Evidence map›Paper›PMID 34763084›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022

Circular RNA circ-FoxO3 attenuates blood-brain barrier damage by inducing autophagy during ischemia/reperfusion.

Zhenguo Yang, Cheng Huang, Xueyi Wen, Wenlin Liu, Xiaoxiong Huang, Yufeng Li, Jiankun Zang, Zean Weng, Dan Lu, Chi Kwan Tsang and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
  2. Exosomes in pathogenesis, diagnosis, and therapy of ischemic stroke.Frontiers in bioengineering and biotechnology · 2022
    Pooled it
  3. Article
  4. Review
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  7. Review
  8. Article
  9. Circular RNA PTPN4 Contributes to Blood-Brain Barrier Disruption during Early Epileptogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  10. Review
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  19. Article
  20. Small science · 2025
    Article

16 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

12 authors at 2 institutions in 1 country.

Zhenguo YangDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China; Affiliated Hospital of Guangdong Medical University, 57 South Renmin Ave, Zhanjiang 524001, China.
Cheng HuangDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Xueyi WenDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Wenlin LiuDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China; Affiliated Hospital of Guangdong Medical University, 57 South Renmin Ave, Zhanjiang 524001, China.
Xiaoxiong HuangDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Yufeng LiDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Jiankun ZangDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Zean WengDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Dan LuDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Chi Kwan TsangDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China.
Keshen LiDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China. Electronic address: likeshen1971@126.com.
Anding XuDepartment of Neurology and Stroke Center, The First Affiliated Hospital, & Clinical Neuroscience Institute of Jinan University, 613 West Huangpu Ave, Guangzhou 510632, China. Electronic address: tlil@jnu.edu.cn.
First Affiliated Hospital of Jinan University · CNGuangdong Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R. Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation. Mechanistically, we found that circ-FoxO3 inhibited mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity. These results demonstrate that circ-FoxO3 plays a novel role in protecting against BBB damage, and that circ-FoxO3 may be a promising therapeutic target for neurological disorders associated with BBB damage.

Indexed as

Brain IschemiaReperfusion InjuryAnimalsAutophagyBlood-Brain BarrierEndothelial CellsForkhead Box Protein O3HumansInfarction, Middle Cerebral ArteryMechanistic Target of Rapamycin Complex 1MiceReperfusionRNA, CircularForkhead Box Protein O3FOXO3 protein, humanMechanistic Target of Rapamycin Complex 1RNA, Circularautophagyblood-brain barriercircular RNA FoxO3E2F1hemorrhagic transfromationischemic strokemTORC1 complexproteins aggregates

Identifiers

PMID34763084
PMCPMC8899525
OpenAlexW3212261700

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.