Advanced Science
·
2026
·
IF 14.1
Menghao Qiao,Liqun Zhou,Minhua Zhou,Yu Fang,Haiying Mai,Lingbo Cao,Kun Xu,Yuan Sang,Minyi Chen,Jiewei Huang,Peiyi Huang,Zhipeng Yan,Chao Wang,Zhangshuai Dai,Dichun Huang,Ronghan He,Lijuan Pang,Yunmiao Guo,Ting Gang Chew,Junqi Huang
Ferroptosis is an iron-dependent form of programmed cell death governed by redox homeostasis. Although Ezrin, Radixin, and Moesin (ERM) proteins are established membrane-actin cytoskeleton linkers, their role in ferroptosis remains unexplored. Here, ERM proteins are identified as modulators of erastin-induced ferroptosis. In human fibrosarcoma HT-1080 cells, pharmacological inhibition of ERM phosphorylation, knockdown of individual ERM members, or overexpression of a phospho-deficient Ezrin mutant (T567A) consistently attenuated ferroptosis, whereas wild-type ERM overexpression enhances ferroptosis susceptibility. Mechanistically, ERM inhibition leads to F-actin depolymerization accompanied by a modest rise in reactive oxygen species (ROS). F-actin stabilization prevents this ROS surge and restores ferroptotic sensitivity, whereas its depolymerization mimics the protective effect of ERM inhibition. ROS elevation triggers KEAP1 degradation, stabilizing NRF2 and promoting its nuclear translocation. Activated nuclear NRF2 induces antioxidant genes, particularly HMOX1 , a key effector of heme catabolism that enhances redox buffering and limits lipid peroxidation, ultimately conferring resistance to ferroptosis. The protective effects of ERM inhibition are further validated in ferroptosis-relevant ex vivo and in vivo models. Notably, other pro-oxidants similarly attenuate ferroptosis at appropriate concentrations. Together, these results establish ERM proteins as regulators of ferroptosis and reveal an underappreciated group of ferroptosis inhibitors that engage ROS-NRF2-mediated redox-adaptation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Rui Su,Wei Liu,Gang Shi,Dongling Chen,Lihua Yan,Qian Li,Haichao Ni,Meili Yu,Liang Xu
Hyperbilirubinemia is primarily treated through hemoperfusion, a process that utilizes biomaterials as adsorbents to eliminate excessive bilirubin from the bloodstream. However, extracorporeal circuits are prone to thrombus formation due to the frequent use of blood-contacting devices, potentially leading to treatment failure and adverse clinical outcomes. In this study, using a resin substance treated with sulfated polysaccharides (GLU-ERM-0100), we present a reliable and safe approach for removing excessive bilirubin from blood. The resin’s pore size facilitates bilirubin adsorption, while sulfonic and hydroxyl groups incorporated within the material enable like-heparinization. GLU-ERM-0100 serves as a temporary blood-thinning agent, binding coagulation factors in the extracorporeal circuit, thereby eliminating the need for conventional anticoagulant medications. Both in vitro and animal studies demonstrate the material’s exceptional bilirubin adsorption capacity and effective anticoagulation properties.
研究领域:
医学工程
·
血液学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Lei Lin,Liming Xu,Weijie Sun,Lili Liang,Xiaoliang Qi,Yun-e Zhao
Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.
研究领域:
眼科学
·
细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）