Evidence map›Paper›PMID 33314534›Full record

ArticleCell proliferation2021

20-HETE synthesis inhibition attenuates traumatic brain injury-induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC-1α pathway: A translational study.

Wenxing Cui, Xun Wu, Yingwu Shi, Wei Guo, Jianing Luo, Haixiao Liu, Longlong Zheng, Yong Du, Ping Wang, Qiang Wang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell proliferation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 6% 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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  10. Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025
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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 1 institution in 1 country.

Wenxing CuiDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Xun WuDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Yingwu ShiDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Wei GuoDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Jianing LuoDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Haixiao LiuDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Longlong ZhengDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Yong DuDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Ping WangDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Qiang WangDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Dayun FengDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Shunnan GeDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Yan QuDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.ORCID https://orcid.org/0000-0001-5434-7390
Air Force Medical University · CN

Funding

National Natural Science Foundation of China 81630027
6 · The paper itself

Abstract

objectives20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid catalysed by cytochrome P450 enzymes and plays an important role in cell death and proliferation. We hypothesized that 20-HETE synthesis inhibition may have protective effects in traumatic brain injury (TBI) and investigated possible underlying molecular mechanisms. MATERIALS AND

methodsNeurologic deficits, and lesion volume, reactive oxygen species (ROS) levels and cell death as assessed using immunofluorescence staining, transmission electron microscopy and Western blotting were used to determine post-TBI effects of HET0016, an inhibitor of 20-HETE synthesis, and their underlying mechanisms.

resultsThe level of 20-HETE was found to be increased significantly after TBI in mice. 20-HETE synthesis inhibition reduced neuronal apoptosis, ROS production and damage to mitochondrial structures after TBI. Mechanistically, HET0016 decreased the Drp1 level and increased the expression of Mfn1 and Mfn2 after TBI, indicating a reversal of the abnormal post-TBI mitochondrial dynamics. HET0016 also promoted the restoration of SIRT1 and PGC-1α in vivo, and a SIRT1 activator (SRT1720) reversed the downregulation of SIRT1 and PGC-1α and the abnormal mitochondrial dynamics induced by 20-HETE in vitro. Furthermore, plasma 20-HETE levels were found to be higher in TBI patients with unfavourable neurological outcomes and were correlated with the GOS score.

conclusionsThe inhibition of 20-HETE synthesis represents a novel strategy to mitigate TBI-induced mitochondrial dysfunction and neuronal apoptosis by regulating the SIRT1/PGC-1α pathway.

Indexed as

AmidinesAnimalsApoptosisBrain Injuries, TraumaticDynaminsFemaleHumansHydroxyeicosatetraenoic AcidsLogistic ModelsMaleMiceMice, Inbred C57BLMiddle AgedMitochondriaMitochondrial DynamicsNeurons20-hydroxy-5,8,11,14-eicosatetraenoic acidAmidinesDNM1L protein, humanDynaminsHET0016Hydroxyeicosatetraenoic AcidsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseReactive Oxygen SpeciesSirt1 protein, mouseSirtuin 120-HETEapoptosismitochondrial dysfunctionSIRT1traumatic brain injury

Identifiers

PMID33314534
PMCPMC7848954
OpenAlexW3112765695

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.