Evidence map›Paper›PMID 40733019›Full record

ReviewPharmaceutics2025

CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.

Yuchen Chen, Zoe Ann Tetz, Xindi Zeng, Sophia Jihye Go, Wenlu Ouyang, Kyung Eun Lee, Tao Dong, Yongqing Li, Jianjie Ma

Abstract readReview
In one paragraph

Review in Pharmaceutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Regulation of histones in thromboinflammation.Frontiers in immunology · 2026
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
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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

9 authors.

Yuchen ChenDivision of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.ORCID 0000-0001-8558-3062
Zoe Ann TetzDivision of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.ORCID 0009-0004-7853-6443
Xindi ZengDivision of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.
Sophia Jihye GoDivision of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.ORCID 0009-0006-3196-5456
Wenlu OuyangDepartment of Surgery, University of Michigan Health System, Ann Arbor, MI 48109, USA.ORCID 0000-0002-0610-2118
Kyung Eun LeeDivision of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.
Tao DongDepartment of Surgery, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Yongqing LiDepartment of Surgery, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Jianjie MaDivision of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.

Funding

Mitigating neuroinflammation and enhancing neuronal integrity in Alzheimer's diseaseR01AG072430 · NIA · UNIVERSITY OF VIRGINIA · PI Jianjie Ma · 2022 to 2026
$3.4M
NIA NIH HHS R01 AG072430
6 · The paper itself

Abstract

Neutrophils are essential components of innate immunity, executing a range of effector functions including phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). A key hallmark of NET formation is the presence of citrullinated histone H3 (CitH3), produced by peptidylarginine deiminases (PAD2 and PAD4) to facilitate chromatin decondensation. While NETs play critical antimicrobial roles, excessive or dysregulated NET formation, termed NETosis, can drive tissue injury, chronic inflammation, and organ dysfunction across a wide spectrum of diseases. Beyond its structural role within NETs, CitH3 acts as a damage-associated molecular pattern (DAMP), amplifying immune activation and pathological inflammation. Elevated CitH3 levels have been identified as biomarkers in sepsis, viral infections, ischemia-reperfusion injury, organ transplantation, diabetic wounds, autoimmune diseases, and cancer. Despite increasing recognition of CitH3's pathogenic contributions, its therapeutic potential remains largely untapped. This review summarizes recent advances in understanding the role of CitH3 in NETosis and immune dysfunction, highlights emerging strategies targeting CitH3 therapeutically, and identifies critical knowledge gaps. Collectively, these insights position CitH3 as a promising druggable biomarker for the diagnosis, prognosis, and treatment of acute and chronic inflammatory diseases.

Indexed as

antibody-based drugsautoimmune diseasesinfectioninflammationischemia–reperfusion injurysepsiswound healing

Identifiers

PMID40733019
PMCPMC12300630

What OpenQuestion holds

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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.