Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.
Identifieur interne : 000013 ( Main/Exploration ); précédent : 000012; suivant : 000014Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.
Auteurs : Hong-Xia Zhou [République populaire de Chine] ; Run-Feng Li [République populaire de Chine] ; Yi-Feng Wang [République populaire de Chine] ; Li-Han Shen [République populaire de Chine] ; Li-Hua Cai [République populaire de Chine] ; Yun-Ceng Weng [République populaire de Chine] ; Huan-Rong Zhang [République populaire de Chine] ; Xin-Xin Chen [République populaire de Chine] ; Xiao Wu [République populaire de Chine] ; Rui-Feng Chen [République populaire de Chine] ; Hai-Ming Jiang [République populaire de Chine] ; Caiyun Wang [République populaire de Chine] ; Mingrong Yang [République populaire de Chine] ; Jingguang Lu [République populaire de Chine] ; Xiao-Dong Luo [République populaire de Chine] ; Zhihong Jiang [République populaire de Chine] ; Zi-Feng Yang [République populaire de Chine]Source :
- Phytomedicine : international journal of phytotherapy and phytopharmacology [ 1618-095X ] ; 2020.
Abstract
BACKGROUND
Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection.
PURPOSE
To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection.
METHODS
Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed.
RESULTS
TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model.
CONCLUSION
TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.
DOI: 10.1016/j.phymed.2020.153272
PubMed: 32702592
Affiliations:
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China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dongguan People's Hospital, Dongguan, 523000</wicri:regionArea><wicri:noRegion>523000</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Li Hua" sort="Cai, Li Hua" uniqKey="Cai L" first="Li-Hua" last="Cai">Li-Hua Cai</name><affiliation wicri:level="1"><nlm:affiliation>Dongguan People's Hospital, Dongguan, 523000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dongguan People's Hospital, Dongguan, 523000</wicri:regionArea><wicri:noRegion>523000</wicri:noRegion></affiliation></author><author><name sortKey="Weng, Yun Ceng" sort="Weng, Yun Ceng" uniqKey="Weng Y" first="Yun-Ceng" last="Weng">Yun-Ceng Weng</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Huan Rong" sort="Zhang, Huan Rong" uniqKey="Zhang H" first="Huan-Rong" last="Zhang">Huan-Rong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Becton, Dickinson and Company, 510000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Becton, Dickinson and Company, 510000</wicri:regionArea><wicri:noRegion>510000</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xin Xin" sort="Chen, Xin Xin" uniqKey="Chen X" first="Xin-Xin" last="Chen">Xin-Xin Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Xiao" sort="Wu, Xiao" uniqKey="Wu X" first="Xiao" last="Wu">Xiao Wu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Rui Feng" sort="Chen, Rui Feng" uniqKey="Chen R" first="Rui-Feng" last="Chen">Rui-Feng Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Hai Ming" sort="Jiang, Hai Ming" uniqKey="Jiang H" first="Hai-Ming" last="Jiang">Hai-Ming Jiang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Caiyun" sort="Wang, Caiyun" uniqKey="Wang C" first="Caiyun" last="Wang">Caiyun Wang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020</wicri:regionArea><wicri:noRegion>519020</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Mingrong" sort="Yang, Mingrong" uniqKey="Yang M" first="Mingrong" last="Yang">Mingrong Yang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020</wicri:regionArea><wicri:noRegion>519020</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Jingguang" sort="Lu, Jingguang" uniqKey="Lu J" first="Jingguang" last="Lu">Jingguang Lu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020</wicri:regionArea><wicri:noRegion>519020</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Xiao Dong" sort="Luo, Xiao Dong" uniqKey="Luo X" first="Xiao-Dong" last="Luo">Xiao-Dong Luo</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address: xdluo@mail.kib.ac.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201</wicri:regionArea><wicri:noRegion>650201</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Zhihong" sort="Jiang, Zhihong" uniqKey="Jiang Z" first="Zhihong" last="Jiang">Zhihong Jiang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000</wicri:regionArea><wicri:noRegion>510000</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Zi Feng" sort="Yang, Zi Feng" uniqKey="Yang Z" first="Zi-Feng" last="Yang">Zi-Feng Yang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; KingMed Virology Diagnostic & Translational Center, 510000, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China. Electronic address: jeffyah@163.