将以下文字翻译为英文并润色。PBC 是一种慢性、胆汁淤积为特征的自身免疫性肝病 主要累及 40-60 岁女性表现为乏力、瘙痒、黄疸等其病程可持续数十年之久1 2。其发病原因尚不明确普遍被认为是遗传、炎症和环境因素共同作用所致。病理特征是门静脉区淋巴细胞浸润胆管上皮细胞被破坏并产生抗线粒体抗体 Anti-mitochondrialantibodyAMA导致肝内胆汁淤积并最终造成肝硬化3。AMA 在
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis, primarily affecting women aged 40-60 years, with symptoms such as fatigue, itching, and jaundice, and can last for decades. Its cause is not yet clear, but it is generally believed to be the result of a combination of genetic, inflammatory, and environmental factors. The pathological features include lymphocyte infiltration in the portal vein area, destruction of bile duct epithelial cells, and the production of anti-mitochondrial antibodies (AMA), leading to intrahepatic cholestasis and ultimately, liver cirrhosis. AMA is highly specific in PBC and is therefore the main antibody used for diagnosis, along with other specific antibodies such as anti-gp210 and anti-sp100. The worldwide prevalence of PBC is 20-40/100,000 people, and the number of cases is increasing each year, especially in asymptomatic individuals, mainly due to increased awareness of PBC and early detection of antibodies. In the early stages of PBC, there are usually no obvious symptoms, and only AMA positivity or elevated alkaline phosphatase (ALP) levels are present. As the disease progresses, patients gradually develop symptoms such as fatigue, itching, jaundice, and depression, and serum tests reveal elevated levels of gamma-glutamyl transferase (GGT) or ALP, as well as other biochemical abnormalities. Some young PBC patients have a rapid disease progression, leading to liver cirrhosis and liver transplantation. Ursodeoxycholic acid (UDCA) is currently the first-line drug for PBC, and obeticholic acid is the second-line drug, both of which can reduce intrahepatic cholestasis. NK cells, as a type of lymphocyte, play an important role in liver homeostasis and are believed to play an indispensable role in the progression of PBC due to their adaptive immune characteristics. Immunogenetic studies have shown that polymorphisms, including the NFAT and IL-12/stat4 pathways, are associated with PBC. In patients with PBC, the number of NK cells increases and accumulates around the affected small bile ducts, inducing apoptosis of biliary epithelial cells (BECs). NFATC1 is a gene that induces immune responses and regulates cells by binding to the CD16 molecule on the surface of NK cells. As early as 1995, Aramburu et al. demonstrated that the NFAT pathway plays an important role in PBC. A recent study showed that blocking the NFAT pathway has a relieving effect on intrahepatic cholestasis. The activation of T cell transcription factor c (NFATC) plays a decisive role in the development of the immune system and adaptive immune responses. In NK cells, lactic acid or hydrochloric acid inhibits the upregulation of NFAT activation, and data suggest that the inhibition of NFAT is the main reason for the inhibitory effect of NK cell activation. Therefore, the NFATC1 gene, which regulates the NFAT pathway, is necessary for the study of NK cell regulation. miRNA is a short chain RNA produced by mRNA degradation, widely present in the body, which can bind or degrade target mRNA to inhibit gene expression, and regulate the metabolism and protein expression of the internal environment. Many different types of miRNA are involved in different stages of chronic liver disease, including cholestasis and liver fibrosis. There are hundreds of differentially expressed miRNAs in the serum and PBMCs of PBC patients. More and more studies have reported the miRNA spectrum of PBC patients and their potential value in diagnosis and evaluation of treatment efficacy. Compared with healthy controls (HCs), the levels of miR-21 and miR-210 in liver tissue of PBC patients were elevated, and 35 miRNAs were found to be differentially expressed in end-stage PBC patients compared with HCs. In another validation experiment, it was confirmed that the upregulation of miR-122a and miR-26a, and the downregulation of miR-328 and miR-299-5p in the liver tissue of PBC patients were closely related to the pathogenesis of PBC, including biliary inflammation, cell apoptosis, and reactive oxygen species. Although the role of miRNA in PBC has been revealed, there is no study on the role of miRNA in lymphocytes in PBC. More than 400 and 300 miRNAs have been found in human and mouse NK cells, respectively, some of which play an important role in the development and maturation of NK cells. KIR, KLR, and NKG2D are common genes related to NK cell activation, but no miRNA with a strong correlation has been found in the gene prediction process. Therefore, this study introduces the NFATC1 gene and aims to explore the role of miRNA in NK cell activation in PBC and to find miRNAs that can regulate PBC, thus expanding the pathogenesis of PBC and providing valuable information for future diagnosis and treatment diversity
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