Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes

Autores
Cao, Qiuhua; Gao, Xinghua; Lin, Yanting; Yue, Chongxiu; Wang, Yue; Quan, Fei; Zhang, Zixuan; Liu, Xiaoxuan; Lu, Yuan; Zhan, Yanling; Yang, Hongbao; Li, Xianjing; Qin, Di; Birnbaumer, Lutz; Hao, Kun; Yang, Yong
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Cao, Qiuhua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Cao, Qiuhua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Gao, Xinghua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Gao, Xinghua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Lin, Yanting. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Lin, Yanting. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Yue, Chongxiu. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Yue, Chongxiu. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Yue. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Wang, Yue. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Quan, Fei. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Quan, Fei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zhang, Zixuan. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Zhang, Zixuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Liu, Xiaoxuan. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Liu, Xiaoxuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Lu, Yuan.China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Lu, Yuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zhan, Yanling. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Zhan, Yanling. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Yang, Hongbao. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Yang, Hongbao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Li, Xianjing. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Li, Xianjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Qin, Di. Nanjing sport institute. School of Sports and Health; China
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neurobiology; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Hao, Kun. China Pharmaceutical University. Key Lab of Drug Metabolism & Pharmacokinetics; China
Fil: Yang, Yong. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Background: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, notoriously challenging to treat. Previous studies have found a positive correlation between thymic atrophy and colitis severity. It was, therefore, worthwhile to investigate the effect of thymopentin (TP5), a synthetic pentapeptide corresponding to the active domain of the thymopoietin, on colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis mice were treated with TP5 by subcutaneous injection. Body weight, colon length, colon weight, immune organ index, disease activity index (DAI) score, and the peripheral blood profile were examined. The immune cells of the spleen and colon were analyzed by flow cytometry. Histology was performed on isolated colon tissues for cytokine analysis. Bacterial DNA was extracted from mouse colonic feces to assess the intestinal microbiota. Intestinal lamina propria mononuclear cells (LPMCs), HCT116, CT26, and splenocytes were cultured and treated with TP5. Results: TP5 treatment increased the body weight and colon length, decreased the DAI score, and restored colon architecture of colitic mice. TP5 also decreased the infiltration of immune cells and expression levels of pro-inflammatory cytokines such as IL-6. Importantly, the damaged thymus and compromised lymphocytes in peripheral blood were significantly restored by TP5. Also, the production of IL-22, both in innate and adaptive lymphoid cells, was triggered by TP5. Given the critical role of IL-22 in mucosal host defense, we tested the effect of TP5 on mucus barrier and gut microbiota and found that the number of goblet cells and the level of Mucin-2 expression were restored, and the composition of the gut microbiome was normalized after TP5 treatment. The critical role of IL-22 in the protective effect of TP5 on colitis was further confirmed by administering the anti-IL-22 antibody (αIL-22), which completely abolished the effect of TP5. Furthermore, TP5 significantly increased the expression level of retinoic acid receptor-related orphan receptor γ (RORγt), a transcription factor for IL-22. Consistent with this, RORγt inhibitor abrogated the upregulation of IL-22 induced by TP5. Conclusion: TP5 exerts a protective effect on DSS-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes. This study delineates TP5 as an immunomodulator that may be a potential drug for the treatment of UC.
