Evidence map›Paper›PMID 42159900›Full record

ArticleInflammopharmacology2026

Inhibiting pyruvate carboxylase as a potential therapeutic strategy for alleviating rheumatoid arthritis.

Szu-Wei Huang, Hui-Chun Yu, Hsien-Bin Huang, Pin-Chen Chen, Ming-Chi Lu

Abstract read
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In one paragraph

Article in Inflammopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

1 citing paper in PubMed.

  1. Review
4 · The record

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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

5 authors.

Szu-Wei HuangDepartment of Veterinary Medicine, National Chiayi University, Chiayi City, Taiwan.
Hui-Chun YuDivision of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. junvsusagi@gmail.com.
Hsien-Bin HuangDepartment of Biomedical Sciences, National Chung Cheng University, Minxiong, Chiayi, Taiwan.
Pin-Chen ChenDivision of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan.
Ming-Chi LuDivision of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. e360187@yahoo.com.tw.

Funding

Dalin Tzu Chi Hospital DTCRD113-I-01-01Ministry of Science and Technology, Taiwan MOST 111-2314-B-303 -007 -MY3National Science and Technology Council NSTC 114-2314-B-303 -024 -MY3
6 · The paper itself

Abstract

backgroundRheumatoid arthritis (RA) is marked by synovial inflammation, cartilage loss, and bone erosion, with macrophages playing a central role. Pyruvate carboxylase (PC), a mitochondrial enzyme, has been linked to inflammation, but its role in RA is unclear.

methodsWe investigated the effects of pharmacological PC inhibition with ZY-444 in a collagen antibody-induced arthritis (CAIA) mouse model and assessed disease severity, cytokine production, and histopathology. In vitro, PC expressions were analyzed in U937 cells, macrophages, and LPS-activated macrophages. Functional analysis of PC knockdown was evaluated using qRT-PCR, ELISA, Western blotting, and apoptosis assays.

resultsIn CAIA mice, ZY-444 treatment significantly reduced clinical severity, joint inflammation, macrophage infiltration, and histological severity, with efficacy comparable to dexamethasone. ZY-444 suppressed TNF-α and IL-6 in joints and decreased serum IL-6. In vitro, PC expression increased during macrophage differentiation and activation, while PC knockdown markedly reduced cytokine expression and secretion. Mechanistically, PC deficiency attenuated mitogen-activated protein kinase (MAPK) phosphorylation, enhanced macrophage apoptosis, and upregulated HIF-1α expression.

conclusionsPC regulates macrophage-driven inflammation in RA. Its inhibition alleviates disease pathology, supporting PC as a therapeutic target and ZY-444 as a potential repurposed anti-inflammatory agent.

Indexed as

Arthritis, ExperimentalArthritis, RheumatoidPyruvate CarboxylaseAnimalsAnti-Inflammatory AgentsApoptosisCytokinesHumansInflammationMacrophagesMaleMiceMice, Inbred DBAU937 CellsAnti-Inflammatory AgentsCytokinesPyruvate CarboxylaseHIF-αMacrophagesMAPKsPyruvate carboxylaseRheumatoid arthritis

Identifiers

PMID42159900

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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.