{
  "abstract": "Type 3 cardiorenal syndrome (CRS3) is characterized by cardiac injury or dysfunction secondary to acute kidney injury (AKI), yet the contribution of AKI-associated metabolic remodeling to early myocardial inflammation remains poorly understood. Here, paired serum and myocardial untargeted metabolomics identified 1-methylhistidine (1-MH) as a metabolite elevated in both compartments, with the highest variable importance in projection score in serum. Exogenous 1-MH improved the E/A ratio and attenuated myocardial inflammation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positivity in rats with CRS3. Similar protective effects were observed in a separate post-ischemic cohort in which 1-MH was administered immediately after renal reperfusion. In CRS serum-exposed H9c2 cells, 1-MH reduced reactive oxygen species-associated fluorescence, malondialdehyde content, and intracellular Fe ²⁺ levels. Transcriptomic profiling showed that 1-MH suppressed inflammatory signaling, accompanied by changes in oxidative metabolism. Integration of these transcriptomic signatures with target prediction prioritized NFKB1/p105, while ensemble docking identified recurrent candidate interaction regions within p105. Cellular thermal shift assays showed a concentration-related increase in p105 thermal stability following 1-MH treatment. 1-MH increased p105 abundance while reducing total p50 abundance and nuclear p50 accumulation. p105 overexpression increased p50 abundance and the expression of inflammatory transcripts and proteins suppressed by 1-MH. These findings demonstrate that 1-MH attenuates early myocardial inflammation in CRS3 and reduces oxidative stress-related changes in CRS serum-exposed H9c2 cells. These functional results support modulation of the p105/p50 NF-κB axis and identify p105 as a molecular link between AKI-associated metabolic remodeling and myocardial inflammatory signaling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University",
    "Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiakun Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Qian Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xingyi Tu"
    },
    {
      "affs": [
        0
      ],
      "name": "Han Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Shihui Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingjie Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fpdqnjr3b8w7p.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1974807",
  "fulltext_url": "https://europepmc.org/articles/PMC13714413",
  "id": "fpdqnjr3b8w7p",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1974807/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",
      "2727|Acute Kidney Injury Research"
    ]
  ],
  "openalex": "W7221833767",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1974807/pdf",
  "pmcid": "PMC13714413",
  "pmid": "42953378",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fpdqnjr3b8w7p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1974807",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1974807/full"
    },
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953378",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953378"
    },
    {
      "first_seen": "2026-11-01T12:21:55Z",
      "native_id": "PMC13714413",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1974807"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "1-Methylhistidine attenuates early myocardial inflammation in type 3 cardiorenal syndrome through modulation of the p105/p50 NF-κB axis",
  "title_text": "1-Methylhistidine attenuates early myocardial inflammation in type 3 cardiorenal syndrome through modulation of the p105/p50 NF-κB axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:55Z",
  "url": "https://research.draconitic.com/paper/fpdqnjr3b8w7p",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}