Fuente
Theranostics. 2019, 9(25)
Materia
COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/9854

id RIUCA_b6597506e9a8b1a6fa6507a306f1e001
oai_identifier_str oai:ucacris:123456789/9854
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytesCao, QiuhuaGao, XinghuaLin, YantingYue, ChongxiuWang, YueQuan, FeiZhang, ZixuanLiu, XiaoxuanLu, YuanZhan, YanlingYang, HongbaoLi, XianjingQin, DiBirnbaumer, LutzHao, KunYang, YongCOLITISTIMOPENTINATRATAMIENTO MEDICOLINFOCITOSFil: Cao, Qiuhua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Cao, Qiuhua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Gao, Xinghua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Gao, Xinghua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Lin, Yanting. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Lin, Yanting. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Yue, Chongxiu. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Yue, Chongxiu. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Yue. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Wang, Yue. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Quan, Fei. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Quan, Fei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Zhang, Zixuan. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Zhang, Zixuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Liu, Xiaoxuan. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Liu, Xiaoxuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Lu, Yuan.China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Lu, Yuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Zhan, Yanling. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Zhan, Yanling. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Yang, Hongbao. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Yang, Hongbao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Li, Xianjing. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Li, Xianjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Qin, Di. Nanjing sport institute. School of Sports and Health; ChinaFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neurobiology; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Hao, Kun. China Pharmaceutical University. Key Lab of Drug Metabolism & Pharmacokinetics; ChinaFil: Yang, Yong. China Pharmaceutical University. State Key Laboratory of Natural Medicines; ChinaFil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaBackground: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, notoriously challenging to treat. Previous studies have found a positive correlation between thymic atrophy and colitis severity. It was, therefore, worthwhile to investigate the effect of thymopentin (TP5), a synthetic pentapeptide corresponding to the active domain of the thymopoietin, on colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis mice were treated with TP5 by subcutaneous injection. Body weight, colon length, colon weight, immune organ index, disease activity index (DAI) score, and the peripheral blood profile were examined. The immune cells of the spleen and colon were analyzed by flow cytometry. Histology was performed on isolated colon tissues for cytokine analysis. Bacterial DNA was extracted from mouse colonic feces to assess the intestinal microbiota. Intestinal lamina propria mononuclear cells (LPMCs), HCT116, CT26, and splenocytes were cultured and treated with TP5. Results: TP5 treatment increased the body weight and colon length, decreased the DAI score, and restored colon architecture of colitic mice. TP5 also decreased the infiltration of immune cells and expression levels of pro-inflammatory cytokines such as IL-6. Importantly, the damaged thymus and compromised lymphocytes in peripheral blood were significantly restored by TP5. Also, the production of IL-22, both in innate and adaptive lymphoid cells, was triggered by TP5. Given the critical role of IL-22 in mucosal host defense, we tested the effect of TP5 on mucus barrier and gut microbiota and found that the number of goblet cells and the level of Mucin-2 expression were restored, and the composition of the gut microbiome was normalized after TP5 treatment. The critical role of IL-22 in the protective effect of TP5 on colitis was further confirmed by administering the anti-IL-22 antibody (αIL-22), which completely abolished the effect of TP5. Furthermore, TP5 significantly increased the expression level of retinoic acid receptor-related orphan receptor γ (RORγt), a transcription factor for IL-22. Consistent with this, RORγt inhibitor abrogated the upregulation of IL-22 induced by TP5. Conclusion: TP5 exerts a protective effect on DSS-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes. This study delineates TP5 as an immunomodulator that may be a potential drug for the treatment of UC.Ivyspring International Publisher2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/98541838-764010.7150/thno.3501531695782Cao, Q. et al. Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes [en línea]. Theranostics. 2019, 9(25). doi:10.7150/thno.35015 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9854Theranostics. 2019, 9(25)reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:57:19Zoai:ucacris:123456789/9854instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:57:19.483Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
spellingShingle Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
Cao, Qiuhua
COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
title_short Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_full Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_fullStr Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_full_unstemmed Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_sort Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
dc.creator.none.fl_str_mv Cao, Qiuhua
Gao, Xinghua
Lin, Yanting
Yue, Chongxiu
Wang, Yue
Quan, Fei
Zhang, Zixuan
Liu, Xiaoxuan
Lu, Yuan
Zhan, Yanling
Yang, Hongbao
Li, Xianjing
