Genome modifications mediate the progression of inflammatory diseases by modulating the expression of related inflammatory genes (28). In our Research Topic, Lagosz-Cwik et al. found that the DNA methyltransferase (DNMT) inhibitor decitabine could suppress the proliferation of gingival fibroblasts (GFs) and induce necrotic cell death via reducing genome methylation. RNA sequencing showed that decitabine raised chemokines CCL-5, -8, -13, and -20, IL-1A, -18, -33, CSF3, the matrix metalloproteinases MMP-1, -9, and -13, and intercellular adhesion molecule-1 (ICAM-1), and reduced genes mediated collagen fibril and extracellular matrix organization, which suggests that DNMT inhibitors are potential agents against periodontitis pathogenesis. However, the potential cytotoxicity of DNMT inhibitors is a non-negligible challenge for their clinical applications. Jiang et al. explored the methylation level of Homeodomain-interacting protein kinase 3 (HIPK3) in blood using a sample database including 235 RA patients, 30 osteoarthritis (OA) patients, and 30 matched healthy controls. The results revealed that all 7 CpG islands are hypomethylated in RA patients compared with OA and healthy individuals. The 33286785 CpG displays the highest predictive power (AUC=0.829) against RA, and the prediction model could be further improved by combining HIPK3 with clinical index rheumatoid factors (RF⁺) and anti-citrullinated protein antibodies (ACPA⁻). Moreover, the study also found that the methylated HIPK3 levels are negatively correlated with C-reactive protein (CRP), suggesting that the blood methylation level of HIPK3 holds potential as a clinical diagnostic biomarker and indicator for CRP in RA. Shan et al. summarized the latest application advancements of the gamma-aminobutyric acid (GABA)ergic system (mainly consisting of GABA, GABA transporter, and GABA-related receptors) in RA theranostics, which provides an insight into the potential theoretical guidance and clinical choices for RA therapy. Zheng et al. summed up the functions of serine protease granzymes (Gzms) in RA pathogenesis and showed that these enzymes are potential targets for diagnosis and therapy for RA. Natoli et al. found that the DNA methylation profiles in CD4⁺ T-cells could discriminate the disease status of healthy controls, skin psoriasis, and psoriatic arthritis, which suggests that DNA methylation imprints may be used to determine the degree and grade of psoriasis, and thus to help carry out individualized therapeutic strategies accordingly. Sapienza et al. revealed the distinction in the DNA methylation profiles of diabetes patients who eventually developed end-stage renal disease (ESRD) and without diabetic nephropathy (DN) (29) and Wang et al. showed that this profile could be used to discriminate diabetes with ESRD and without DN. Zhang et al. described the immunoregulatory and metabolic roles and action mechanisms of genome methylation modification in the progression of metabolic-associated fatty liver disease (MAFLD), which provides references for the diagnosis and treatment of MAFLD via targeting nucleotide methylation. Xue et al. found that 8-oxoguanine DNA glycosylase1 (OGG1) inhibition or ablation enhances the antiviral activity of epithelial cells toward infection of human respiratory syncytial virus (RSV) in vitro and in vivo. Further study revealed that OGG1 recognizes 8-oxoGua in the vicinity of interferon response elements (IRF) within the IFN‐λ promoter, and thus reduces the DNA occupancy of NF-κB/RelA and IRFs by promoting the interaction between the NF-κB homodimer p50 and p50 in guanine islets (5’-GGG-3’) in the IFN‐λ promoter, which reduces IFN‐λ production, increases viral load and neutrophilia, and finally aggravates viral infection and immunopathology in mice. This finding indicates that OGG1 is a potential target for eliminating pulmonary viral infections in clinical settings.

Post-transcriptional modification refers to the various changes and alterations of RNA molecules after transcription from DNA (30). Post-transcriptional modifications including microRNA, lncRNA, tRNA, m⁶A modifications, etc. mediate various inflammatory diseases by modulating multiple immune components. Wang et al. systematically summarized the dysregulation of the miRNAs miR-183/96/182 cluster (miR-183C) in many autoimmune disorders, such as systemic multiple sclerosis, ocular autoimmune diseases, and lupus erythematosus, and highlighted the potential of miR-183C as targets for diagnosis markers and therapy against these autoimmune diseases. Wang et al. described the functions and mechanisms of non-coding RNAs including microRNAs, lncRNAs and m⁶A modifications in symptoms of podocytopathies, which provide a theoretical basis and target selection for the diagnosis and treatment of DN.

Post-translational modifications are also crucial epigenetic modes involved in accurately orchestrating a variety of inflammatory processes via writing, reading, and erasing marks of specific amino acid residues within proteins (31). Wang et al. showed that histone acetylation/de-acetylation modification in podocytopathy contributes to protecting from DN progression, which is a potential target for DN therapy.

Y-JL: Investigation, Writing – original draft. H-JZ: Conceptualization, Resources, Validation, Writing – review & editing. HW: Conceptualization, Investigation, Resources, Validation, Writing – review & editing. C-MC: Conceptualization, Formal Analysis, Resources, Validation, Writing – review & editing. G-JY: Conceptualization, Supervision, Writing – original draft, Writing – review & editing.