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基于单原子催化剂的催化活性氧清除用于通过恢复 ESR1 实现高效银屑病治疗和复发预防。

Single-atom catalysts-based catalytic ROS clearance for efficient psoriasis treatment and relapse prevention via restoring ESR1.

机构信息

Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, Clinical Center For Brain And Spinal Cord Research, School of Medicine, Tongji University, Shanghai, 200092, China.

Shanghai Institute of Ceramics, Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, China.

出版信息

Nat Commun. 2023 Oct 25;14(1):6767. doi: 10.1038/s41467-023-42477-y.

DOI:10.1038/s41467-023-42477-y
PMID:37880231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10600197/
Abstract

Psoriasis is a common inflammatory disease of especially high recurrence rate (90%) which is suffered by approximately 3% of the world population. The overexpression of reactive oxygen species (ROS) plays a critical role in psoriasis progress. Here we show that biomimetic iron single-atom catalysts (FeNO-SACs) with broad-spectrum ROS scavenging capability can be used for psoriasis treatment and relapse prevention via related gene restoration. FeNO-SACs demonstrate attractive multiple enzyme-mimicking activities based on atomically dispersed Fe active structures, which are analogous to those of natural antioxidant enzymes, iron superoxide dismutase, human erythrocyte catalase, and ascorbate peroxidase. Further, in vitro and in vivo experiments show that FeNO-SACs can effectively ameliorate psoriasis-like symptoms and prevent the relapse with augmented efficacy compared with the clinical drug calcipotriol. Mechanistically, estrogen receptor 1 (ESR1) is identified as the core protein upregulated in psoriasis treatment through RNA sequencing and bioinformatic analysis. Together, this study provides a proof of concept of psoriasis catalytic therapy (PCT) and multienzyme-inspired bionics (MIB).

摘要

银屑病是一种常见的炎症性疾病,复发率极高(90%),约占世界人口的 3%。活性氧(ROS)的过度表达在银屑病的进展中起着关键作用。在这里,我们展示了具有广谱 ROS 清除能力的仿生铁单原子催化剂(FeNO-SACs)可以通过相关基因恢复用于治疗银屑病和预防复发。FeNO-SACs 基于原子分散的 Fe 活性结构表现出有吸引力的多种酶模拟活性,类似于天然抗氧化酶、铁超氧化物歧化酶、人红细胞过氧化氢酶和抗坏血酸过氧化物酶的活性。此外,体外和体内实验表明,与临床药物卡泊三醇相比,FeNO-SACs 可以有效改善银屑病样症状并预防复发,疗效增强。从机制上讲,通过 RNA 测序和生物信息学分析,雌激素受体 1(ESR1)被确定为治疗银屑病时上调的核心蛋白。总之,这项研究为银屑病催化治疗(PCT)和多酶仿生(MIB)提供了一个概念验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/601d3ee2bc7a/41467_2023_42477_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/e0489337cc59/41467_2023_42477_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/fb7b2791161a/41467_2023_42477_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/0b9e54380934/41467_2023_42477_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/b85b83430bd7/41467_2023_42477_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/601d3ee2bc7a/41467_2023_42477_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/a54f2181b70f/41467_2023_42477_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/4e4957985bc8/41467_2023_42477_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/d7c5c1ef4b79/41467_2023_42477_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/e0489337cc59/41467_2023_42477_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/fb7b2791161a/41467_2023_42477_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/0b9e54380934/41467_2023_42477_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/b85b83430bd7/41467_2023_42477_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/10600197/601d3ee2bc7a/41467_2023_42477_Fig8_HTML.jpg

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