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
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/9854
Ver los metadatos del registro completo
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oai:ucacris:123456789/9854 |
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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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1836638350856945664 |
score |
13.070432 |