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10.1177/24725552211019405

http://scihub22266oqcxt.onion/10.1177/24725552211019405
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34078171!8458684!34078171
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suck abstract from ncbi


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pmid34078171      SLAS+Discov 2021 ; 26 (9): 1091-1106
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  • Application of a High-Content Screening Assay Utilizing Primary Human Lung Fibroblasts to Identify Antifibrotic Drugs for Rapid Repurposing in COVID-19 Patients #MMPMID34078171
  • Marwick JA; Elliott RJR; Longden J; Makda A; Hirani N; Dhaliwal K; Dawson JC; Carragher NO
  • SLAS Discov 2021[Oct]; 26 (9): 1091-1106 PMID34078171show ga
  • Lung imaging and autopsy reports among COVID-19 patients show elevated lung scarring (fibrosis). Early data from COVID-19 patients as well as previous studies from severe acute respiratory syndrome, Middle East respiratory syndrome, and other respiratory disorders show that the extent of lung fibrosis is associated with a higher mortality, prolonged ventilator dependence, and poorer long-term health prognosis. Current treatments to halt or reverse lung fibrosis are limited; thus, the rapid development of effective antifibrotic therapies is a major global medical need that will continue far beyond the current COVID-19 pandemic. Reproducible fibrosis screening assays with high signal-to-noise ratios and disease-relevant readouts such as extracellular matrix (ECM) deposition (the hallmark of fibrosis) are integral to any antifibrotic therapeutic development. Therefore, we have established an automated high-throughput and high-content primary screening assay measuring transforming growth factor-beta (TGFbeta)-induced ECM deposition from primary human lung fibroblasts in a 384-well format. This assay combines longitudinal live cell imaging with multiparametric high-content analysis of ECM deposition. Using this assay, we have screened a library of 2743 small molecules representing approved drugs and late-stage clinical candidates. Confirmed hits were subsequently profiled through a suite of secondary lung fibroblast phenotypic screening assays quantifying cell differentiation, proliferation, migration, and apoptosis. In silico target prediction and pathway network analysis were applied to the confirmed hits. We anticipate this suite of assays and data analysis tools will aid the identification of new treatments to mitigate against lung fibrosis associated with COVID-19 and other fibrotic diseases.
  • |*COVID-19 Drug Treatment[MESH]
  • |*Drug Discovery[MESH]
  • |Apoptosis/drug effects[MESH]
  • |COVID-19/epidemiology/virology[MESH]
  • |Cell Differentiation/drug effects[MESH]
  • |Cell Movement/drug effects[MESH]
  • |Cell Proliferation/drug effects[MESH]
  • |Extracellular Matrix/drug effects/pathology[MESH]
  • |Fibroblasts/drug effects[MESH]
  • |Humans[MESH]
  • |Lung/*diagnostic imaging/drug effects/pathology/virology[MESH]
  • |Mass Screening[MESH]
  • |Pandemics[MESH]
  • |SARS-CoV-2/pathogenicity[MESH]
  • |Signal Transduction/drug effects[MESH]


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