New insights into pharmacologic inhibition of pyroptotic cell death by necrosulfonamide: A PDE model
New insights into pharmacologic inhibition of pyroptotic cell death by necrosulfonamide: A PDE model
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死磺酰胺药理学抑制焦亡细胞死亡的新见解：PDE 模型
DOI：
10.1016/j.nonrwa.2020.103173
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Xiulan Lai
中科院分区：
文献类型：
--
作者：
Wei Wang;Xinzhi Ren;Wanbiao Ma;Xiulan Lai
细胞凋亡是一种高度炎症性的细胞死亡形式，其使用细胞内产生的孔来破坏电解质稳态并执行细胞死亡。Gasdermin D是细胞凋亡的成孔效应蛋白，在协调膜溶解和高度炎症分子的释放中起着关键作用。最近，necrosulfonamide作为gasdermin D的直接化学抑制剂已被证实结合gasdermin D以抑制pyroptotic细胞死亡。为了给gasdermin D抑制剂对细胞凋亡的影响提供更有效的理论指导，我们从遗传水平推导了一个新的PDE模型，并研究了其基于基本再生数R0的阈值动力学。结果表明，阈值动态由R0 − 1的符号决定。在适当的参数下，我们的数值模拟表明，在时间周期环境中，环境异质性可能会增加传输风险R0。如果使用时间平均系统，我们可能会低估R0。基于一些已发表的实验数据，给予坏死磺胺可能迅速增强患者的健康状况，这可能成为维持CD4+ T细胞计数在安全水平的新策略。
Pyroptosis is a highly inflammatory form of cell death, which uses intracellularly generated pores to destroy electrolyte homeostasis and perform cell death..Gasdermin D, the pore-forming effector protein of pyroptosis, plays a critical role in coordinating membrane lysis and the release of highly inflammatory.molecules. Recently, necrosulfonamide as a direct chemical inhibitor of gasdermin D has been confirmed to bind gasdermin D to inhibit pyroptotic cell death. To provide a more effective theoretical guidance for the influence of gasdermin D inhibitors on pyroptosis, we derive a novel PDE model from the genetic level, and study its threshold dynamics in terms of the basic reproduction number R0. It turns out that threshold dynamics is determined by the sign of R0 − 1. Under some suitable parameters, our numerical simulations show that environmental heterogeneity may increase transmission risk R0 in time periodic environments. We may underestimate R0 if the time average system is used. Based on some published experimental data, the administration of necrosulfonamide maybe strengthen the health condition of patients rapidly, which may become a new strategy to maintain CD4+ T cell counts at a safe level.