Evidence map›Paper›PMID 36303116›Full record

ArticleMolecular medicine (Cambridge, Mass.)2022

Inhibition of platelet activation suppresses reactive enteric glia and mitigates intestinal barrier dysfunction during sepsis.

Bo Cheng, Mengyu Du, Shuxuan He, Lan Yang, Xi Wang, Hui Gao, Haiqing Chang, Wei Gao, Yan Li, Qiang Wang and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Bo Cheng *Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Mengyu Du *Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Shuxuan HeDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Lan YangDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Xi WangDepartment of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Hui GaoDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Haiqing ChangDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Wei GaoDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Yan LiDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Qiang WangDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.ORCID http://orcid.org/0000-0002-3637-2063
Yansong LiDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. liyansong.inter@163.com.ORCID http://orcid.org/0000-0003-4949-0576
First Affiliated Hospital of Xi'an Jiaotong University · CNWenzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntestinal barrier dysfunction, which is associated with reactive enteric glia cells (EGCs), is not only a result of early sepsis but also a cause of multiple organ dysfunction syndrome. Inhibition of platelet activation has been proposed as a potential treatment for septic patients because of its efficacy in ameliorating the organ damage and barrier dysfunction. During platelet activation, CD40L is translocated from α granules to the platelet surface, serving as a biomarker of platelet activation a reliable predictor of sepsis prognosis. Given that more than 95% of the circulating CD40L originate from activated platelets, the present study aimed to investigate if inhibiting platelet activation mitigates intestinal barrier dysfunction is associated with suppressing reactive EGCs and its underlying mechanism.

methodsCecal ligation and puncture (CLP) was performed to establish the sepsis model. 24 h after CLP, the proportion of activated platelets, the level of sCD40L, the expression of tight-junction proteins, the intestinal barrier function and histological damage of septic mice were analyzed. In vitro, primary cultured EGCs were stimulated by CD40L and LPS for 24 h and EGCs-conditioned medium were collected for Caco-2 cells treatment. The expression of tight-junction proteins and transepithelial electrical resistance of Caco-2 cell were evaluated.

resultsIn vivo, inhibiting platelet activation with cilostazol mitigated the intestinal barrier dysfunction, increased the expression of ZO-1 and occludin and improved the survival rate of septic mice. The efficacy was associated with reduced CD40L

conclusionsThe inhibition of platelet activation is related to the suppression of CD40L-CD40-TRAF6 signaling pathway and the reduction of EGCs activation, which promotes intestinal barrier function and survival in sepsis mice. These results might provide a potential therapeutic strategy and a promising target for sepsis.

Indexed as

CD40 LigandSepsisAnimalsCaco-2 CellsCulture Media, ConditionedHumansMiceNeurogliaOccludinPlatelet ActivationRNA, Small InterferingS-NitrosoglutathioneTight Junction ProteinsTNF Receptor-Associated Factor 6CD40 LigandCulture Media, ConditionedOccludinRNA, Small InterferingS-NitrosoglutathioneTight Junction ProteinsTNF Receptor-Associated Factor 6CD40L–CD40Enteric glia cellsIntestinal barrier dysfunctionSepsisS-nitrosoglutathione

Identifiers

PMID36303116
PMCPMC9615156
OpenAlexW4307439752

What OpenQuestion holds

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LicenceCC BY
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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.