Academic Journal
PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
| العنوان: | PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection |
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| المؤلفون: | Wang Yun, Xu Yi, Zhao Tun, Ma Ya-Jun, Qin Wei, Hu Wen-Li |
| المصدر: | Open Life Sciences, Vol 19, Iss 1, Pp 637-53 (2024) |
| بيانات النشر: | De Gruyter, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | intensive care unit- acquired weakness, mir-542, atg5, cellular autophagy, mitochondrial damage, Biology (General), QH301-705.5 |
| الوصف: | Intensive care unit-acquired weakness (ICU-AW) is prevalent in critical care, with limited treatment options. Certain microRNAs, like miR-542, are highly expressed in ICU-AW patients. This study investigates the regulatory role and mechanisms of miR-542 in ICU-AW and explores the clinical potential of miR-542 inhibitors. ICU-AW models were established in C57BL/6 mice through cecal ligation and puncture (CLP) and in mouse C2C12 myoblasts through TNF-α treatment. In vivo experiments demonstrated decreased muscle strength, muscle fiber atrophy, widened intercellular spaces, and increased miR-542-3p/5p expression in ICU-AW mice model. In vitro experiments indicated suppressed ATG5, ATG7 and LC3II/I, elevated MDA and ROS levels, decreased SOD levels, and reduced MMP in the model group. Similar to animal experiments, the expression of miR-542-3p/5p was upregulated. Gel electrophoresis explored the binding of polyethyleneimine/mesoporous silica nanoparticles (PEI/MMNs) to locked nucleic acid (LNA) miR-542 inhibitor (LNA-542). PEI/MMNs@LNA-542 with positive charge (3.03 ± 0.363 mV) and narrow size (206.94 ± 6.19 nm) were characterized. Immunofluorescence indicated significant internalization with no apparent cytotoxicity. Biological activity, examined through intraperitoneal injection, showed that PEI/MMNs@LNA-542 alleviated muscle strength decline, restored fiber damage, and recovered mitochondrial injury in mice. In conclusion, PEI/MMNs nanoparticles effectively delivered LNA-542, targeting ATG5 to inhibit autophagy and alleviate mitochondrial damage, thereby improving ICU-AW. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2391-5412 2022-0952 |
| Relation: | https://doaj.org/toc/2391-5412 |
| DOI: | 10.1515/biol-2022-0952 |
| URL الوصول: | https://doaj.org/article/66d5bc5a804242149518bda38c6b14d5 |
| رقم الانضمام: | edsdoj.66d5bc5a804242149518bda38c6b14d5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23915412 20220952 |
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| DOI: | 10.1515/biol-2022-0952 |