Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China.
Department of Children Health Care, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430061, Hubei Province, China.
World J Gastroenterol. 2024 Sep 7;30(33):3791-3798. doi: 10.3748/wjg.v30.i33.3791.
In this editorial, we comment on the article published in the recent issue of the . Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.
在这篇社论中，我们对近期发表在 上的一篇文章进行了评论。急性肝衰竭（ALF）是一种致命疾病，可导致大量肝细胞不受控制地死亡和肝功能迅速丧失。铁死亡和细胞焦亡是可以同时启动或阻断的细胞死亡形式，它们在炎症和各种恶性肿瘤的发生中发挥着重要作用。然而，它们在 ALF 中的作用尚不清楚。该文章发现了铁死亡和细胞焦亡在 ALF 进展过程中的正反馈，揭示了沉默信息调节因子 SIRT1 通过 p53 抑制这两条途径，显著减少炎症并保护肝细胞。这表明 SIRT1 及其下游分子可能作为 ALF 的治疗靶点。因此，我们将讨论铁死亡和细胞焦亡在 ALF 中的作用以及这两种细胞死亡机制之间的相互作用。此外，我们还探讨了通过同时抑制这两条细胞死亡途径来缓解 ALF 的潜在治疗方法，以及 SIRT1 激活剂作为疾病治疗策略的应用实例，为 ALF 的治疗提供了新的思路。
