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QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation
Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeutic effec...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366503/ https://www.ncbi.nlm.nih.gov/pubmed/37496671 http://dx.doi.org/10.1016/j.isci.2023.107268 |
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author | Xu, Si-Yi Jia, Jun-Qiu Sun, Min Bao, Xin-Yu Xia, Sheng-Nan Shu, Shu Liu, Pin-yi Ji, Sen-lin Ye, Lei Cao, Xiang Xu, Yun |
author_facet | Xu, Si-Yi Jia, Jun-Qiu Sun, Min Bao, Xin-Yu Xia, Sheng-Nan Shu, Shu Liu, Pin-yi Ji, Sen-lin Ye, Lei Cao, Xiang Xu, Yun |
author_sort | Xu, Si-Yi |
collection | PubMed |
description | Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeutic effect of QHRD106 in ischemic stroke and its possible mechanism. We found that QHRD106 treatment alleviated brain injury after stroke via bradykinin (BK) receptor B2 (B2R) instead of BK receptor B1 (B1R). Mechanistically, QHRD106 reduced high-mobility group box 1 (HMGB1)-induced apoptosis and inflammation after ischemic stroke in vivo and in vitro. Moreover, we confirmed that QHRD106 reduced the level of acetylated HMGB1 and reduced the binding between heat shock protein 90 alpha family class A member 1 (HSP90AA1) and HMGB1, thus inhibiting the translocation and release of HMGB1. In summary, these findings indicate that QHRD106 treatment has therapeutic potential for cerebral ischemic stroke. |
format | Online Article Text |
id | pubmed-10366503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103665032023-07-26 QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation Xu, Si-Yi Jia, Jun-Qiu Sun, Min Bao, Xin-Yu Xia, Sheng-Nan Shu, Shu Liu, Pin-yi Ji, Sen-lin Ye, Lei Cao, Xiang Xu, Yun iScience Article Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeutic effect of QHRD106 in ischemic stroke and its possible mechanism. We found that QHRD106 treatment alleviated brain injury after stroke via bradykinin (BK) receptor B2 (B2R) instead of BK receptor B1 (B1R). Mechanistically, QHRD106 reduced high-mobility group box 1 (HMGB1)-induced apoptosis and inflammation after ischemic stroke in vivo and in vitro. Moreover, we confirmed that QHRD106 reduced the level of acetylated HMGB1 and reduced the binding between heat shock protein 90 alpha family class A member 1 (HSP90AA1) and HMGB1, thus inhibiting the translocation and release of HMGB1. In summary, these findings indicate that QHRD106 treatment has therapeutic potential for cerebral ischemic stroke. Elsevier 2023-07-03 /pmc/articles/PMC10366503/ /pubmed/37496671 http://dx.doi.org/10.1016/j.isci.2023.107268 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Xu, Si-Yi Jia, Jun-Qiu Sun, Min Bao, Xin-Yu Xia, Sheng-Nan Shu, Shu Liu, Pin-yi Ji, Sen-lin Ye, Lei Cao, Xiang Xu, Yun QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
title | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
title_full | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
title_fullStr | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
title_full_unstemmed | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
title_short | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
title_sort | qhrd106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366503/ https://www.ncbi.nlm.nih.gov/pubmed/37496671 http://dx.doi.org/10.1016/j.isci.2023.107268 |
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