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构建合成DNA-组蛋白网络作为生物医学研究的细胞外陷阱模型。

Constructing of Synthetic DNA-Histone Networks as Extracellular Trap Model for Biomedical Research.

作者信息

Shmeleva E V, Basyreva L Yu, Vakhrusheva T V, Sokolov A V, Gusev S A, Panasenko O M, Sergienko V I

机构信息

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical-Biological Agency of Russia, Moscow, Russia.

Institute of Experimental Medicine, St. Petersburg, Russia.

出版信息

Bull Exp Biol Med. 2025 Aug 29. doi: 10.1007/s10517-025-06473-0.

DOI:10.1007/s10517-025-06473-0
PMID:40879924
Abstract

Extracellular traps (ETs) released during ETosis of various blood cells not only participate in host defense against pathogenic microorganisms, but also play an essential role in diverse pathological processes. It should be noted that ETs are heterogeneous by their structure; therefore, for studying their pathophysiological effects, it is extremely important to create model ETs with strictly controlled composition and structure. We propose an approach that allows creating model mesh structures based on DNA and histones (DNA-histone networks, DHN), which can be considered as model ETs. It has been shown that the structure of DHN depends on the DNA/histone weight ratio. The possibility of incorporating myeloperoxidase that can be present in native ETs, into DHN has been demonstrated. The creation of DHN with controlled composition and structure will presumably allow assessing the specificity of enzyme systems involved in the degradation of native ETs. In addition, these heterogeneous DHN can be used to study the relationship between ET structure and ET-induced thrombosis or their antimicrobial activity.

摘要

各种血细胞在胞外诱捕作用过程中释放的细胞外陷阱(ETs)不仅参与宿主对病原微生物的防御,还在多种病理过程中发挥重要作用。需要注意的是,ETs的结构具有异质性;因此,为了研究它们的病理生理效应,创建具有严格可控组成和结构的模型ETs极其重要。我们提出了一种方法,该方法能够基于DNA和组蛋白创建模型网状结构(DNA-组蛋白网络,DHN),其可被视为模型ETs。研究表明,DHN的结构取决于DNA/组蛋白的重量比。已经证实了将天然ETs中可能存在的髓过氧化物酶纳入DHN的可能性。创建具有可控组成和结构的DHN大概将有助于评估参与天然ETs降解的酶系统的特异性。此外,这些异质性的DHN可用于研究ET结构与ET诱导的血栓形成或其抗菌活性之间的关系。

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本文引用的文献

1
Hypochlorous Acid-Modified Serum Albumin Causes NETosis in the Whole Blood Ex Vivo and in Isolated Neutrophils.次氯酸修饰的血清白蛋白导致全血离体和分离的中性粒细胞发生 NETosis。
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The Effect of Vitamin D3 on Neutrophil Extracellular Trap Formation in High-Glucose Conditions.维生素 D3 对高糖环境中中性粒细胞胞外诱捕网形成的影响。
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Targeting NETs using dual-active DNase1 variants.
利用双活性 DNase1 变体靶向 NETs。
Front Immunol. 2023 May 23;14:1181761. doi: 10.3389/fimmu.2023.1181761. eCollection 2023.
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Neutrophil Extracellular Traps Delay Diabetic Wound Healing by Inducing Endothelial-to-Mesenchymal Transition via the Hippo pathway.中性粒细胞胞外诱捕网通过 Hippo 通路诱导血管内皮细胞向间充质细胞转化而延缓糖尿病创面愈合。
Int J Biol Sci. 2023 Jan 1;19(1):347-361. doi: 10.7150/ijbs.78046. eCollection 2023.
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Methylglyoxal-Modified Human Serum Albumin Binds to Leukocyte Myeloperoxidase and Inhibits its Enzymatic Activity.甲基乙二醛修饰的人血清白蛋白与白细胞髓过氧化物酶结合并抑制其酶活性。
Antioxidants (Basel). 2022 Nov 16;11(11):2263. doi: 10.3390/antiox11112263.
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Effect of Vitamin D3 in combination with Omega-3 Polyunsaturated Fatty Acids on NETosis in Type 2 Diabetes Mellitus Patients.维生素 D3 联合欧米伽-3 多不饱和脂肪酸对 2 型糖尿病患者中性粒细胞胞外诱捕网形成的影响。
Oxid Med Cell Longev. 2021 Oct 22;2021:8089696. doi: 10.1155/2021/8089696. eCollection 2021.
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Extracellular Trap by Blood Cells: Clinical Implications.血细胞释放的细胞外陷阱:临床意义。
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Extracellular Trap-Mimicking DNA-Histone Mesostructures Synergistically Activate Dendritic Cells.细胞外诱捕网样 DNA-组蛋白介孔结构协同激活树突状细胞。
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Antimicrobial Microwebs of DNA-Histone Inspired from Neutrophil Extracellular Traps.基于中性粒细胞胞外诱捕网的 DNA-组蛋白抗菌微网
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