic statin use, including usage in the post-COVID-19 pandemic era.

Serum Metabolomic Alteration in Rats with Osteoarthritis Treated with Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate.

Osteoarthritis (OA) is a degenerative joint condition with limited disease-modifying treatments currently. Palm tocotrienol-rich fraction (TRF) has been previously shown to be effective against OA, but its mechanism of action remains elusive. This study aims to compare serum metabolomic alteration in Sprague-Dawley rats with monosodium iodoacetate (MIA)-induced OA which were treated with palm TRF, glucosamine sulphate, or a combination of both. This study was performed on thirty adult male rats, which were divided into normal control (n = 6) and OA groups (n = 24). The OA group received intra-articular injections of MIA and daily oral treatments of refined olive oil (vehicle, n = 6), palm TRF (100 mg/kg, n = 6), glucosamine sulphate (250 mg/kg, n = 6), or a combination of TRF and glucosamine (n = 6) for four weeks. Serum was collected at the study's conclusion for metabolomic analysis. The findings revealed that MIA-induced OA influences amino acid metabolism, leading to changes in metabolites associated with the biosynthesis of phenylalanine, tyrosine and tryptophan as well as alterations in the metabolism of phenylalanine, tryptophan, arginine and proline. Supplementation with glucosamine sulphate, TRF, or both effectively reversed these metabolic changes induced by OA. The amelioration of metabolic effects induced by OA is linked to the therapeutic effects of TRF and glucosamine. However, it remains unclear whether these effects are direct or indirect in nature.

Preventative and therapeutic potential of tocotrienols on musculoskeletal diseases in ageing.

Musculoskeletal health is paramount in an ageing population susceptible to conditions such as osteoporosis, arthritis and fractures. Age-related changes in bone, muscle, and joint function result in declining musculoskeletal health, reduced mobility, increased risk of falls, and persistent discomfort. Preserving musculoskeletal wellbeing is essential for maintaining independence and enhancing the overall quality of life for the elderly. The global burden of musculoskeletal disorders is significant, impacting 1.71 billion individuals worldwide, with age-related muscle atrophy being a well-established phenomenon. Tocotrienols, a unique type of vitamin E found in various sources, demonstrate exceptional antioxidant capabilities compared to tocopherols. This characteristic positions them as promising candidates for addressing musculoskeletal challenges, particularly in mitigating inflammation and oxidative stress underlying musculoskeletal disorders. This review paper comprehensively examines existing research into the preventive and therapeutic potential of tocotrienols in addressing age-related musculoskeletal issues. It sheds light on the promising role of tocotrienols in enhancing musculoskeletal health and overall wellbeing, emphasizing their significance within the broader context of age-related health concerns.

The effects of E'Jiao on body composition, bone marrow adiposity and skeletal redox status in ovariectomised rats.

Background: Menopause is accompanied by increased oxidative stress, partly contributing to weight gain and bone marrow adiposity. Traditional Chinese medication, E'Jiao, has been demonstrated to reduce excessive bone remodelling during oestrogen deprivation, but its effects on body composition and bone marrow adiposity during menopause remain elusive. Objective: To determine the effects of E'Jiao on body composition, bone marrow adiposity and skeletal redox status in ovariectomised (OVX) rats. Methods: Seven groups of three-month-old female Sprague Dawley rats were established (n=6/group): baseline, sham, OVX control, OVX-treated with low, medium or high-dose E'Jiao (0.26, 0.53, 1.06 g/kg, p.o.) or calcium carbonate (1% in tap water, ad libitum). The supplementation was terminated after 8 weeks. Whole-body composition analysis was performed monthly using dual-energy X-ray absorptiometry. Analysis of bone-marrow adipocyte numbers and skeletal antioxidant activities were performed on the femur. Results: Increased total mass, lean mass, and bone marrow adipocyte number were observed in the OVX control versus the sham group. Low-dose E'Jiao supplementation counteracted these changes. Besides, E'Jiao at all doses increased skeletal catalase and superoxide dismutase activities but lowered glutathione levels in the OVX rats. Skeletal malondialdehyde level was not affected by ovariectomy but was lowered with E'Jiao supplementation. However, peroxisome proliferator-activated receptor gamma protein expression was not affected by ovariectomy or any treatment. Conclusion: E'Jiao, especially at the low dose, prevented body composition changes and bone marrow adiposity due to ovariectomy. These changes could be mediated by the antioxidant actions of E'Jiao. It has the potential to be used among postmenopausal women to avoid adiposity.

A Systematic Review on the Increasing Incidence of Inflammatory Bowel Disease in Southeast Asia: Looking Beyond the Urbanization Phenomenon.

The incidence of inflammatory bowel disease (IBD) has been increasing in Southeast Asia (SEA) in tandem with its economic growth and urbanization over the past 2 decades. Specific characteristics of IBD in SEA are similar to East Asia and the West, such as the declining ratio of ulcerative colitis to Crohn's disease. However, exceptionally low familial aggregation is seen. Smoking is also not a common risk factor in patients with Crohn's disease. The incidence of perianal disease is higher in SEA than in Australia and is comparable to the West. In a multiracial population, such as Singapore and Malaysia, Indians have the highest incidence and prevalence rates, which are likely to be due to important putative mutations. For instance, a higher frequency of the NOD2 predisposing mutation SNP5 and IBD risk allele IGR2198a and IGR2092a were found in Indians. Although differences in the genetic constitution play an important role in the epidemiology and prognosis of IBD in SEA, the emergence of this disease offers a unique opportunity to identify potential exposomes that contribute to its pathogenesis.

