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:Heterogeneous population of macrophages in the development of non-alcoholic fatty liver disease.
Heterogeneous population of macrophages in the development of non-alcoholic fatty liver disease.
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非酒精性脂肪性肝病(NAFLD)以一系列肝脏疾病为特征,包括脂肪肝、非酒精性脂肪性肝炎、肝硬化和肝细胞癌。NAFLD是代谢综合征的肝脏表现,已成为肝移植的主要原因,因此需要深入理解其潜在致病机制并确定可行的药物靶点。尽管脂肪肝是良性的,不会造成明显的肝损伤或炎症,但NAFLD的进展涉及由免疫细胞促进的炎症过程。巨噬细胞和单核细胞构成了固有免疫细胞池,与其他细胞类型(如中性粒细胞、T细胞和NK 细胞)协同促进NAFLD的发展。巨噬细胞在NAFLD发展过程中促进炎症过程的这一概念长期以来一直存在争议;然而,实验技术的显著进步迅速揭示了巨噬细胞和单核细胞的新亚群,其功能需要全面阐明。本综述聚焦于近年来我们对在NAFLD发展中起关键作用的巨噬细胞异质性群体认知的扩展。此外,本文还讨论了目前为开发针对非酒精性脂肪性肝炎的最佳治疗药物而靶向巨噬细胞和炎症过程的努力。
Non-alcoholic fatty liver disease (NAFLD) is characterized by a spectrum of hepatic diseases, including fatty liver, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. NAFLD is a hepatic manifestation of metabolic syndrome and has become the leading cause of liver transplantation, necessitating an in-depth understanding of its underlying pathogenic mechanisms and the identification of viable drug targets. Although fatty liver is benign and does not exert marked liver damage or inflammation, NAFLD progression involves inflammatory processes facilitated by immune cells.
Macrophages and monocytes constitute the pool of innate immune cells that contribute to NAFLD development in association with other cell types, such as neutrophils, T cells, and natural killer cells.
The concept that macrophages contribute to the inflammatory processes in NAFLD development has long been debated; however, the remarkable advances in experimental techniques have rapidly uncovered new subpopulations of macrophages and monocytes, whose functions need to be comprehensively elucidated. The current review focuses on the recent expansion of our knowledge of the heterogeneous population of macrophages crucially involved in NAFLD development.
In addition, the present paper discusses ongoing efforts to target macrophages and inflammatory processes to develop optimal therapeutic agents against non-alcoholic steatohepatitis.
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