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; KingMed Virology Diagnostic & Translational Center, 510000, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000</wicri:regionArea><wicri:noRegion>510000</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32702592</idno><idno type="pmid">32702592</idno><idno 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Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; Dongguan People's Hospital, Dongguan, 523000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; Dongguan People's Hospital, Dongguan, 523000</wicri:regionArea><wicri:noRegion>523000</wicri:noRegion></affiliation></author><author><name sortKey="Li, Run Feng" sort="Li, Run Feng" uniqKey="Li R" first="Run-Feng" last="Li">Run-Feng Li</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yi Feng" sort="Wang, Yi Feng" uniqKey="Wang Y" first="Yi-Feng" last="Wang">Yi-Feng Wang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201</wicri:regionArea><wicri:noRegion>650201</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Li Han" sort="Shen, Li Han" uniqKey="Shen L" first="Li-Han" last="Shen">Li-Han Shen</name><affiliation wicri:level="1"><nlm:affiliation>Dongguan People's Hospital, Dongguan, 523000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dongguan People's Hospital, Dongguan, 523000</wicri:regionArea><wicri:noRegion>523000</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Li Hua" sort="Cai, Li Hua" uniqKey="Cai L" first="Li-Hua" last="Cai">Li-Hua Cai</name><affiliation wicri:level="1"><nlm:affiliation>Dongguan People's Hospital, Dongguan, 523000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dongguan People's Hospital, Dongguan, 523000</wicri:regionArea><wicri:noRegion>523000</wicri:noRegion></affiliation></author><author><name sortKey="Weng, Yun Ceng" sort="Weng, Yun Ceng" uniqKey="Weng Y" first="Yun-Ceng" last="Weng">Yun-Ceng Weng</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Huan Rong" sort="Zhang, Huan Rong" uniqKey="Zhang H" first="Huan-Rong" last="Zhang">Huan-Rong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Becton, Dickinson and Company, 510000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Becton, Dickinson and Company, 510000</wicri:regionArea><wicri:noRegion>510000</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xin Xin" sort="Chen, Xin Xin" uniqKey="Chen X" first="Xin-Xin" last="Chen">Xin-Xin Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Xiao" sort="Wu, Xiao" uniqKey="Wu X" first="Xiao" last="Wu">Xiao Wu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Rui Feng" sort="Chen, Rui Feng" uniqKey="Chen R" first="Rui-Feng" last="Chen">Rui-Feng Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Hai Ming" sort="Jiang, Hai Ming" uniqKey="Jiang H" first="Hai-Ming" last="Jiang">Hai-Ming Jiang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Caiyun" sort="Wang, Caiyun" uniqKey="Wang C" first="Caiyun" last="Wang">Caiyun Wang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020</wicri:regionArea><wicri:noRegion>519020</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Mingrong" sort="Yang, Mingrong" uniqKey="Yang M" first="Mingrong" last="Yang">Mingrong Yang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020</wicri:regionArea><wicri:noRegion>519020</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Jingguang" sort="Lu, Jingguang" uniqKey="Lu J" first="Jingguang" last="Lu">Jingguang Lu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020</wicri:regionArea><wicri:noRegion>519020</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Xiao Dong" sort="Luo, Xiao Dong" uniqKey="Luo X" first="Xiao-Dong" last="Luo">Xiao-Dong Luo</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address: xdluo@mail.kib.ac.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201</wicri:regionArea><wicri:noRegion>650201</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Zhihong" sort="Jiang, Zhihong" uniqKey="Jiang Z" first="Zhihong" last="Jiang">Zhihong Jiang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000</wicri:regionArea><wicri:noRegion>510000</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Zi Feng" sort="Yang, Zi Feng" uniqKey="Yang Z" first="Zi-Feng" last="Yang">Zi-Feng Yang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; KingMed Virology Diagnostic & Translational Center, 510000, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China. Electronic address: jeffyah@163.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; KingMed Virology Diagnostic & Translational Center, 510000, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000</wicri:regionArea><wicri:noRegion>510000</wicri:noRegion></affiliation></author></analytic><series><title level="j">Phytomedicine : international journal of phytotherapy and phytopharmacology</title><idno type="eISSN">1618-095X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection.</p></div><div type="abstract" xml:lang="en"><p><b>PURPOSE</b></p><p>To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.</p></div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32702592</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1618-095X</ISSN><JournalIssue CitedMedium="Internet"><Volume>77</Volume><PubDate><Year>2020</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Phytomedicine : international journal of phytotherapy and phytopharmacology</Title><ISOAbbreviation>Phytomedicine</ISOAbbreviation></Journal><ArticleTitle>Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.</ArticleTitle><Pagination><MedlinePgn>153272</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0944-7113(20)30103-3</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.phymed.2020.153272</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection.