Evidence map›Paper›PMID 32192500›Full record

ArticleJournal of neuroinflammation2020

Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury.

Zhongyuan Liu, Xinqiang Yao, Wangsheng Jiang, Wei Li, Siyuan Zhu, Congrui Liao, Lin Zou, Ruoting Ding, Jianting Chen

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed, 3 pooled it
27.5field-weighted citation impact, top 1% 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

199 citing papers in PubMed, 3 syntheses or guidelines pooled it, 417 citations in OpenAlex.

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139 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Zhongyuan LiuDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Xinqiang YaoDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Wangsheng JiangDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Wei LiDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Siyuan ZhuDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Congrui LiaoDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Lin ZouDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Ruoting DingDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. ding_ruoting@163.com.
Jianting ChenDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. chenjt99@tom.com.ORCID http://orcid.org/0000-0002-6957-4825
Nanfang Hospital · CN

Funding

National Natural Science Foundation of China 81772395
6 · The paper itself

Abstract

backgroundInflammatory response mediated by oxidative stress is considered as an important pathogenesis of spinal cord injury (SCI). Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress and their role in inflammatory response after SCI remained unclear. This study aimed to investigate the role of AOPPs in SCI pathogenesis and explore the possible underlying mechanisms.

methodsA C5 hemi-contusion injury was induced in Sprague-Dawley rats to confirm the involvement of AOPPs after SCI. For in vivo study, apocynin, the NADPH oxidase inhibitor was used to study the neuroprotective effects after SCI. For in vitro study, the BV2 microglia cell lines were pretreated with or without the inhibitor or transfected with or without small interference RNA (siRNA) and then stimulated with AOPPs. A combination of molecular and histological methods was used to clarify the mechanism and explore the signaling pathway both in vivo and in vitro. One-way analysis of variance (ANOVA) was conducted with Bonferroni post hoc tests to examine the differences between groups.

resultsThe levels of AOPPs in plasma and cerebrospinal fluid as well as the contents in the spinal cord showed significant increase after SCI. Meanwhile, apocynin ameliorated tissue damage in the spinal cord after SCI, improving the functional recovery. Immunofluorescence staining and western blot analysis showed activation of microglia after SCI, which was in turn inhibited by apocynin. Pretreated BV2 cells with AOPPs triggered excessive generation of reactive oxygen species (ROS) by activating NADPH oxidase. Increased ROS induced p38 MAPK and JNK phosphorylation, subsequently triggering nuclear translocation of NF-κB p65 to express pro-inflammatory cytokines. Also, treatment of BV2 cells with AOPPs induced NLRP3 inflammasome activation and cleavage of Gasdermin-d (GSDMD), causing pyroptosis. This was confirmed by cleavage of caspase-1, production of downstream mature interleukin (IL)-1β and IL-18 as well as rupture of rapid cell membrane.

conclusionsCollectively, these data indicated AOPPs as biomarkers of oxidative stress, modulating inflammatory response in SCI by multiple signaling pathways, which also included the induction of NADPH oxidase dependent ROS, and NLRP3-mediated pyroptosis, and activation of MAPKs and NF-κB.

Indexed as

Advanced Oxidation Protein ProductsAnimalsCell LineInflammationMaleMAP Kinase Signaling SystemMiceMicrogliaNF-kappa BOxidative StressPyroptosisRatsRats, Sprague-DawleySpinal Cord InjuriesAdvanced Oxidation Protein ProductsNF-kappa BAdvanced oxidation protein productsInflammatory responseMAPKs-NF-κB signaling pathwayNLRP3-mediated pyroptosisROS-dependentSpinal cord injury

Identifiers

PMID32192500
PMCPMC7082940
OpenAlexW3012588800

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.