Evidence map›Paper›PMID 39467260›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

CircFndc3b Mediates Exercise-Induced Neuroprotection by Mitigating Microglial/Macrophage Pyroptosis via the ENO1/KLF2 Axis in Stroke Mice.

Yun Zhao, Xiaofei He, Xiaofeng Yang, Zhongqiu Hong, Yin Xu, Jinghui Xu, Haiqing Zheng, Liying Zhang, Zejie Zuo, Xiquan Hu

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

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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

10 authors.

Yun ZhaoDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Xiaofei HeDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Xiaofeng YangDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Zhongqiu HongDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Yin XuDepartment of Rehabilitation, Zhujiang Hospital, Southern Medical University, 253 Industrial Middle Road, Guangzhou, Guangdong, 510282, China.
Jinghui XuDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Haiqing ZhengDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Liying ZhangDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Zejie ZuoDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
Xiquan HuDepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.ORCID 0000-0002-5554-6903

Funding

National Key R&D Program of China 2022YFC3601200National Natural Science Foundation of China 81871847National Natural Science Foundation of China 82172546National Natural Science Foundation of China 82272609National Natural Science Foundation of China 82402954Natural Science Foundation of Guangdong Province 2022A151512137Natural Science Foundation of Guangdong Province 2023A1515012695Natural Science Foundation of Guangzhou Science and Technology Bureau 202201020413
6 · The paper itself

Abstract

Circular RNA (circRNA) plays a pivotal role in regulating neurological damage post-ischemic stroke. Previous researches demonstrated that exercise mitigates neurological dysfunction after ischemic stroke, yet the specific contributions of circRNAs to exercise-induced neuroprotection remain unclear. This study reveals that mmu_circ_0001113 (circFndc3b) is markedly downregulated in the penumbral cortex of a mouse model subjected to middle cerebral artery occlusion (MCAO). However, exercise increased circFndc3b expression in microglia/macrophages, alleviating pyroptosis, reducing infarct volume, and enhancing neurological recovery in MCAO mice. Mechanistically, circFndc3b interacted with Enolase 1 (ENO1), facilitating ENO1's binding to the 3' Untranslated Region (3'UTR) of Krüppel-like Factor 2 (Klf2) mRNA, thereby stabilizing Klf2 mRNA and increasing its protein expression, which suppressed NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome-mediated microglial/macrophage pyroptosis. Additionally, circFndc3b enhanced ENO1's interaction with the 3'UTR of Fused in Sarcoma (FUS) mRNA, leading to increased FUS protein levels and promoting circFndc3b cyclization. These results suggest that circFndc3b mediates exercise-induced anti-pyroptotic effects via the ENO1/Klf2 axis, and a circFndc3b/ENO1/FUS positive feedback loop may potentiate exercise's neuroprotective effects. This study unveils a novel mechanism underlying exercise-induced neuroprotection in ischemic stroke and positions circFndc3b as a promising therapeutic target for stroke management, mimicking the beneficial effects of exercise.

Indexed as

Disease Models, AnimalKruppel-Like Transcription FactorsMacrophagesMicrogliaPhosphopyruvate HydratasePhysical Conditioning, AnimalPyroptosisAnimalsMaleMiceMice, Inbred C57BLNeuroprotectionRNA, CircularStrokeEno1 protein, mouseKlf2 protein, mouseKruppel-Like Transcription FactorsPhosphopyruvate HydrataseRNA, CircularcircFndc3bexerciseischemic strokemicroglianeurological dysfunction

Identifiers

PMID39467260
PMCPMC11714177

What OpenQuestion holds

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Registered trials

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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.