从“一气周流”论述细胞焦亡与代谢综合征血管内皮损伤的相关性

“一气周流”是中医经典理论,其核心思想认为中气(脾胃之气)是整个气机运转的枢纽。脾胃虚弱,肝气郁结,水谷精微运化疏泄失常,日久痰浊瘀血内生,积聚于血管,引起代谢综合征血管内皮损伤。临床及实验研究均证实健脾疏肝方剂柴芪汤对代谢综合征及相关血管内皮损伤具有较好改善作用。细胞焦亡是一种促炎性程序性细胞死亡方式,在血管内皮炎症反应中具有重要作用,这一过程类似于中医“痰瘀浊毒”的积聚。基于“一气周流”理论探讨细胞焦亡与代谢综合征血管内皮损伤的机制,为中医经典理论和中医药防治代谢综合征血管并发症提供理论依据。     

细胞焦亡对肝癌发生发展的影响及中医药的干预作用

细胞焦亡是一种新发现的程序性细胞死亡方式,在肝癌中发挥着关键作用。故拟基于细胞焦亡的分子机制及其在肝癌发病机制中的作用进行深入分析,并结合中医药在调节焦亡肝癌发展过程中的作用进行探讨,以期为临床提供新的治疗思路。     

恩格列净通过抑制细胞焦亡改善糖尿病小鼠肾脏损伤

目的:研究恩格列净(empagliflozin)对db/db小鼠肾脏损伤的保护作用及其潜在作用机制。方法:db/db小鼠随机分为糖尿病肾病组(db/db组)和恩格列净治疗组(Empa组,恩格列净10 mg·kg -1·d -1灌胃),C57BL/6J小鼠作为正常对照组。干预3个月,检测血清生化、...     

焦亡信号通路炎症小体与中枢神经系统疾病研究进展

焦亡是一种新发现并证实与炎症相关的细胞死亡方式,其特征为依赖于半胱天冬氨酸蛋白酶-1(caspase-1)的细胞程序性死亡,并伴有促炎症因子的释放,主要为白细胞介素1β和IL-18.虽然焦亡与坏死和凋亡有相似之处,但它们是迥然不同的生物学过程.越来越多的研究发现,焦亡相关信号通路在中枢神经系统疾病中起重要作用,包括急性脑感染、神经变性疾病、急性无菌性脑损伤和慢性无菌性中枢神经系统炎症.     

Potassium efflux fires the canon: Potassium efflux as a common trigger for canonical and noncanonical NLRP3 pathways

Murine caspase‐11 and its human orthologues, caspase‐4 and caspase‐5, activate an inflammatory response following cytoplasmic recognition of cell wall constituents from Gram‐negative bacteria, such as LPS. This inflammatory response involves pyroptotic cell death and the concomitant release of IL‐1α, as well as the production of IL‐1β and IL‐18 through the noncanonical NLR family, pyrin domain containing 3 (NLRP3) pathway. This commentary discusses three papers in this issue of the European Journal of Immunology that advance our understanding of the roles of caspase‐11, ‐4, and ‐5 in the noncanonical pathway. By utilizing the new gene editing technique, clustered regularly interspaced short palindromic repeats (CRISPR), as well as sensitive cell imaging techniques, these papers establish that cytoplasmic LPS‐dependent IL‐1β production requires the NLRP3 inflammasome and that its activation is dependent on K⁺ efflux, whereas IL‐1α release and pyroptotic cell death pathways are NLRP3‐independent. These findings expand on previous research implicating K⁺ efflux as the principal trigger for NLRP3 activation and suggest that canonical and noncanonical NLRP3 pathways are not as dissimilar as first thought.     

Methods for monitoring cancer cell pyroptosis

Pyroptosis is a form of proinflammatory cell death that depends on the gasdermin family of proteins. The main features of pyroptosis are altered membrane permeability, cell swelling, membrane rupture, and the ability to mobilize a strong immune response. The relationship between pyroptosis and cancer has become a popular topic in immunological research. Multiple strategies for inducing pyroptosis in cancer cells have been developed for cancer therapy, including chemotherapy, small molecule drugs, and nanomedicines. In this review, we systematically discuss recent advances in research on the mechanisms of pyroptosis, and compare pyroptosis with apoptosis and necroptosis from several aspects. The development of various experimental systems has accompanied rapid progress in this field, but little consensus on monitoring pyroptosis is currently available. We focus on techniques commonly used to monitor pyroptosis, and describe future techniques that may be used to increase our knowledge in this field. Overall, the advancement of pyroptosis detection methods will help researchers to better investigate the relationships between pyroptosis and various cancers, and should provide insights into the use of these promising tools for cancer treatments.     

Inhibition of caspase-1 prolongs survival of mice infected with rabies virus

Rabies virus infects almost all mammals resulting in lethal disease. To date there is no treatment available for symptomatic rabies and there is an urgent need to develop treatment strategies that would prolong survival, thereby providing a window of opportunity for the host to mount a protective immune response. We hypothesized that both virus and excessive immune response contribute to disease and that interfering with both is necessary to prevent lethal disease. Here, we have inhibited the pro-inflammatory response associated with pyroptosis and showed that inhibition of CASP-1 had a beneficial effect on survival time. Our results confirm that some inflammatory responses may be involved in the pathogenesis of severe disease and the results suggest that effective intervention includes inhibition of virus and host response.     

PM2.5 induced lung injury through upregulating ROS-dependent NLRP3 Inflammasome-Mediated Pyroptosis

The main cause of air pollution is PM_2.5, which directly causes lung injury through respiration. Oxidative stress and inflammation are considered to be the key mechanism of cell damage. Pyroptosis is a process of the programmed death of inflammatory cells and as a dangerous endogenous signal, it is widely involved in different inflammatory diseases. However, few studies have been conducted on PM_2.5 exposure and cell pyroptosis. In this study, we aimed to investigate the effect of PM_2.5 on apoptosis, pyroptosis and cell cycle arrest regulated by reactive oxygen species production. Balb/c mice were exposed to PM_2.5 dynamically and verified by the RAW264.7 cells in vitro. The results showed the activation of NF-κB and NLRP3 inflammasome and the release of IL-1β and reactive oxygen species were caused by exposure to PM_2.5. The maturation of IL-1β relied on Caspase-1, and the active Caspase-1 was related to cell pyroptosis. Oxidative stress, inflammation, apoptosis and pyroptosis all affected the cell cycle. This study describes a potentially important mechanism of PM_2.5-induced lung damage that PM_2.5 promotes lung injury via upregulating ROS-NLRP3-mediated the RAW264.7 cells pyroptosis.