Evidence map›Paper›PMID 33806560›Full record

ArticleInternational journal of molecular sciences2021

Small Immunomodulatory Molecules as Potential Therapeutics in Experimental Murine Models of Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS).

Dilip Shah, Pragnya Das, Suchismita Acharya, Beamon Agarwal, Dale J Christensen, Stella M Robertson, Vineet Bhandari

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

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  12. Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
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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

7 authors.

Dilip ShahDivision of Neonatology, Department of Pediatrics, Drexel University, Philadelphia, PA 19197, USA.
Pragnya DasDivision of Neonatology, Department of Pediatrics, Drexel University, Philadelphia, PA 19197, USA.ORCID 0000-0003-4818-2387
Suchismita AcharyaAyuVis Research, Inc., 1120 South Freeway, Fort Worth, TX 76104, USA.
Beamon AgarwalGenomeRxUS, Secane, PA 19018, USA.
Dale J ChristensenDale J. Christensen Consulting LLC, Cary, NC 27511, USA.
Stella M RobertsonAyuVis Research, Inc., 1120 South Freeway, Fort Worth, TX 76104, USA.ORCID 0000-0002-9349-9781
Vineet BhandariDivision of Neonatology, Department of Pediatrics, Drexel University, Philadelphia, PA 19197, USA.ORCID 0000-0002-4900-6636

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
AyuVis Research Sponsored ContractNCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

backgroundAcute lung injury (ALI) or its most advanced form, acute respiratory distress syndrome (ARDS) is a severe inflammatory pulmonary process triggered by a variety of insults including sepsis, viral or bacterial pneumonia, and mechanical ventilator-induced trauma. Currently, there are no effective therapies available for ARDS. We have recently reported that a novel small molecule AVR-25 derived from chitin molecule (a long-chain polymer of N-acetylglucosamine) showed anti-inflammatory effects in the lungs. The goal of this study was to determine the efficacy of two chitin-derived compounds, AVR-25 and AVR-48, in multiple mouse models of ALI/ARDS. We further determined the safety and pharmacokinetic (PK) profile of the lead compound AVR-48 in rats.

methodsALI in mice was induced by intratracheal instillation of a single dose of lipopolysaccharide (LPS; 100 µg) for 24 h or exposed to hyperoxia (100% oxygen) for 48 h or undergoing cecal ligation and puncture (CLP) procedure and observation for 10 days.

resultsBoth chitin derivatives, AVR-25 and AVR-48, showed decreased neutrophil recruitment and reduced inflammation in the lungs of ALI mice. Further, AVR-25 and AVR-48 mediated diminished lung inflammation was associated with reduced expression of lung adhesion molecules with improvement in pulmonary endothelial barrier function, pulmonary edema, and lung injury. Consistent with these results, CLP-induced sepsis mice treated with AVR-48 showed a significant increase in survival of the mice (80%) and improved lung histopathology in the treated CLP group. AVR-48, the lead chitin derivative compound, demonstrated a good safety profile.

conclusionBoth AVR-25 and AVR-48 demonstrate the potential to be developed as therapeutic agents to treat ALI/ARDS.

Indexed as

Acute Lung InjuryAnimalsChitinDisease Models, AnimalFemaleImmunologic FactorsLipopolysaccharidesLungMaleMiceMice, Inbred C57BLPneumoniaPulmonary EdemaRatsRats, Sprague-DawleyRespiratory Distress SyndromeAVR-25ChitinImmunologic FactorsLipopolysaccharidesSmall Molecule Librariesacute lung injuryAVR-25AVR-48lung inflammationpulmonary edemasepsis

Identifiers

PMID33806560
PMCPMC7961996

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Registered trials

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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.