{
  "abstract": "Background: Primary non-response (PNR) to infliximab (IFX) remains a major therapeutic challenge in ulcerative colitis (UC). However, the molecular mechanisms underlying this treatment failure remains unelucidated. Therefore, there is an urgent need to identify the key drivers of PNR and develop effective interventions to improve therapeutic outcomes.\n\nMethods: Human colonic RNA-sequencing data were analyzed to identify molecular features associated with PNR to IFX. Immune infiltration analysis, clinical sample validation, virtual gene knockout, and single-cell RNA sequencing were performed to characterize the immune landscape, identify the key regulatory molecule, and elucidate its underlying mechanisms and cellular source. Network pharmacology and molecular docking were employed to identify a potential therapeutic strategy targeting the key regulatory molecule, followed by mechanistic and functional validation in cell-based assays and therapeutic evaluation in a DSS-induced murine colitis model.\n\nResults: Excessive colonic neutrophil infiltration marked PNR in UC prior to IFX treatment. PTGS2 positively correlated with neutrophil infiltration and was predominantly expressed in colonic CD14 ⁺ S100A9 ⁺ inflammatory monocytes. Virtual knockout of PTGS2 altered genes related to neutrophil chemotaxis, which were primarily enriched in the NF-κB signaling axis. Gegen Qinlian Decoction (GQD), a traditional Chinese herbal formula, was identified to target PTGS2 through multiple bioactive constituents, with quercetin exhibiting the highest binding affinity. Quercetin suppressed LPS-induced PTGS2 expression in inflammatory monocytes, thereby inhibiting the NF-κB/CXCL8 signaling and attenuating neutrophil chemotaxis, as further supported by PTGS2 knockdown and overexpression experiments. In vivo , GQD markedly reduced PTGS2 expression and neutrophil accumulation in the inflamed colon, thereby significantly ameliorating disease severity and enhancing IFX responsiveness in DSS-induced colitis.\n\nConclusion: Monocyte-derived PTGS2 contributes to primary IFX non-response by promoting neutrophil recruitment in UC. GQD improves IFX responsiveness by suppressing PTGS2-associated inflammatory signaling and neutrophil recruitment, highlighting its potential as a therapeutic strategy to enhance IFX efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Digestive Diseases, The Second Hospital and Clinical Medical School, Lanzhou University",
    "Department of Gastroenterology, The Second Hospital and Clinical Medical School, Lanzhou University",
    "MeDiC Program, The Research Institute of McGill University Health Centre and Division of Endocrinology and Metabolism, Department of Medicine, McGill University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Dan Pu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaojuan Kang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lingzhu Gou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoli Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Pengfei Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Guoqing Qi"
    },
    {
      "affs": [
        2
      ],
      "name": "Jun-Li Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Dekui Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7twjn1gf3x3tx.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1957588",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727455/?tool=EBI",
  "id": "7twjn1gf3x3tx",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1957588/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7223000134",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727455/pdf/?tool=EBI",
  "pmcid": "PMC13727455",
  "pmid": "42978631",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/7twjn1gf3x3tx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1957588",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1957588/full"
    },
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13727455",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727455"
    },
    {
      "first_seen": "2026-11-06T12:23:19Z",
      "native_id": "PMC13727455",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1957588"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Inflammatory Bowel Disease",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Overcoming primary non-response to infliximab in ulcerative colitis: monocyte-derived PTGS2 as a therapeutic target",
  "title_text": "Overcoming primary non-response to infliximab in ulcerative colitis: monocyte-derived PTGS2 as a therapeutic target",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:38Z",
  "url": "https://research.draconitic.com/paper/7twjn1gf3x3tx",
  "venue": "Frontiers in Immunology",
  "versions": []
}