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Stefano","nameType":"Personal","givenName":"Stefano","familyName":"Guido","affiliation":[],"nameIdentifiers":[]},{"name":"Bossi, Anna","nameType":"Personal","givenName":"Anna","familyName":"Bossi","affiliation":[],"nameIdentifiers":[]},{"name":"Zolin, Anna","nameType":"Personal","givenName":"Anna","familyName":"Zolin","affiliation":[],"nameIdentifiers":[]},{"name":"Venerando, Andrea","nameType":"Personal","givenName":"Andrea","familyName":"Venerando","affiliation":[],"nameIdentifiers":[]},{"name":"Pinna, Lorenzo A","nameType":"Personal","givenName":"Lorenzo A","familyName":"Pinna","affiliation":[],"nameIdentifiers":[]},{"name":"Mehta, Anil","nameType":"Personal","givenName":"Anil","familyName":"Mehta","affiliation":[],"nameIdentifiers":[]},{"name":"Bona, Gianni","nameType":"Personal","givenName":"Gianni","familyName":"Bona","affiliation":[],"nameIdentifiers":[]},{"name":"Kroemer, 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sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Physiology"},{"subject":"Genetics"},{"subject":"Cell Biology"},{"subject":"Medicine"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-01-29","dateType":"Created"},{"date":"2016-01-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.4161/15548627.2014.973737","relatedIdentifierType":"DOI"},{"relationType":"IsPreviousVersionOf","relatedIdentifier":"10.6084/m9.figshare.1247659","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["227852 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in \u003ci\u003eCftr\u003csup\u003eF508del\u003c/sup\u003e\u003c/i\u003e homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the \u003ci\u003eF508del-CFTR\u003c/i\u003e mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from \u003ci\u003eF508del\u003c/i\u003e homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both \u003ci\u003ein vivo\u003c/i\u003e, in mice, and \u003ci\u003ein vitro\u003c/i\u003e, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 \u003ci\u003eF508del-CFTR\u003c/i\u003e homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells \u003ci\u003ein vivo\u003c/i\u003e, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of \u003ci\u003eTNF/TNF-alpha (tumor necrosis factor)\u003c/i\u003e and \u003ci\u003eCXCL8\u003c/i\u003e (\u003ci\u003echemokine [C-X-C motif] ligand 8\u003c/i\u003e) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the \u003ci\u003eF508del-CFTR\u003c/i\u003e mutation.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjEvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLjEyNDc2NTkuVjI8L2lkZW50aWZpZXI+CiAgPGNyZWF0b3JzPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5EYW5pZWxhIERlIFN0ZWZhbm88L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5WYWxlcmlhIFIgVmlsbGVsbGE8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5TcGVyYW56YSBFc3Bvc2l0bzwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkFudG9uZWxsYSBUb3NjbzwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkFuZ2VsYSBTZXBlPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+RmFiaW9sYSBEZSBHcmVnb3JpbzwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkxhdXJhIFNhbHZhZG9yaTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlJvc2EgR3Jhc3NpYTