Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.

Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.
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氧化岩纳米颗粒与microRNA-146A校正机理的糖尿病伤口愈合机理。

DOI:
10.1016/j.nano.2021.102483
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发表时间:
2022-03
影响因子:
5.4
通讯作者:
Zgheib, Carlos
Zgheib, Carlos
中科院分区:
医学2区
文献类型:
--
作者:
Dewberry, Lindel C.;Niemiec, Stephen M.;Hilton, Sarah A.;Louiselle, Amanda E.;Singh, Sushant;Sakthivel, Tamil S.;Hu, Junyi;Seal, Sudipta;Liechty, Kenneth W.;Zgheib, Carlos

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糖尿病伤口代表了显著的医疗保健负担,并且其特征在于由于增加的氧化应激和持续性炎症而导致的伤口愈合受损。我们已经表明,通过氧化铈纳米颗粒(CNP)与微小RNA(miR)-146 a缀合合成的CNP-miR 146 a改善糖尿病伤口愈合。CNP是作为自由基清除剂的二价金属氧化物,而miR 146 a抑制促炎NFκB途径,因此CNP-miR 146 a在调节氧化应激和炎症中具有协同作用。在这项研究中,我们通过检查炎症、氧化应激、纤维化和血管生成标志物的免疫组织化学和基因表达分析来确定CNP-miR 146 a改善糖尿病伤口愈合的机制。我们已经发现,皮内注射CNP-miR 146 a增加伤口胶原蛋白,增强血管生成,并降低炎症和氧化应激,最终促进糖尿病伤口的更快闭合。糖尿病伤口的特征在于增加的炎症和氧化应激,这导致血管生成受损和伤口愈合延迟。CNP-miR 146 a是清除ROS的氧化铈纳米颗粒(CNP)与抗炎microRNA(miR)-146a的结合物,协同降低炎症和氧化应激,改善血管生成和胶原沉积的组织学证据,并最终加速伤口闭合。
Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a, improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds. Diabetic wounds are characterized by increased inflammation and oxidative stress, which results in impaired angiogenesis and delayed wound healing. CNP-miR146a, the conjugation of ROS scavenging cerium oxide nanoparticles (CNP) to anti-inflammatory microRNA (miR)-146a, synergistically lowers inflammation and oxidative stress, improving histologic evidence of angiogenesis and collagen deposition, and ultimately accelerating wound closure.
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