Magnesium hexacyanoferrate mitigates sepsis-associated encephalopathy through inhibiting microglial activation and neuronal cuproptosis

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-03-20 DOI:10.1016/j.biomaterials.2025.123279

Yabing Zhang , Juan Xin , Di Zhao , Gezi Chen , Penghao Ji , Panmiao Liu , Hua Wei , Hongwei Wang , Yuzhong Xia , Yong Wang , Zhongyu Wang , Xiangyi Ren , Minfeng Huo , Hai Yu , Jianjun Yang

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Abstract

Sepsis-associated encephalopathy (SAE) is a severe neurological complication stemming from sepsis, characterized by cognitive impairment. The underlying mechanisms involve oxidative stress, neuroinflammation, and disruptions in copper/iron homeostasis. This study introduces magnesium hexacyanoferrate (MgHCF) as a novel compound and explores its therapeutic potential in SAE. Our investigation reveals that MgHCF features intriguing properties in effectively scavenging reactive oxygen species (ROS), and chelating excess copper and iron. Treatment with MgHCF significantly attenuates microglia activation, and protects neuronal cells from oxidative damage and cytotoxicity induced by activated microglia in vitro and in vivo. Furthermore, the cognitive impairment in SAE mice is effectively alleviated by MgHCF treatment, mechanically through a reduction in the copper/iron-responsive histone methylation, and neuronal cuproptosis. These findings suggest MgHCF as a promising therapeutic agent for SAE, targeting the copper/iron signaling pathway to alleviate neuroinflammation, and neuronal cuproptosis.

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六氰合铁酸镁通过抑制小胶质细胞活化和神经元杯突变化缓解败血症相关脑病

脓毒症相关脑病（SAE）是一种由脓毒症引起的严重神经系统并发症，以认知障碍为特征。潜在的机制包括氧化应激、神经炎症和铜/铁稳态的破坏。本研究介绍了一种新型化合物六氰高铁酸镁（MgHCF），并探讨了其在SAE中的治疗潜力。我们的研究表明，MgHCF在有效清除活性氧（ROS）和螯合过量的铜和铁方面具有有趣的特性。在体外和体内实验中，MgHCF可显著减弱小胶质细胞的活化，保护神经元细胞免受活化小胶质细胞引起的氧化损伤和细胞毒性。此外，通过减少铜/铁反应组蛋白甲基化和神经元铜突起，MgHCF治疗可以有效减轻SAE小鼠的认知功能障碍。这些研究结果表明，MgHCF作为一种有前景的SAE治疗药物，靶向铜/铁信号通路，以减轻神经炎症和神经元铜突起。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.