Vitamin B12 Metabolism

This is an open access article under the CC BYNCND license. Collectively, dysfunctional gene products may disrupt immune homeostasis by regulating cytokine production, immune tolerance and immune responses.Nevertheless, the precise mechanisms of AILD development remain obscure.For example, elevated serum miR and miR levels show diagnostic utility in AIH. Moreover, transfection of dierent miRNA mimics or antagonists, such as atagomiR and miR mimics, has been widely performed in experimental AILD mouse models with great ecacy. The binding site in a target RNA is located in the untranslated region, which is recognized by the seed sequence of the miRNA through base pairing.Ultimately, miRISC:mRNA interactions contribute to deadenylation, degradation, or translational suppression of the mRNA, thus inhibiting target gene expression. Despite a broad understanding of imbalanced hepatic immune homeostasis driven by environmental, genetic, and epigenetic factors, the underlying molecular mechanisms of AIH remain elusive.The age of AIH onset has a bimodal pattern, whereby teenagers and older people from to years old are predominantly aected. In general, prednisolone plus azathioprine is recommended as the rstline therapy to induce biochemical remission. Although of AIH patients show a complete response to standard therapy with glucocorticoids and immunosuppressants, some cases may rapidly progress to hepatic cirrhosis or liver failure due to severe side eects, poor response during the remission period, and high relapse rate after drug withdrawal. Hence, it is necessary to research the pathogenesis of AIH and explore novel and eective therapies.Macrophages play a pivotal role in maintaining hepatic immune homeostasis. MiR deciency also leads to impaired recruitment of regulatory T cells. Restoration of miR in knockout mice by bone marrow transplantation markedly reduces hepatic necrosis and inammation, revealing a protective role for miR in AIH.Nonetheless, another study has shown the opposite eect of miR on AIH.MiRNA has been implicated in several diseases related to brosis.The diagnosis of PBC is based on elevated alkaline phosphatase, and characteristic orid duct lesions. Ursodeoxycholic acid is commonly considered an eective tool for ameliorating bile duct inammation and improving survival, but a proportion of PBC patients has an incomplete response.In addition, utilization of obeticholic acid in several randomized clinical trials has shown striking improvements in biochemical abnormalities, histological features, and poor prognoses. As T cellmediated inammatory responses and an impaired bicarbonate umbrella have been demonstrated in PBC, further explorations of the molecular mechanisms are necessary to facilitate novel curative options.MiR and miR levels in liver tissues of PBC patients are increased compared to those of healthy subjects. In addition, a cohort study including PBC patients with UDCA or bezabrate treatment has been performed to compare the refractory group with the nonrefractory group. Circulating exosomes, nanoparticles with nucleic acid and protein cargo, have been reported to participate in the development of various autoimmune diseases. Nevertheless, miR is probably the only miRNA with a functional role in the immunopathogenesis of PBC.MiR upregulation has been conrmed in liver biopsies from an independent cohort of PBC patients compared to healthy controls and PSC patients. Moreover, in vitro data indicated that miR reduces expression of AE by binding to the UTR region of the target mRNA, leading to impaired AE activity in biliary epithelium cells but that transfection of antimiR oligonucleotides restores the diminished AE activity.

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