https://scholars.lib.ntu.edu.tw/handle/123456789/523439
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Lai W.-Y. | en_US |
dc.contributor.author | Wang J.-W. | en_US |
dc.contributor.author | Huang B.-T. | en_US |
dc.contributor.author | Lin E.P.-Y. | en_US |
dc.contributor.author | PAN-CHYR YANG | en_US |
dc.creator | Lai W.-Y.;Wang J.-W.;Huang B.-T.;Lin E.P.-Y.;Pan-Chyr Yang | - |
dc.date.accessioned | 2020-12-02T02:33:10Z | - |
dc.date.available | 2020-12-02T02:33:10Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065481293&doi=10.7150%2fthno.30972&partnerID=40&md5=a884985c996387130145cb8d48640681 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/523439 | - |
dc.description.abstract | Rationale: The TNF-α pathway plays as a double-edged sword that simultaneously regulates cell apoptosis and proliferation. The dysregulated TNF-α signaling can trigger cytokine storms that lead to profound cell death during the phase of acute tissue injury. On the other hand, an optimal level of TNF-α signaling is required for tissue repair following the acute injury phase. The TNF-α pathway is commonly upregulated in acute lung injury (ALI) and acute liver failure (ALF). Previous studies investigated the feasibility of adopting protein-based TNF-α blockers as disease modifiers in ALI and ALF, but none of these came out with a positive result. One of the potential reasons that resides behind the failure of the trials might be the long half-life of these inhibitors that led to undesired side effects. Developing alternative TNF-α blockers with manageable half-lives remain an unmet need in this regard. Methods: In the current study, we developed a novel TNF-α-targeting aptamer (aptTNF-α) and its PEG-derivate (aptTNF-α-PEG) with antagonistic functions. We investigated the in vivo antagonistic effects using mouse ALI and ALF models. Results: Our data showed that aptTNF-α possessed good in vitro binding affinity towards human/mouse TNF-α and successfully targeted TNF-α in vivo. In the mouse ALI model, aptTNF-α/aptTNF-α-PEG treatment attenuated the severity of LPS-induced ALI, as indicated by the improvement of oxygen saturation and lung injury scores, the reduction of protein-rich fluid leakage and neutrophil infiltration in the alveolar spaces, and the suppression of pro-inflammatory cytokines/chemokines expressions in the lung tissues. In the mouse ALF model, we further showed that aptTNF-α/aptTNF-α-PEG treatment not only attenuated the degree of hepatocyte damage upon acute injury but also potentiated early regeneration of the liver tissues. Conclusion: The results implicated potential roles of aptTNF-α/aptTNF-α-PEG in ALI and ALF. The data also suggested their translational potential as a new category of TNF-α blocking agent. ? Ivyspring International Publisher. | - |
dc.publisher | Ivyspring International Publisher | - |
dc.relation.ispartof | Theranostics | - |
dc.subject | Acute liver failure; Acute lung injury; Aptamer; TNF-α | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | aptamer; chemokine; cytokine; oxygen; tumor necrosis factor inhibitor; antiinflammatory agent; aptamer; tumor necrosis factor; acute liver failure; acute lung injury; animal cell; animal experiment; animal model; animal tissue; Article; binding affinity; controlled study; disease severity; human; in vitro study; in vivo study; liver cell damage; liver regeneration; lung parenchyma; mouse; neutrophil chemotaxis; nonhuman; oxygen saturation; protein expression; protein targeting; respiratory tract disease assessment; scoring system; acute liver failure; acute lung injury; animal; disease model; isolation and purification; molecularly targeted therapy; pathology; procedures; treatment outcome; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Aptamers, Nucleotide; Disease Models, Animal; Humans; Liver Failure, Acute; Mice; Molecular Targeted Therapy; Treatment Outcome; Tumor Necrosis Factor-alpha | - |
dc.title | A novel TNF-α-targeting aptamer for TNF-α-mediated acute lung injury and acute liver failure | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.7150/thno.30972 | - |
dc.identifier.pmid | 31037135 | - |
dc.identifier.scopus | 2-s2.0-85065481293 | - |
dc.relation.pages | 1741-1751 | - |
dc.relation.journalvolume | 9 | - |
dc.relation.journalissue | 6 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Internal Medicine | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Clinical Pharmacy | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Biomedical Electronics and Bioinformatics | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.orcid | 0000-0001-6330-6048 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Electrical Engineering and Computer Science | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學系 |
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