Evidence map›Paper›PMID 31747882›Full record

ArticleMolecular medicine (Cambridge, Mass.)2019

Recombinant human milk fat globule-EGF factor VIII (rhMFG-E8) as a therapy for sepsis after acute exposure to alcohol.

Wayne W Chaung, Max Brenner, Hao-Ting Yen, Mahendar L Ochani, Asha Jacob, Ping Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Wayne W ChaungTheraSource LLC, 350 Community Dr, Manhasset, NY, 11030, USA. wayne_chaung@therasourcellc.com.ORCID 0000-0002-1646-3814
Max BrennerTheraSource LLC, 350 Community Dr, Manhasset, NY, 11030, USA.
Hao-Ting YenTheraSource LLC, 350 Community Dr, Manhasset, NY, 11030, USA.
Mahendar L OchaniTheraSource LLC, 350 Community Dr, Manhasset, NY, 11030, USA.
Asha JacobCenter for Immunology and Inflammation, The Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.
Ping WangCenter for Immunology and Inflammation, The Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA. pwang@northwell.edu.
Feinstein Institute for Medical Research · USTheraSource (United States) · US

Funding

Human Ghrelin as an Effective Mitigator of Acute Radiation InjuryR44AI096777 · NIAID · THERASOURCE, LLC · PI YANG, WENG-LANG · 2016 to 2018
$3.0M
A Novel Therapy for Septic ShockR44HL091602 · NHLBI · THERASOURCE, LLC · PI QIANG, XIAOLING · 2008 to 2011
$2.0M
NHLBI NIH HHS R44 HL091602NIAAA NIH HHS HHSN275201300007CNIAID NIH HHS R44 AI096777NICHD NIH HHS HHSN275201200002CNICHD NIH HHS HHSN275201200002INICHD NIH HHS HHSN275201300007C
6 · The paper itself

Abstract

backgroundAlcohol intake predisposes to infections and sepsis. Alcohol and sepsis inhibit the expression of milk fat globule epidermal growth factor-factor VIII (MFG-E8), a glycoprotein essential for optimal efferocytosis, resulting in the release of proinflammatory molecules and increased sepsis severity. We previously reported that recombinant mouse (rm) MFG-E8 attenuates sepsis-induced organ injury in rats with acute alcohol intoxication. In order to develop a therapy that can be safely used in humans, we have produced recombinant human (rh) MFG-E8 and evaluated its efficacy to ameliorate sepsis after acute exposure to alcohol.

methodsWe induced acute alcohol intoxication with a bolus injection of alcohol (1.75 g/kg BW) followed by an intravenous infusion of 300 mg/kg/h alcohol for 10 h. Sepsis was then induced by cecal ligation and puncture (CLP). At -10, 0, and 10 h relative to CLP, rats received MFG-E8 or vehicle (albumin) intravenously. Animals were euthanized at 20 h after CLP for blood and tissue collection. Additional groups of animals were used for a survival study.

resultsCompared to vehicle, rhMFG-E8 treatment ameliorated blood levels of proinflammatory cytokines (% improvement: TNF-α 49.8%, IL-6 34.7%) and endotoxin (61.7%), as well as of transaminases (AST 36.2%, ALT 40.1%) and lactate (18.4%). Rats treated with rhMFG-E8 also had a significant histological attenuation of the acute lung injury, as well as a reduction in the number of apoptotic cells in the thymus (43.4%) and cleaved caspase 3 (38.7%) in the spleen. In addition, rhMFG-E8 improved the 10-day sepsis survival rate from 45 to 80%

conclusionrhMFG-E8 significantly ameliorated sepsis in rats with acute alcohol exposure, demonstrating rhMFG-E8's potential to be developed as an effective therapy for sepsis in alcohol abusers.

Indexed as

SepsisAcute Lung InjuryAlcoholsAnimalsAntigens, SurfaceApoptosisChemical and Drug Induced Liver InjuryCytokinesDisease Models, AnimalLiverLungMaleMilk ProteinsRatsRats, Sprague-DawleyRecombinant ProteinsAlcoholsAntigens, SurfaceCytokinesMFGE8 protein, humanMilk ProteinsRecombinant ProteinsAlcoholCLPrhMFG-E8SepsisSurvivalTherapy

Identifiers

PMID31747882
PMCPMC6868720
OpenAlexW2989751554

What OpenQuestion holds

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LicenceCC BY
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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.