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Solid-State NMR Scientific studies from the Succinate-Acetate Permease through Citrobacter Koseri in Liposomes along with Indigenous Nanodiscs.
Multiple sclerosis (MS) is an aggravating autoimmune disease that cripples young patients slowly with physical, sensory and cognitive deficits. The break of self-tolerance to neuronal antigens is the key to the pathogenesis of MS, with autoreactive T cells causing demyelination that subsequently leads to inflammation-mediated neurodegenerative events in the central nervous system. The exact etiology of MS remains elusive; however, the interplay of genetic and environmental factors contributes to disease development and progression. Given that genetic variation only accounts for a fraction of risk for MS, extrinsic risk factors including smoking, infection and lack of vitamin D or sunshine, which cause changes in gene expression, contribute to disease development through epigenetic regulation. To date, there is a growing body of scientific evidence to support the important roles of epigenetic processes in MS. In this chapter, the three main layers of epigenetic regulatory mechanisms, namely DNA methylation, histone modification and microRNA-mediated gene regulation, will be discussed, with a particular focus on the role of epigenetics on dysregulated immune responses and neurodegenerative events in MS. Also, the potential for epigenetic modifiers as biomarkers and therapeutics for MS will be reviewed.Primary Sjögren's syndrome (SjS) is a chronic and systemic autoimmune epithelitis with predominant female incidence, which is characterized by exocrine gland dysfunction. Incompletely understood, the etiology of SjS is multi-factorial and evidence is growing to consider that epigenetic factors are playing a crucial role in its development. Independent from DNA sequence mutations, epigenetics is described as inheritable and reversible processes that modify gene expression. Epigenetic modifications reported in minor salivary gland and lymphocytes from SjS patients are related to (i) an abnormal DNA methylation process inducing in turn defective control of normally repressed genes involving such matters as autoantigens, retrotransposons, and the X chromosome in women; (ii) altered nucleosome positioning associated with autoantibody production; and (iii) altered control of microRNA. Results from epigenome-wide association studies have further revealed the importance of the interferon pathway in disease progression, the calcium signaling pathway for controlling fluid secretions, and a cell-specific cross talk with risk factors associated with SjS. Importantly, epigenetic modifications are reversible thus opening opportunities for therapeutic procedures in this currently incurable disease.Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with non-suppurative destruction of the intrahepatic bile ducts. The interplay of genetics and environmental triggers contributes to the onset of the disease and subsequently results in cholestasis and progressive fibrosis. Recently, genome-wide association studies (GWAS) have identified multiple genes influencing the susceptibility to PBC in HLA and non-HLA loci. However, it is estimated that the known risk variants merely account for no more than 20% of the heritability of PBC and causes of the remaining heritability remain uncertain. Increasing evidence suggests that the presence of epigenetic abnormalities may explain the "missing heritability" that cannot be captured by GWAS. Among these epigenetic mechanisms, DNA methylation, histone modification, and noncoding RNAs (i.e. miRNA and lncRNA) are involved in the pathogenesis of PBC. Additionally, telomere dysregulation in biliary epithelial cells (BECs) may play a role in disease onset, whereas a deficiency in sex chromosome and skewed gene expression in the X chromosome may to some extent explain the female dominance in PBC.Type 1 diabetes (T1D) is an autoimmune disease caused by the interaction between genetic alterations and environmental factors. More than 60 susceptible genes or loci of T1D have been identified. Among them, HLA regions are reported to contribute about 50% of genetic susceptibility in Caucasians. There are many environmental factors involved in the pathogenesis of T1D. Environmental factors may change the expression of genes through epigenetic mechanisms, thus inducing individuals with susceptible genes to develop T1D; however, the underlying mechanisms remain poorly understood. The major epigenetic modifications include DNA methylation, histone modification, and non-coding RNA. There has been extensive research on the role of epigenetic mechanisms including aberrant DNA methylation, histone modification, and microRNA in the pathogenesis of T1D. DNA methylation and microRNA have been proposed as biomarkers to predict islet β cell death, which needs further confirmation before any clinical application can be developed. Small molecule inhibitors of histone deacetylases, histone methylation, and DNA methylation are potentially important for preventing T1D or in the reprogramming of insulin-producing cells. This chapter mainly focuses on T1D-related DNA methylation, histone modification, and non-coding RNA, as well as their possible translational potential in the early diagnosis and treatment of T1D.Psoriasis is a chronic and recurrent inflammatory skin disease, involving the rapid proliferation and abnormal differentiation of keratinocytes and activation of T cells. It is generally accepted that the central pathogenesis of psoriasis is a T cell-dominant immune disorder affected by multiple factors including genetic susceptibility, environmental factors, innate and adaptive immune responses, etc. However, the exact etiology is largely unknown. In recent years, epigenetic involvements, such as the DNA methylation, chromatin modifications, and noncoding RNA regulation are reported to be critical for the pathogenesis of psoriasis. However, the interplay between these factors has only recently been started to be unraveled. Notably, inhibitors of enzymes that work in epigenetic modifications, such as DNA methyltransferases and histone deacetylases, are beginning to appear in the clinical setting to restore normal epigenetic patterns (Generali et al. Isuzinaxib mw in J Autoimmun 8351-61, 2017), providing novel therapeutic potential as novel treatment targets for psoriasis.
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