Qin, Di
Birnbaumer, Lutz
Hao, Kun
Yang, Yong
author Cao, Qiuhua
author_facet Cao, Qiuhua
Gao, Xinghua
Lin, Yanting
Yue, Chongxiu
Wang, Yue
Quan, Fei
Zhang, Zixuan
Liu, Xiaoxuan
Lu, Yuan
Zhan, Yanling
Yang, Hongbao
Li, Xianjing
Qin, Di
Birnbaumer, Lutz
Hao, Kun
Yang, Yong
author_role author
author2 Gao, Xinghua
Lin, Yanting
Yue, Chongxiu
Wang, Yue
Quan, Fei
Zhang, Zixuan
Liu, Xiaoxuan
Lu, Yuan
Zhan, Yanling
Yang, Hongbao
Li, Xianjing
Qin, Di
Birnbaumer, Lutz
Hao, Kun
Yang, Yong
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
topic COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
dc.description.none.fl_txt_mv Fil: Cao, Qiuhua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Cao, Qiuhua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Gao, Xinghua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Gao, Xinghua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Lin, Yanting. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Lin, Yanting. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Yue, Chongxiu. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Yue, Chongxiu. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Yue. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Wang, Yue. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Quan, Fei. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Quan, Fei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zhang, Zixuan. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Zhang, Zixuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Liu, Xiaoxuan. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Liu, Xiaoxuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Lu, Yuan.China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Lu, Yuan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zhan, Yanling. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Zhan, Yanling. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Yang, Hongbao. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Yang, Hongbao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Li, Xianjing. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Li, Xianjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Qin, Di. Nanjing sport institute. School of Sports and Health; China
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neurobiology; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Hao, Kun. China Pharmaceutical University. Key Lab of Drug Metabolism & Pharmacokinetics; China
Fil: Yang, Yong. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
Fil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Background: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, notoriously challenging to treat. Previous studies have found a positive correlation between thymic atrophy and colitis severity. It was, therefore, worthwhile to investigate the effect of thymopentin (TP5), a synthetic pentapeptide corresponding to the active domain of the thymopoietin, on colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis mice were treated with TP5 by subcutaneous injection. Body weight, colon length, colon weight, immune organ index, disease activity index (DAI) score, and the peripheral blood profile were examined. The immune cells of the spleen and colon were analyzed by flow cytometry. Histology was performed on isolated colon tissues for cytokine analysis. Bacterial DNA was extracted from mouse colonic feces to assess the intestinal microbiota. Intestinal lamina propria mononuclear cells (LPMCs), HCT116, CT26, and splenocytes were cultured and treated with TP5. Results: TP5 treatment increased the body weight and colon length, decreased the DAI score, and restored colon architecture of colitic mice. TP5 also decreased the infiltration of immune cells and expression levels of pro-inflammatory cytokines such as IL-6. Importantly, the damaged thymus and compromised lymphocytes in peripheral blood were significantly restored by TP5. Also, the production of IL-22, both in innate and adaptive lymphoid cells, was triggered by TP5. Given the critical role of IL-22 in mucosal host defense, we tested the effect of TP5 on mucus barrier and gut microbiota and found that the number of goblet cells and the level of Mucin-2 expression were restored, and the composition of the gut microbiome was normalized after TP5 treatment. The critical role of IL-22 in the protective effect of TP5 on colitis was further confirmed by administering the anti-IL-22 antibody (αIL-22), which completely abolished the effect of TP5. Furthermore, TP5 significantly increased the expression level of retinoic acid receptor-related orphan receptor γ (RORγt), a transcription factor for IL-22. Consistent with this, RORγt inhibitor abrogated the upregulation of IL-22 induced by TP5. Conclusion: TP5 exerts a protective effect on DSS-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes. This study delineates TP5 as an immunomodulator that may be a potential drug for the treatment of UC.
description Fil: Cao, Qiuhua. China Pharmaceutical University. State Key Laboratory of Natural Medicines; China
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://repositorio.uca.edu.ar/handle/123456789/9854
1838-7640
10.7150/thno.35015
31695782
Cao, Q. et al. Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes [en línea]. Theranostics. 2019, 9(25). doi:10.7150/thno.35015 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9854
url https://repositorio.uca.edu.ar/handle/123456789/9854
identifier_str_mv 1838-7640
10.7150/thno.35015
31695782
Cao, Q. et al. Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes [en línea]. Theranostics. 2019, 9(25). doi:10.7150/thno.35015 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9854
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Ivyspring International Publisher
publisher.none.fl_str_mv Ivyspring International Publisher
dc.source.none.fl_str_mv Theranostics. 2019, 9(25)
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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