Evidence map›Paper›PMID 30282819›Full record

ArticleJCI insight2018

Ex vivo lung perfusion as a human platform for preclinical small molecule testing.

Nathaniel M Weathington, Diana Álvarez, John Sembrat, Josiah Radder, Nayra Cárdenes, Kentaro Noda, Qiaoke Gong, Hesper Wong, Jay Kolls, Jonathan D'Cunha and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Review
  3. Label-free viability assessment ofBiomedical optics express · 2026
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  5. Frontiers in immunology · 2025
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  11. Pushing the boundaries of innovation: the potential ofFrontiers in cardiovascular medicine · 2023
    Review
  12. Article
  13. Article
  14. Ex-vivo lung perfusion therapies: do they add value to organ donation?Current opinion in organ transplantation · 2022
    Review
  15. Human Lung-Resident Macrophages Colocalize with and Provide Costimulation to PD1American journal of respiratory and critical care medicine · 2021
    Article
  16. Review
  17. Article
  18. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Nathaniel M WeathingtonDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Diana ÁlvarezDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
John SembratDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Josiah RadderDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Nayra CárdenesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Kentaro NodaDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Qiaoke GongDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Hesper WongDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Jay KollsDepartment of Medicine, Tulane University, New Orleans, Louisiana.
Jonathan D'CunhaDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Rama K MallampalliDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Bill B ChenDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Mauricio RojasDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Pulmonary and Allergy Associates · USUniversity of Pittsburgh · USTulane University · US

Funding

Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2014 to 2023
$21.3M
Translational studies for identifying and targeting novel pathways in systemic sclerosis pathogenesisP50AR060780 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LAFYATIS, ROBERT A. · 2011 to 2021
$14.9M
Systematic Investigation of Protein Ubiquitination in ARDSR35HL139860 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, BEIBEI · 2018 to 2024
$6.3M
TNF-alpha Control of a Surfactant Enzyme in Lung InjuryR01HL081784 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2006 to 2024
$5.4M
F box-Induced Acute Lung Injury and ParkinR01HL096376 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2010 to 2025
$5.1M
Sepsis-Associated Immune Suppression and F-box ProteinsR01HL097376 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2009 to 2025
$5.1M
Stabilizing mitochondria in sepsisR01HL098174 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2010 to 2021
$3.6M
A New Genus of Ubiquitin-Based Anti-inflammatories for COPDUH2HL123502 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2015
$3.0M
Role of F-Box Proteins in Lung TransplantationR01HL133184 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, BEIBEI, MCDYER, JOHN F · 2017 to 2020
$2.1M
Aging of Mesenchymal Stem Cells Missing Link in IPFR01HL123766 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROJAS, MAURICIO · 2015 to 2018
$1.9M
Cellular regulation of the IL-22 receptor and its importance in lung immunity.K08HL126135 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WEATHINGTON, NATHANIEL M · 2015 to 2019
$766k
NHLBI NIH HHS K08 HL126135NHLBI NIH HHS P01 HL114453NHLBI NIH HHS R01 HL081784NHLBI NIH HHS R01 HL096376NHLBI NIH HHS R01 HL097376NHLBI NIH HHS R01 HL098174NHLBI NIH HHS R01 HL123766NHLBI NIH HHS R01 HL133184NHLBI NIH HHS R35 HL139860NHLBI NIH HHS UH2 HL123502NIAMS NIH HHS P50 AR060780
6 · The paper itself

Abstract

The acute respiratory distress syndrome (ARDS) causes an estimated 70,000 US deaths annually. Multiple pharmacologic interventions for ARDS have been tested and failed. An unmet need is a suitable laboratory human model to predictively assess emerging therapeutics on organ function in ARDS. We previously demonstrated that the small molecule BC1215 blocks actions of a proinflammatory E3 ligase-associated protein, FBXO3, to suppress NF-κB signaling in animal models of lung injury. Ex vivo lung perfusion (EVLP) is a clinical technique that maintains lung function for possible transplant after organ donation. We used human lungs unacceptable for transplant to model endotoxemic injury with EVLP for 6 hours. LPS infusion induced inflammatory injury with impaired oxygenation of pulmonary venous circulation. BC1215 treatment after LPS rescued oxygenation and decreased inflammatory cytokines in bronchoalveolar lavage. RNA sequencing transcriptomics from biopsies taken during EVLP revealed robust inflammatory gene induction by LPS with a strong signal for NF-κB-associated transcripts. BC1215 treatment reduced the LPS induction of genes associated with inflammatory and host defense gene responses by Gene Ontology (GOterm) and pathways analysis. BC1215 also significantly antagonized LPS-mediated NF-κB activity. EVLP may provide a unique human platform for preclinical study of chemical entities such as FBXO3 inhibitors on tissue physiology.

Indexed as

AdolescentAdultBenzylaminesDrug Evaluation, PreclinicalF-Box ProteinsFemaleHumansLipopolysaccharidesLungMaleMiddle AgedPerfusionPyridinesRespiratory Distress SyndromeSignal TransductionBC-1215BenzylaminesF-Box ProteinsFBXO3 protein, humanLipopolysaccharidesPyridinesInflammationInnate immunityNF-kappaBPulmonologyToxins/drugs/xenobiotics

Identifiers

PMID30282819
PMCPMC6237445
OpenAlexW2894618881

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.