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PBI-compound, a novel first-in-class anti-fibrotic compound, reduces lung fibrosis in the bleomycin-induced lung fibrosis model: A comparative study with pirfenidone

2013· article· en· W1547482497 on OpenAlexaff
Lyne Gagnon, Mikaël Tremblay, François Sarra‐Bournet, Liette Gervais, Shaun Abbott, Jean‐Simon Duceppe, Boulos Zacharie, Christopher Penney, Pierre Laurin, Brigitte Grouix

Bibliographic record

VenueEuropean Respiratory Journal · 2013
Typearticle
Languageen
FieldMedicine
TopicInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Canadian institutionsAptose Biosciences (Canada)
Fundersnot available
KeywordsPirfenidoneCTGFBleomycinMedicineIdiopathic pulmonary fibrosisPulmonary fibrosisFibrosisLungCombination therapyFibronectinInflammationPharmacologyCancer researchInternal medicineExtracellular matrixChemotherapyGrowth factorBiochemistryChemistryReceptor

Abstract

fetched live from OpenAlex

Background : The pathobiological mechanisms underlying the development of idiopathic pulmonary fibrosis (IPF) are highly complex. Aims : To compare the effect of PBI-Compound, pirfenidone, and combination of both compounds on inflammatory/fibrotic mRNA expression of key mediators (inflammation/pro-fibrotic: TGF-β, CTGF, IL 6, IL23p19; fibrotic: collagen I, fibronectin; and remodeling: SPARC, MMP-2), and on histological lesions in the bleomycin-induced lung fibrosis model. Methods : Intratracheal instillation of bleomycin was administered on day 0. Mice were treated with PBI-Compound, or pirfenidone, or combination of both compounds starting on day 7 to 21. Results : Bleomycin induced a significant increase in mRNA expression of all key mediators in the lung. PBI-Compound and combination therapy significantly decreased TGF-β, CTGF, IL-6 and IL23p19 expression in lung, while pirfenidone had no effect on CTGF. All treatments induced a significant reduction of collagen I and fibronectin expression to the control level (no bleomycin). PBI-Compound and combination therapy induced a significant reduction of SPARC while pirfenidone demonstrated no effect. PBI-Compound and pirfenidone induced a weak inhibition of MMP-2 while the combination therapy induced a significant reduction. Based on Ashcroft’s score, PBI-Compound and combination therapy demonstrated significant reduction of lung fibrosis while pirfenidone alone demonstrated weak but no significant activity at the histological level. Conclusions : PBI-Compound or combination therapy with pirfenidone may be an efficacious treatment in IPF.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.037
GPT teacher head0.284
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2013
Admission routes1
Has abstractyes

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