Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis
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Rheumatoid arthritis (RA) as a complex disease is thought triggered by interaction between genetics and environment, especially the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, all the evidence shows genetic diversity and environment exposure cannot explain all the clinical characteristics heterogeneity of rheumatoid arthritis. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of rheumatoid arthritis, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adoptive immune cell differentiation and the migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic mediated regulation to immune genes and inflammation pathway provides well explanation to dynamic expression network of rheumatoid arthritis. In this review, we summarized the comprehensive evidence to show methylation modification occurred in DNA and histone are significantly involved in the pathogenesis of rheumatoid arthritis and could be applied as the promising biomarker in the disease activity and drug response prediction. We also explained the opportunity and challenge of the current epigenetics research in rheumatoid arthritis. In summary, epigenetic modules provide possible interface through which genetic and environmental risk factors connect together to contribute to the susceptibility and pathogenesis of RA. Meanwhile epigenetic regulators provided promising drug targets to develop novel therapeutic drugs for rheumatoid arthritis. Finally, DNA methylation and histone modification will be important features to provide better rheumatoid arthritis subtype identification to accelerate personalized treatment and precision medicine.Keywords:
Pathogenesis
DNA demethylation
Epigenomics
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Radiosynoviorthese, a new method for the treatment of patients with rheumatoid arthritis, was developed. Altogether 260 patients with rheumatoid arthritis were treated. The therapeutic activity of radioactive colloid Au was administered intra-articularly to all the patients. Indications and contraindications for radiation therapy of rheumatoid arthritis were developed. Good short- and long-term results were noted in most of the patients after radiation therapy. Radiosynoviorthese as a method of local active therapy of affected joints with colloid Au in the multiple modality treatment of rheumatoid arthritis is effective; its prolonged stable therapeutic effect in patients is observed.
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Epigenetic alterations during aging are manifested with altered gene expression linking it to lifespan regulation, genetic instability, and diseases. Diet and epigenetic modifiers exert a profound effect on the lifespan of an organism by modulating the epigenetic marks. However, our understanding of the multifactorial nature of the epigenetic process during aging and the onset of disease conditions as well as its reversal by epidrugs, diet, or environmental factors is still mystifying. This review covers the key findings in epigenetics related to aging and age-related diseases. Furthermore, it holds a discussion about the epigenetic clocks and their implications in various age-related disease conditions, including cancer. Although, epigenetics is a reversible process, how fast the epigenetic alterations can revert to normal is an intriguing question. Therefore, this article touches on the possibility of utilizing nutrition and mesenchymal stem cell secretome to accelerate the epigenetic reversal and emphasizes the identification of new therapeutic epigenetic modifiers to counter epigenetic alteration during aging.
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Epigenetics describes the study of cellular modifications that can modify the expression of genes without changing the DNA sequence. DNA methylation is one of the most stable and prevalent epigenetic mechanisms. Twin studies have been a valuable model for unraveling the genetic and epigenetic epidemiology of complex traits, and now offer a potential to dissect the factors that impact DNA methylation variability and its biomedical significance. The twin design specifically allows for the study of genetic, environmental and lifestyle factors, and their potential interactions, on epigenetic profiles. Furthermore, genetically identical twins offer a unique opportunity to assess nongenetic impacts on epigenetic profiles. Here, we summarize recent findings from twin studies of DNA methylation profiles across tissues, to define current knowledge regarding the genetic and nongenetic factors that influence epigenetic variation.
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TOBACCO AND DNA METHYLATION THE CASE FOR EPIGENETIC ALTERATIONS The mechanisms of the long-term impacts of exposure to chemical substances remain poorly understood. While genotoxic and mutagenic effects have been well characterized, epigenetic mechanisms such as DNA methylation could also account for the delayed effects of exposures. It is in the case of tobacco that the strongest arguments for a role of these mechanisms have been obtained in human populations. This text presents recent data on this issue demonstrating the plausibility of epigenetic mechanisms to explain the persistence of biological signals long after stopping exposure.
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Rheumatoid Arthritis is found to be very effective in alleviating the symptoms in the hapless victims of rheumatoid arthritis as stipulated in ashtanga hridaya. This paper deals with the role of asteracantha longifolia in the treatment of Rheumatoid arthritis. But in the initial stages the paneeya made out of kokilasha (Asteracantha longifolia) is found to be very effective in alleviating the symptoms in the hapless victims of rheumatoid arthritis as stipulated in ashtanga hridaya. This paper deals with the role of asteracantha longifolia in the treatment of Rheumatoid arthritis.
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Transient nutritional exposures during critical ontogenic periods can cause persistent changes in gene expression, metabolism, and risk of various diseases. We have been investigating whether such ‘developmental programming’ occurs via nutritional influences on developmental epigenetics. Our studies in agouti viable yellow and axin-fused mice showed that developmental establishment of DNA methylation at ‘metastable epialleles’ is especially sensitive to maternal nutritional status around the time of conception. At metastable epialleles, DNA methylation is established stochastically in the early embryo and subsequently maintained during differentiation of diverse lineages, resulting in systemic interindividual epigenetic variation that is not genetically mediated. Lately, using a multiple-tissue screen for interindividual variation in DNA methylation, we have identified human genomic regions that appear to be metastable epialleles. Stochastic establishment of DNA methylation at these loci is affected by maternal nutrition around the time of conception, consistent across multiple tissues, and stable for many years. Most recently, our studies using genome-wide bisulfite sequencing have identified candidate metastable epialleles that are associated with human disease, providing exciting opportunities for epigenetic epidemiology.
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AbstractIn this study, we aimed to investigate the levels of serum Zn, Cu, Mg, Mn, and Fe in rheumatoid arthritis and whether they are related to the severity of the disease. The sera from 29 patients with rheumatoid arthritis were studied and compared with those from healthy controls (n = 22). Although serum Fe, Mg and Mn levels were lower in the rheumatoid arthritis group than in the control group, the difference was not statistically significant. Significantly higher Cu (p < 0.001) and lower Zn serum levels (p < 0.012) were found in rheumatoid arthritis than in controls.A statistically significant positive correlation was present between Cu levels and disease activity score (DAS), and there was a negative correlation between Zn levels and DAS.We think that alterations of the level of some trace elements in rheumatoid arthritis are a consequence of and not one of the causes of the disease, as in many other chronic inflammatory disorders.Keywords: Rheumatoid arthritiszinccoppermagnesiummanganeseiron.
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Inheritance
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