Therapeutic potential of bixin on inflammation: a mini review.

Chronic inflammation is the underlying mechanism for many diseases. Thus, inflammatory signaling pathways are valuable targets for new treatment modalities. Natural products have gained interest as a potential source of bioactive compounds which provide health benefits in combating inflammatory-related diseases. Recent reports have linked the medicinal values of Bixa orellana L. with its anti-inflammatory activities. Therefore, this review aims to examine the therapeutic potential of bixin, a major bioactive constituent found in the seeds of B. orellana, on inflammatory-related diseases based on existing in vitro and in vivo evidence. Additionally, the anti-inflammatory mechanism of bixin via signaling pathways is explored and possible toxic effects are addressed. The findings suggest that bixin may ameliorate inflammation via inhibition of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and thioredoxin-interacting protein/NOD-like receptor protein 3 (TXNIP/NLRP3) inflammasome mechanisms. More well-planned clinical studies should be performed to verify its effectiveness and safety profile.

The Effects of Tocotrienol on Gut Microbiota: A Scoping Review.

Gut dysbiosis has been associated with many chronic diseases, such as obesity, inflammatory bowel disease, and cancer. Gut dysbiosis triggers these diseases through the activation of the immune system by the endotoxins produced by gut microbiota, which leads to systemic inflammation. In addition to pre-/pro-/postbiotics, many natural products can restore healthy gut microbiota composition. Tocotrienol, which is a subfamily of vitamin E, has been demonstrated to have such effects. This scoping review presents an overview of the effects of tocotrienol on gut microbiota according to the existing scientific literature. A literature search to identify relevant studies was conducted using PubMed, Scopus, and Web of Science. Only original research articles which aligned with the review's objective were examined. Six relevant studies investigating the effects of tocotrienol on gut microbiota were included. All of the studies used animal models to demonstrate that tocotrienol altered the gut microbiota composition, but none demonstrated the mechanism by which this occurred. The studies induced diseases known to be associated with gut dysbiosis in rats. Tocotrienol partially restored the gut microbiota compositions of the diseased rats so that they resembled those of the healthy rats. Tocotrienol also demonstrated strong anti-inflammatory effects in these animals. In conclusion, tocotrienol could exert anti-inflammatory effects by suppressing inflammation directly or partially by altering the gut microbiota composition, thus achieving its therapeutic effects.

Vitamin E in the management of pancreatic cancer: A scoping review.

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.

Metabolic Syndrome Screening and Nutritional Status of Patients with Psoriasis: A Scoping Review.

Background: Patients with plaque psoriasis have an increased risk of metabolic syndrome. However, no studies have assessed the nutritional status or screening methods of this population. Aims: This review aimed to identify and summarise metabolic syndrome screening criteria and the tools/methods used in nutrition assessment in patients with plaque psoriasis. Data synthesis: PubMed, Web of Science, Ovid and Scopus were searched from inception to March 2023, following the Arkensey and O'Malley framework, to identify articles that report nutritional assessment methods/tools and metabolic screening criteria. Twenty-one studies were identified. Overall, these studies used four different screening criteria to define metabolic syndrome. Patients with psoriasis had a high prevalence of metabolic syndrome and had a poor nutritional status compared to controls. However, only anthropometric measures such as weight, height and waist circumference were employed to determine the nutritional status. Only two studies assessed the vitamin D status. Conclusions: Patients with psoriasis have a poor nutritional status, and they are at risk of nutrient deficiencies. However, these health aspects are not routinely assessed and may increase the risk of malnutrition among these patients. Therefore, additional assessments, such as body composition and dietary assessment, are needed to determine the nutritional status to provide a suitable intervention.

Curcumin as a Therapeutic Agent for Sarcopenia.

Sarcopenia is the progressive loss of muscle mass, strength, and functions as we age. The pathogenesis of sarcopenia is underlined by oxidative stress and inflammation. As such, it is reasonable to suggest that a natural compound with both antioxidant and anti-inflammatory activities could prevent sarcopenia. Curcumin, a natural compound derived from turmeric with both properties, could benefit muscle health. This review aims to summarise the therapeutic effects of curcumin on cellular, animal, and human studies. The available evidence found in the literature showed that curcumin prevents muscle degeneration by upregulating the expression of genes related to protein synthesis and suppressing genes related to muscle degradation. It also protects muscle health by maintaining satellite cell number and function, protecting the mitochondrial function of muscle cells, and suppressing inflammation and oxidative stress. However, it is noted that most studies are preclinical. Evidence from randomised control trials in humans is lacking. In conclusion, curcumin has the potential to be utilised to manage muscle wasting and injury, pending more evidence from carefully planned human clinical trials.