Evidence map›Paper›PMID 31393259›Full record

ArticleMicroRNA (Shariqah, United Arab Emirates)2020

Granzyme B and miR-378a Interaction in Acetaminophen Toxicity in Children.

Sandra McCullough, Harsh Dweep, Mitchell R McGill, Sudeepa Bhattacharyya, Laura James, Sara Frankowski, Aaron Woodall, Gregory Kearns, Pritmohinder Gill

Open access · greenAbstract read
In one paragraph

Article in MicroRNA (Shariqah, United Arab Emirates), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 90% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

9 authors at 3 institutions in 1 country.

Sandra McCulloughDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
Harsh DweepThe Wistar Institute, 3601 Spruce St, Philadelphia, PA, 19104, United States.
Mitchell R McGillDepartment of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Sudeepa BhattacharyyaDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
Laura JamesDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
Sara FrankowskiArkansas Children's Research Institute, Little Rock, AR 72202, United States.
Aaron WoodallArkansas Children's Research Institute, Little Rock, AR 72202, United States.
Gregory KearnsDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
Pritmohinder GillDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
Arkansas Children's Hospital · USThe Wistar Institute · USUniversity of Arkansas for Medical Sciences · US

Funding

Adduct Dipstick for Diagnosis of Acetaminophen ToxicityR42DK079387 · NIDDK · ACETAMINOPHEN TOXICITY DIAGNOSTICS, LLC · PI JAMES, LAURA PHILLIPS · 2011 to 2018
$4.4M
AcetaSTAT Validation and CommercializationSB1DK079387 · NIDDK · ACETAMINOPHEN TOXICITY DIAGNOSTICS, LLC · PI JAMES, LAURA P · 2022 to 2025
$3.5M
Identification of new mechanistic biomarkers of adverse responses to acetaminopheR01DK081406 · NIDDK · ARKANSAS CHILDREN'S HOSPITAL RES INST · PI JAMES, LAURA P · 2009 to 2013
$1.9M
Dipstick Assay for Detection of Acetaminophen Protein AdductsR41DK079387 · NIDDK · ACETAMINOPHEN TOXICITY DIAGNOSTICS, LLC · PI JAMES, LAURA P · 2008 to 2010
$489k
NIDDK NIH HHS R01 DK081406NIDDK NIH HHS R41 DK079387NIDDK NIH HHS R42 DK079387NIDDK NIH HHS SB1 DK079387
6 · The paper itself

Abstract

BACKGROUND AND

aimHepatic phase I drug-metabolizing enzymes CYP2E1, CYP1A2 and CYP3A4 catalyze the biotransformation of Acetaminophen (APAP) and are important in the mediation of toxicity. The potential role of other hepatic and non-hepatic Phase I enzymes in APAP toxicity has not been established.

methodsPCR array containing 84 genes involved in phase I drug metabolism was examined in subgroups of hospitalized children for APAP overdose, categorized as no toxicity (ALT ≤ 45 IU/L, n=5) and moderate toxicity (ALT ≥ 500 IU/L, n=5).

resultsSignificant downregulation was observed for ALDH6A1, CYP4F12 and GZMB in the no toxicity subgroup and ALDH1A1, CYP27A1 and GZMB in the moderate toxicity subgroup. qRTPCR confirmed significant downregulation for ALDH1A1, CYP4F12, and GZMB. In-silico analysis identified GZMB 3'UTR to be a target of miR-378a-5p. Overexpression of miR-378a-5p reduced the luciferase activity of GZMB 3'UTR reporter plasmid reportedly by 50%. NK-92 cells transfected with the miR-378a-5p mimic extended the effect of APAP on GZMB protein expression compared to mimic controls. In addition, miR-378a-5p was significantly upregulated in blood samples of children with APAP overdose undergoing NAC treatment.

conclusionOverall, our study suggests the presence of a novel signaling pathway, whereby miR- 378a-5p inhibits GZMB expression in children with APAP overdose.

Indexed as

AcetaminophenAnalgesics, Non-NarcoticChemical and Drug Induced Liver InjuryChildCytochrome P-450 CYP1A2Cytochrome P-450 CYP2E1Cytochrome P-450 CYP3AGranzymesHumansInactivation, MetabolicMicroRNAsAcetaminophenAnalgesics, Non-NarcoticCYP1A2 protein, humanCYP3A4 protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP2E1Cytochrome P-450 CYP3AGranzymesGZMB protein, humanMicroRNAsMIRN378 microRNA, humanAcetaminophen (APAP)APAP-Induced Liver Injury (AILI)biomarkersCytochrome P450Granzyme BmiR-378a.

Identifiers

PMID31393259
PMCPMC10507677
OpenAlexW2968904325

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.