Regulated necrosis pathways: a potential target for ischemic stroke.

Globally, ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region. In the infarct region, cell injuries follow either the regulated pathway involving precise signaling cascades, such as apoptosis and autophagy, or the nonregulated pathway, which is uncontrolled by any molecularly defined effector mechanisms such as necrosis. However, numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic; this type of necrosis is referred to as regulated necrosis. Depending on the signaling pathway, various elements of regulated necrosis contribute to the development of ischemic stroke, such as necroptosis, pyroptosis, ferroptosis, pathanatos, mitochondrial permeability transition pore-mediated necrosis and oncosis. In this review, we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis. We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemia-induced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.

Research progress on the role of programmed cell death in hepatic ischemia-reperfusion injury / 器官移植

Liver transplantation is an effective treatment for the end-stage liver disease. However, hepatic ischemia-reperfusion injury (HIRI) will inevitably occur during liver transplantation, which might lead to early graft dysfunction or aggravate rejection. The underlying protective mechanism remains to be further elucidated. Programmed cell death is an important mechanism of HIRI, and multiple novel types of programmed cell death participate in the pathological process of HIRI. In-depth study of programmed cell death is expected to further improve the therapeutic effect of liver transplantation. In this article, research progresses on apoptosis, autophagy and autophagy-dependent cell death, ferroptosis, necroptosis, pyroptosis, pathanatos and other common programmed cell death patterns in HIRI were reviewed, aiming to provide reference for enhancing the success rate of liver transplantation and improving clinical prognosis of the recipients.