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkNhcmxvIEEgTGVvbmU8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5HaXVzZXBwZSBEZSBSb3NhPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+TWFyaWEgQyBNYWl1cmk8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5NYXNzaW1vIFBldHRvZWxsby1NYW50b3Zhbmk8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5TdGVmYW5vIEd1aWRvPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+QW5uYSBCb3NzaTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkFubmEgWm9saW48L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5BbmRyZWEgVmVuZXJhbmRvPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+TG9yZW56byBBIFBpbm5hPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+QW5pbCBNZWh0YTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkdpYW5uaSBCb25hPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+R3VpZG8gS3JvZW1lcjwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkx1aWdpIE1haXVyaTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlZhbGVyaWEgUmFpYTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgPC9jcmVhdG9ycz4KICA8dGl0bGVzPgogICAgPHRpdGxlPlJlc3RvcmF0aW9uIG9mIENGVFIgZnVuY3Rpb24gaW4gcGF0aWVudHMgd2l0aCBjeXN0aWMgZmlicm9zaXMgY2FycnlpbmcgdGhlIEY1MDhkZWwtQ0ZUUiBtdXRhdGlvbjwvdGl0bGU+CiAgPC90aXRsZXM+CiAgPGRlc2NyaXB0aW9ucz4KICAgIDxkZXNjcmlwdGlvbiBkZXNjcmlwdGlvblR5cGU9IkFic3RyYWN0Ij4mbHQ7ZGl2Jmd0OyZsdDtwJmd0O1Jlc3RvcmF0aW9uIG9mIEJFQ04xL0JlY2xpbiAxLWRlcGVuZGVudCBhdXRvcGhhZ3kgYW5kIGRlcGxldGlvbiBvZiBTUVNUTTEvcDYyIGJ5IGdlbmV0aWMgbWFuaXB1bGF0aW9uIG9yIGF1dG9waGFneS1zdGltdWxhdG9yeSBwcm90ZW9zdGFzaXMgcmVndWxhdG9ycywgc3VjaCBhcyBjeXN0YW1pbmUsIGhhdmUgcG9zaXRpdmUgZWZmZWN0cyBvbiBtb3VzZSBtb2RlbHMgb2YgaHVtYW4gY3lzdGljIGZpYnJvc2lzIChDRikuIFRoZXNlIG1lYXN1cmVzIHJlc2N1ZSB0aGUgZnVuY3Rpb25hbCBleHByZXNzaW9uIG9mIHRoZSBtb3N0IGZyZXF1ZW50IHBhdGhvZ2VuaWMgQ0ZUUiBtdXRhbnQsIEY1MDhkZWwsIGF0IHRoZSByZXNwaXJhdG9yeSBlcGl0aGVsaWFsIHN1cmZhY2UgYW5kIHJlZHVjZSBsdW5nIGluZmxhbW1hdGlvbiBpbiAmbHQ7aSZndDtDZnRyJmx0O3N1cCZndDtGNTA4ZGVsJmx0Oy9zdXAmZ3Q7Jmx0Oy9pJmd0OyBob21venlnb3VzIG1pY2UuIEN5c3RlYW1pbmUsIHRoZSByZWR1Y2VkIGZvcm0gb2YgY3lzdGFtaW5lLCBpcyBhbiBGREEtYXBwcm92ZWQgZHJ1Zy4gSGVyZSwgd2UgcmVwb3J0IHRoYXQgb3JhbCB0cmVhdG1lbnQgd2l0aCBjeXN0ZWFtaW5lIGdyZWF0bHkgcmVkdWNlcyB0aGUgbW9ydGFsaXR5IHJhdGUgYW5kIGltcHJvdmVzIHRoZSBwaGVub3R5cGUgb2YgbmV3Ym9ybiBtaWNlIGJlYXJpbmcgdGhlICZsdDtpJmd0O0Y1MDhkZWwtQ0ZUUiZsdDsvaSZndDsgbXV0YXRpb24uIEN5c3RlYW1pbmUgd2FzIGFsc28gYWJsZSB0byBpbmNyZWFzZSB0aGUgcGxhc21hIG1lbWJyYW5lIGV4cHJlc3Npb24gb2YgdGhlIEY1MDhkZWwtQ0ZUUiBwcm90ZWluIGluIG5hc2FsIGVwaXRoZWxpYWwgY2VsbHMgZnJvbSAmbHQ7aSZndDtGNTA4ZGVsJmx0Oy9pJmd0OyBob21venlnb3VzIENGIHBhdGllbnRzLCBhbmQgdGhlc2UgZWZmZWN0cyBwZXJzaXN0ZWQgZm9yIDI0wqBoIGFmdGVyIGN5c3RlYW1pbmUgd2l0aGRyYXdhbC4gSW1wb3J0YW50bHksIHRoaXMgY3lzdGVhbWluZSBlZmZlY3QgYWZ0ZXIgd2FzaG91dCB3YXMgZnVydGhlciBzdXN0YWluZWQgYnkgdGhlIHNlcXVlbnRpYWwgYWRtaW5pc3RyYXRpb24gb2YgZXBpZ2FsbG9jYXRlY2hpbiBnYWxsYXRlIChFR0NHKSwgYSBncmVlbiB0ZWEgZmxhdm9ub2lkLCBib3RoICZsdDtpJmd0O2luIHZpdm8mbHQ7L2kmZ3Q7LCBpbiBtaWNlLCBhbmQgJmx0O2kmZ3Q7aW4gdml0cm8mbHQ7L2kmZ3Q7LCBpbiBwcmltYXJ5IGVwaXRoZWxpYWwgY2VsbHMgZnJvbSBDRiBwYXRpZW50cy4gSW4gYSBwaWxvdCBjbGluaWNhbCB0cmlhbCBpbnZvbHZpbmcgMTAgJmx0O2kmZ3Q7RjUwOGRlbC1DRlRSJmx0Oy9pJmd0OyBob21venlnb3VzIENGIHBhdGllbnRzLCB0aGUgY29tYmluYXRpb24gb2YgY3lzdGVhbWluZSBhbm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