</AbstractText><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.</AbstractText><CopyrightInformation>Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Hong-Xia</ForeName><Initials>HX</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; Dongguan People's Hospital, Dongguan, 523000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Run-Feng</ForeName><Initials>RF</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yi-Feng</ForeName><Initials>YF</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Li-Han</ForeName><Initials>LH</Initials><AffiliationInfo><Affiliation>Dongguan People's Hospital, Dongguan, 523000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Li-Hua</ForeName><Initials>LH</Initials><AffiliationInfo><Affiliation>Dongguan People's Hospital, Dongguan, 523000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weng</LastName><ForeName>Yun-Ceng</ForeName><Initials>YC</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Huan-Rong</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Becton, Dickinson and Company, 510000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Xin-Xin</ForeName><Initials>XX</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Xiao</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Rui-Feng</ForeName><Initials>RF</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Hai-Ming</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Caiyun</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Mingrong</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Jingguang</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Xiao-Dong</ForeName><Initials>XD</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address: xdluo@mail.kib.ac.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Zhihong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Zi-Feng</ForeName><Initials>ZF</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; KingMed Virology Diagnostic & Translational Center, 510000, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China. Electronic address: jeffyah@163.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>06</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Phytomedicine</MedlineTA><NlmUniqueID>9438794</NlmUniqueID><ISSNLinking>0944-7113</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Acute lung injury</Keyword><Keyword MajorTopicYN="N">Alstonia scholaris</Keyword><Keyword MajorTopicYN="N">Anti-inflammatory</Keyword><Keyword MajorTopicYN="N">Innate immune response</Keyword><Keyword MajorTopicYN="N">Total alkaloids</Keyword><Keyword MajorTopicYN="N">influenza a virus</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest None</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>02</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>06</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>06</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>7</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>7</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32702592</ArticleId><ArticleId IdType="pii">S0944-7113(20)30103-3</ArticleId><ArticleId IdType="doi">10.1016/j.phymed.2020.153272</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhou, Hong Xia" sort="Zhou, Hong Xia" uniqKey="Zhou H" first="Hong-Xia" last="Zhou">Hong-Xia Zhou</name></noRegion><name sortKey="Cai, Li Hua" sort="Cai, Li Hua" uniqKey="Cai L" first="Li-Hua" last="Cai">Li-Hua Cai</name><name sortKey="Chen, Rui Feng" sort="Chen, Rui Feng" uniqKey="Chen R" first="Rui-Feng" last="Chen">Rui-Feng Chen</name><name sortKey="Chen, Xin Xin" sort="Chen, Xin Xin" uniqKey="Chen X" first="Xin-Xin" last="Chen">Xin-Xin Chen</name><name sortKey="Jiang, Hai Ming" sort="Jiang, Hai Ming" uniqKey="Jiang H" first="Hai-Ming" last="Jiang">Hai-Ming Jiang</name><name sortKey="Jiang, Zhihong" sort="Jiang, Zhihong" uniqKey="Jiang Z" first="Zhihong" last="Jiang">Zhihong Jiang</name><name sortKey="Li, Run Feng" sort="Li, Run Feng" uniqKey="Li R" first="Run-Feng" last="Li">Run-Feng Li</name><name sortKey="Lu, Jingguang" sort="Lu, Jingguang" uniqKey="Lu J" first="Jingguang" last="Lu">Jingguang Lu</name><name sortKey="Luo, Xiao Dong" sort="Luo, Xiao Dong" uniqKey="Luo X" first="Xiao-Dong" last="Luo">Xiao-Dong Luo</name><name sortKey="Shen, Li Han" sort="Shen, Li Han" uniqKey="Shen L" first="Li-Han" last="Shen">Li-Han Shen</name><name sortKey="Wang, Caiyun" sort="Wang, Caiyun" uniqKey="Wang C" first="Caiyun" last="Wang">Caiyun Wang</name><name sortKey="Wang, Yi Feng" sort="Wang, Yi Feng" uniqKey="Wang Y" first="Yi-Feng" last="Wang">Yi-Feng Wang</name><name sortKey="Weng, Yun Ceng" sort="Weng, Yun Ceng" uniqKey="Weng Y" first="Yun-Ceng" last="Weng">Yun-Ceng Weng</name><name sortKey="Wu, Xiao" sort="Wu, Xiao" uniqKey="Wu X" first="Xiao" last="Wu">Xiao Wu</name><name sortKey="Yang, Mingrong" sort="Yang, Mingrong" uniqKey="Yang M" first="Mingrong" last="Yang">Mingrong Yang</name><name sortKey="Yang, Zi Feng" sort="Yang, Zi Feng" uniqKey="Yang Z" first="Zi-Feng" last="Yang">Zi-Feng Yang</name><name sortKey="Zhang, Huan Rong" sort="Zhang, Huan Rong" uniqKey="Zhang H" first="Huan-Rong" last="Zhang">Huan-Rong Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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