Evidence map›Paper›PMID 42455114›Full record

ArticleCNS neuroscience & therapeutics2026

Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.

Yijiang Jia, Ayijiang Taledaohan, Kai Wang, Maer Maer Tuohan, Rong Chen, Liujia Chan, Haoyu Shen, Di Zhu, Yuji Wang

Abstract read
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In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Yijiang JiaDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences of Capital Medical University, Beijing, China.ORCID https://orcid.org/0000-0002-3588-5334
Ayijiang TaledaohanDepartment of Emergency Medicine, University of California San Diego, San Diego, California, USA.ORCID https://orcid.org/0009-0006-5542-5999
Kai WangDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences of Capital Medical University, Beijing, China.ORCID https://orcid.org/0009-0001-1651-7560
Maer Maer TuohanDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences of Capital Medical University, Beijing, China.ORCID https://orcid.org/0009-0006-7815-7210
Rong ChenDepartment of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.ORCID https://orcid.org/0009-0007-7378-7050
Liujia ChanDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences of Capital Medical University, Beijing, China.ORCID https://orcid.org/0009-0008-0985-0104
Haoyu ShenDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences of Capital Medical University, Beijing, China.ORCID https://orcid.org/0009-0006-6885-4354
Di ZhuDepartment of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China.ORCID https://orcid.org/0000-0002-8959-2596
Yuji WangDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences of Capital Medical University, Beijing, China.ORCID https://orcid.org/0000-0003-3842-7627

Funding

National Outstanding Youth Science Fund Project of National Natural Science Foundation of China 22407094the Beijing High-Level Innovative and Entrepreneurial Talent Support Program "Capital High-End Leading Talent Gathering and Cultivation Project" 202504841074the Natural Science Foundation of Beijing Municipality for Young Scholars 2254070
6 · The paper itself

Abstract

aimsTo evaluate the neuroprotective potential of YJ-2, a novel peptidylarginine deiminase 4 (PAD4) inhibitor, against ischemia/reperfusion brain injury by targeting neutrophil extracellular trap (NET) formation.

methodsIn vitro, a NETs-induced injury model was established using SH-SY5Y and bEnd.3 cells. YJ-2's effects on viability, apoptosis, oxidative stress, and barrier permeability were assessed via CCK-8, flow cytometry, and FITC-dextran assays. In vivo, a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model received YJ-2 (10 μmol/kg) intravenously. Outcomes included infarct volume (TTC staining), neurological score, neuronal apoptosis (TUNEL), and oxidative markers (ELISA). PAD4 activity and histone H3 citrullination (H3cit) were examined by western blot and immunofluorescence.

resultsYJ-2 reduced NET-mediated neuronal death and oxidative stress in vitro, and improved endothelial barrier integrity. In MCAO/R rats, YJ-2 significantly lowered infarct volume (44.2% → 30.6%), improved neurological function, and suppressed apoptosis. It also decreased PAD4 and H3cit expression in ischemic brain tissue, confirming target engagement.

conclusionYJ-2, by preserving blood-brain barrier (BBB) integrity and reducing neuronal apoptosis, highlights its therapeutic potential for ischemic stroke.

Indexed as

Brain IschemiaEnzyme InhibitorsExtracellular TrapsNeuroprotective AgentsProtein-Arginine Deiminase Type 4AnimalsApoptosisBlood-Brain BarrierCell Line, TumorHumansInfarction, Middle Cerebral ArteryMaleMiceOxidative StressRatsRats, Sprague-DawleyEnzyme InhibitorsNeuroprotective AgentsProtein-Arginine Deiminase Type 4blood–brain barrierischemia/reperfusion injuryneuroprotectionneutrophil extracellular traps (NETs)PAD4 inhibitor

Identifiers

PMID42455114
PMCPMC13371606

What Socratic 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 Socratic graph.