RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Innate Immunity and MASLD.
Innate Immunity and MASLD.
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代谢功能障碍相关脂肪性肝病(MASLD)近年来已成为全球最常见的肝脏疾病。MASLD通常表现为单纯性肝脂肪变性,但约25%的患者会发展为肝脏炎症、进行性纤维化、肝硬化及相关肝细胞癌。肝脏炎症和纤维化程度是预后的关键决定因素。肝脏炎症的病理生理机制尚未完全阐明,涉及多种因素,特别是固有免疫和适应性免疫应答。更具体地说,固有免疫的多种介质,如促炎细胞因子、脂肪因子、炎症小体以及单核细胞、巨噬细胞和NK 细胞等多种细胞类型,均参与引导MASLD中的炎症过程。固有免疫的激活由多种因素驱动,包括过量脂质和脂毒性、胰岛素抵抗以及来源于肠道共生菌的分子模式。因此,靶向固有免疫通路可能成为未来MASLD及其并发症管理中一种有吸引力的治疗策略。
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses.
More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD.
The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications.
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