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脱氧核糖核酸酶及其在生物医学中的应用。

Deoxyribonucleases and Their Applications in Biomedicine.

机构信息

Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, 3500 Krems, Austria.

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia.

出版信息

Biomolecules. 2020 Jul 11;10(7):1036. doi: 10.3390/biom10071036.

Abstract

Extracellular DNA, also called cell-free DNA, released from dying cells or activated immune cells can be recognized by the immune system as a danger signal causing or enhancing inflammation. The cleavage of extracellular DNA is crucial for limiting the inflammatory response and maintaining homeostasis. Deoxyribonucleases (DNases) as enzymes that degrade DNA are hypothesized to play a key role in this process as a determinant of the variable concentration of extracellular DNA. DNases are divided into two families-DNase I and DNase II, according to their biochemical and biological properties as well as the tissue-specific production. Studies have shown that low DNase activity is both, a biomarker and a pathogenic factor in systemic lupus erythematosus. Interventional experiments proved that administration of exogenous DNase has beneficial effects in inflammatory diseases. Recombinant human DNase reduces mucus viscosity in lungs and is used for the treatment of patients with cystic fibrosis. This review summarizes the currently available published data about DNases, their activity as a potential biomarker and methods used for their assessment. An overview of the experiments with systemic administration of DNase is also included. Whether low-plasma DNase activity is involved in the etiopathogenesis of diseases remains unknown and needs to be elucidated.

摘要

细胞外 DNA,也称为无细胞 DNA,由死亡细胞或激活的免疫细胞释放,可以被免疫系统识别为危险信号,导致或增强炎症。细胞外 DNA 的切割对于限制炎症反应和维持体内平衡至关重要。核酸酶(DNase)作为降解 DNA 的酶,被假设在这个过程中发挥关键作用,是细胞外 DNA 浓度变化的决定因素。根据其生化和生物学特性以及组织特异性产生,DNase 分为两类-DNase I 和 DNase II。研究表明,低 DNase 活性既是全身性红斑狼疮的生物标志物又是致病因素。介入性实验证明,外源性 DNase 的给药在炎症性疾病中有有益的效果。重组人 DNAse 可降低肺部粘液的粘度,用于治疗囊性纤维化患者。本综述总结了目前关于 DNase 的可用发表数据,包括其作为潜在生物标志物的活性及其评估方法。还包括了全身性给予 DNAse 的实验概述。血浆中低 DNase 活性是否参与疾病的病因发病机制尚不清楚,需要进一步阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8025/7407206/fc255c74239b/biomolecules-10-01036-g001.jpg

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