ArticleInfectious diseases and therapy2025
The Roles of Histone H3K18 Lactylation, Acetylation, and Lactylation/Acetylation Ratio as Potential Biomarkers in the Diagnosis and Severity Assessment of Sepsis and Septic Shock.
Article in Infectious diseases and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Review
- Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.Clinical epigenetics · 2026Review
- Qinggan Jianpi formula attenuates atherosclerosis by suppressing macrophage lactate transport to activate repair genes via H3K18 lactylation.Chinese medicine · 2026Article
- Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis.Cell death & disease · 2026Article
- Research progress on protein lactylation in female reproductive disease: molecular mechanisms, functions, and therapeutic implications.Frontiers in pharmacology · 2026Review
- Lactylation: a novel epigenetic bridge connecting metabolic reprogramming and immune dysregulation in sepsis-associated ARDS.Frontiers in immunology · 2026Review
- Histone lactylation-mediated glycolysis-ferroptosis axis in neurological diseases.Frontiers in molecular neuroscience · 2026Review
- RNA modifications shape innate immunity and cellular adaptation during bacterial respiratory infection.Frontiers in immunology · 2026Review
- Macrophage reprogramming and functional plasticity in sepsis.Frontiers in immunology · 2026Review
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Abstract
introductionThe complex pathophysiology and diverse clinical manifestations of sepsis and septic shock continue to make early diagnosis and severity assessment challenging. Previous studies revealed the distinct roles of histone H3 lysine 18 lactylation (H3K18la) and H3 lysine 18 acetylation (H3K18ac) in infection. However, the functions and interactions of these modifications remain unclear. This study aimed to investigate the expression and roles of H3K18la and H3K18ac in patients with sepsis and septic shock.
methodsThis ambispective cohort study enrolled 86 critically ill patients (13 sepsis, 37 septic shock, and 36 noninfectious) and 12 healthy volunteers. Baseline information and laboratory data were collected. H3K18la and H3K18ac levels in peripheral blood mononuclear cells were detected via Western blotting. Serum cytokines, arginase-1 (ARG1), and Krüppel-like factor 4 (KLF4) mRNA were assayed via microsphere immunofluorescence and quantitative real-time polymerase chain reaction. The potential value of H3K18la, H3K18ac, and their ratio (H3K18la/ac) in the diagnosis and severity assessment was analyzed using logistic regression, receiver operating characteristic curve, and correlation analysis.
resultsCompared with the noninfectious group, the infectious group presented increased H3K18la and H3K18la/ac and decreased H3K18ac levels, with H3K18la/ac as an independent diagnosis biomarker. Compared with the sepsis group, the septic shock group presented higher H3K18la and H3K18la/ac and lower H3K18ac levels. H3K18la and H3K18la/ac levels correlated positively with sequential organ failure assessment (SOFA) scores, length of intensive care unit (ICU) stay, and mechanical ventilation time. H3K18ac levels correlated negatively with SOFA scores and mechanical ventilation time. H3K18la levels correlated negatively with interferon-α (IFN-α) and interleukin‑5 (IL‑5) and positively with IL-10 expression. H3K18ac levels correlated negatively with IL-6, IL-1β, IL-8, and IL-10 expression. H3K18la/ac levels correlated negatively with IFN-α and IL-5 and positively with IL-6, IL-8, and IL-10 expression. H3K18la and H3K18la/ac correlated positively, whereas H3K18ac correlated negatively with ARG1 and KLF4 mRNA expression.
conclusionsH3K18la, H3K18ac, and H3K18la/ac can serve as biomarkers for the diagnosis and severity assessment of sepsis and septic shock through their involvement in inflammatory responses and macrophage polarization, thereby informing targeted therapies to modulate immune responses and improve patient outcomes.
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