Evidence map›Paper›PMID 36097583›Full record

ArticleJHEP reports : innovation in hepatology2022

Acetaminophen-induced reduction of NIMA-related kinase 7 expression exacerbates acute liver injury.

Zhenzhen Sun, Qian Wang, Le Sun, Mengying Wu, Shuzhen Li, Hu Hua, Ying Sun, Tong Ni, Chunlei Zhou, Songming Huang and 3 more

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

Article in JHEP reports : innovation in hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.2field-weighted citation impact, top 9% 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, 18 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

13 authors at 2 institutions in 1 country.

Zhenzhen SunNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Qian WangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Le SunNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Mengying WuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Shuzhen LiNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Hu HuaNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Ying SunJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Tong NiNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Chunlei ZhouDepartment of Pathology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Songming HuangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Aihua ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yue ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Zhanjun JiaNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Second Affiliated Hospital of Nanjing Medical University · CNXuzhou Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: Acetaminophen (APAP)-induced acute liver injury (ALI) is a global health issue characterised by an incomplete understanding of its pathogenesis and unsatisfactory therapies. NEK7 plays critical roles in both cell cycle regulation and inflammation. In the present study, we investigated the role and mechanism of NEK7 in APAP-induced ALI. Methods: In mice with NEK7 overexpression (hydrodynamic tail vein injection of NEK7 plasmids), hepatocyte-specific NEK7 knockout (cKO), and inducible NEK7 knockout (iKO), an overdose of APAP was administered to induce ALI. Liver injury was determined by an analysis of serum liver enzymes, pathological changes, inflammatory cytokines, and metabonomic profiles. Results: NEK7 was markedly downregulated in APAP-induced injured liver and damaged hepatocytes. NEK7 overexpression in the liver significantly alleviated APAP-induced liver injury, as shown by the restored liver function, reduced pathological injury, and decreased inflammation and oxidative stress, which was confirmed in a hepatocyte cell line. Moreover, both NEK7 cKO and iKO mice exhibited exacerbation of APAP-induced ALI. Finally, we determined that cyclin B1-mediated cell cycle progression could mediate the protective effect of NEK7 against APAP-induced ALI. Conclusions: Reduced NEK7 contributes to APAP-induced ALI, possibly by dysregulating cyclins and disturbing cell cycle progression. Lay summary: Acetaminophen-induced acute liver injury is one of the major global health issues, owing to its high incidence, potential severity, and limited therapeutic options. Our current understanding of its pathogenesis is incomplete. Herein, we have shown that reduced NEK7 (a protein with a key role in the cell cycle) exacerbates acetaminophen-induced acute liver injury. Hence, NEK7 could be a possible therapeutic target for the prevention or treatment of this condition.

Indexed as

ALF, acute liver failureALI, acute liver injuryALT, alanine aminotransferaseAPAP, acetaminophenApoptosisAST, aspartate aminotransferaseCCK-8, cell counting kit 8cKO mice, conditional knockout miceCtrl, controlCYP2E1GSH, glutathioneHet, heterozygousiKO mice, inducible knockout miceLDH, lactate dehydrogenaseMCP-1, monocyte chemoattractant protein-1MDA, malondialdehydeNAPQI, N-acetyl-p-benzoquinone imineND1, NADH dehydrogenase 1NEK7, NIMA-related kinase 7NLRP3PI, propidium iodideROS, reactive oxygen speciessi, small interferingTNF-α, tumour necrosis factor-alphaTPM, transcripts per kilobase of exon model per million mapped readsWT, wild-type

Identifiers

PMID36097583
PMCPMC9463592
OpenAlexW4286256319

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.