Evidence map›Paper›PMID 41856250›Full record

ArticleJHEP reports : innovation in hepatology2026

Platelet hyperactivation drives oxidized mitochondrial DNA-induced neutrophil extracellular traps formation in biliary atresia.

Ledong Tan, Sige Ma, Rongchen Ye, Jiarou Shan, Yanlu Tong, Yixian Ren, Liuhong Meng, Zhe Wang, Zhe Wen, Fei Liu and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

17 authors.

Ledong TanProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Sige MaProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Liggins Institute, University of Auckland, Auckland, New Zealand.
Rongchen YeProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Jiarou ShanProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Yanlu TongProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Yixian RenInstitute of Occupational and Environmental Health, Guangzhou Medical University, Guangzhou, China.
Liuhong MengProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Zhe WangProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Zhe WenProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Fei LiuProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Xisi GuanProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Jiankun LiangProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Qifeng LiangProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Fuxing XuLuoyang Maternal and Child Health Hospital, Luoyang, China.
Ying WenProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address: wenying@gwcmc.org.
Ruizhong ZhangProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: zhangruizhong@gwcmc.org.
Huimin XiaProvincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsBiliary atresia (BA) is a progressive neonatal cholangiopathy characterized by unresolved inflammation and neutrophil extracellular traps (NET) formation. Although neutrophils contribute to bile duct injury, the upstream mechanisms driving their activation remain poorly defined. This study investigated whether platelet (PLT) hyperactivation promotes NET-mediated inflammation in BA and evaluated the therapeutic potential of targeting S100A8/A9.

methodsThe role of PLT hyperactivation in neutrophil-mediated inflammation in BA was evaluated through retrospective clinical review, single-cell RNA sequencing, and cell coculture experiments. The therapeutic potential of paquinimod, a small-molecule inhibitor that blocks S100A8/A9 binding to Toll-like receptor 4 on PLT and thereby suppresses PLT activation, was evaluated in a murine model of BA.

resultsElevated PLT counts were observed in 54.2% (236/435) of patients with BA, and PLT hyperactivation (CD62p

conclusionsPLT hyperactivation drives ox-mtDNA-dependent NET formation and amplifies inflammatory signaling in BA. Pharmacological inhibition of S100A8/A9 with paquinimod attenuates disease progression in mice. IMPACT AND IMPLICATIONS: Biliary atresia is a serious neonatal liver disease featuring bile duct inflammation and obstruction. Here, hyperactivated PLTs in biliary atresia patients released ox-mtDNA, triggering NET formation and exacerbating liver injury. Blocking the key inflammatory mediator S100A8/A9 with paquinimod reduced PLT activation and liver inflammation and improved survival in mice. These findings reveal a vicious immune cycle between PLTs and neutrophils and highlight novel treatment options for attenuating disease progression.

Indexed as

Biliary AtresiaBlood PlateletsDNA, MitochondrialExtracellular TrapsPlatelet ActivationAnimalsCalgranulin ACalgranulin BDisease Models, AnimalFemaleHumansMaleMiceNeutrophilsRetrospective StudiesCalgranulin ACalgranulin BDNA, MitochondrialBiliary injuryMitochondrial dysfunctionPaquinimodS100A8/A9Single-cell RNA sequencing

Identifiers

PMID41856250
PMCPMC13199776

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.