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Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm
In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous po...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026257/ https://www.ncbi.nlm.nih.gov/pubmed/33846686 http://dx.doi.org/10.1016/j.nantod.2021.101149 |
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author | Kim, Hyelim Lee, Han Sol Ahn, June Hong Hong, Kyung Soo Jang, Jong Geol An, Jiseon Mun, Yong-Hyeon Yoo, So-Yeol Choi, Yoon Jung Yun, Mi-Young Song, Gyu Yong Joo, Jinmyoung Na, Dong Hee Kim, Hong Nam Park, Hee Ho Lee, Jae-Young Lee, Wonhwa |
author_facet | Kim, Hyelim Lee, Han Sol Ahn, June Hong Hong, Kyung Soo Jang, Jong Geol An, Jiseon Mun, Yong-Hyeon Yoo, So-Yeol Choi, Yoon Jung Yun, Mi-Young Song, Gyu Yong Joo, Jinmyoung Na, Dong Hee Kim, Hong Nam Park, Hee Ho Lee, Jae-Young Lee, Wonhwa |
author_sort | Kim, Hyelim |
collection | PubMed |
description | In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm. |
format | Online Article Text |
id | pubmed-8026257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Author(s). Published by Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80262572021-04-08 Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm Kim, Hyelim Lee, Han Sol Ahn, June Hong Hong, Kyung Soo Jang, Jong Geol An, Jiseon Mun, Yong-Hyeon Yoo, So-Yeol Choi, Yoon Jung Yun, Mi-Young Song, Gyu Yong Joo, Jinmyoung Na, Dong Hee Kim, Hong Nam Park, Hee Ho Lee, Jae-Young Lee, Wonhwa Nano Today Article In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm. The Author(s). Published by Elsevier Ltd. 2021-06 2021-04-08 /pmc/articles/PMC8026257/ /pubmed/33846686 http://dx.doi.org/10.1016/j.nantod.2021.101149 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Kim, Hyelim Lee, Han Sol Ahn, June Hong Hong, Kyung Soo Jang, Jong Geol An, Jiseon Mun, Yong-Hyeon Yoo, So-Yeol Choi, Yoon Jung Yun, Mi-Young Song, Gyu Yong Joo, Jinmyoung Na, Dong Hee Kim, Hong Nam Park, Hee Ho Lee, Jae-Young Lee, Wonhwa Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm |
title | Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm |
title_full | Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm |
title_fullStr | Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm |
title_full_unstemmed | Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm |
title_short | Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm |
title_sort | lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of covid-19-associated cytokine storm |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026257/ https://www.ncbi.nlm.nih.gov/pubmed/33846686 http://dx.doi.org/10.1016/j.nantod.2021.101149 |
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