Histone lactylation is a metabolic stress‐related histone modification. However, the role of histone lactylation in the development of sepsis‐associated acute kidney injury (SA‐AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA‐AKI, which is reported in this study. Furthermore, this lactate‐dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA/Rho‐associated protein kinase (ROCK) /Ezrin signaling, the activation of nuclear factor‐κB (NF‐κB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA‐AKI and reportes a novel post‐translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA‐AKI.

Cardiovascular-Kidney-Metabolic (CKM) syndrome, a newly defined systemic disorder, is characterized by the pathological interplay among diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Recent studies have identified chronic inflammation not only as a central mediator in the pathological progression of CKM syndrome but also as a pivotal molecular hub that drives coordinated damage across multiple organ systems. Mechanistic investigations have revealed that aberrant activation of signaling pathways such as NF-κB, Wnt, PI3K-AKT, JAK-STAT, and PPAR constitutes a complex inflammatory regulatory network. Notably, these pathways facilitate inter-organ inflammatory crosstalk, establishing positive feedback loops among the heart, kidneys, and metabolic tissues. This, in turn, amplifies pathological processes such as oxidative stress, endothelial dysfunction, and fibrosis in a cascading manner.This review systematically delineates the multidimensional pathophysiological mechanisms of CKM syndrome, with particular emphasis on the inter-organ inflammatory regulation mediated by key signaling pathways. Furthermore, we explore the translational potential of therapeutic strategies targeting inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) based on the latest clinical evidence, aiming to provide a theoretical framework and novel perspectives for disrupting the vicious cycle of CKM syndrome.

Autoimmune diseases (AIDs) refer to connective tissue inflammation caused by aberrant autoantibodies resulting from dysfunctional immune surveillance. Most of the current treatments for AIDs use non-selective immunosuppressive agents. Although these therapies successfully control the disease process, patients experience significant side effects, particularly an increased risk of infection. There is a great need to study the pathogenesis of AIDs to facilitate the development of selective inhibitors for inflammatory signaling to overcome the limitations of traditional therapies. Immune cells alter their predominant metabolic profile from mitochondrial respiration to glycolysis in AIDs. This metabolic reprogramming, known to occur in adaptive immune cells, i.e., B and T lymphocytes, is critical to the pathogenesis of connective tissue inflammation. At the cellular level, this metabolic switch involves multiple signaling molecules, including serine–threonine protein kinase, mammalian target of rapamycin, and phosphoinositide 3-kinase. Although glycolysis is less efficient than mitochondrial respiration in terms of ATP production, immune cells can promote disease progression by enhancing glycolysis to satisfy cellular functions. Recent studies have shown that active glycolytic metabolism may also account for the cellular physiology of innate immune cells in AIDs. However, the mechanism by which glycolysis affects innate immunity and participates in the pathogenesis of AIDs remains to be elucidated. Therefore, we reviewed the molecular mechanisms, including key enzymes, signaling pathways, and inflammatory factors, that could explain the relationship between glycolysis and the pro-inflammatory phenotype of innate immune cells such as neutrophils, macrophages, and dendritic cells. Additionally, we summarize the impact of glycolysis on the pathophysiological processes of AIDs, including systemic lupus erythematosus, rheumatoid arthritis, vasculitis, and ankylosing spondylitis, and discuss potential therapeutic targets. The discovery that immune cell metabolism characterized by glycolysis may regulate inflammation broadens the avenues for treating AIDs by modulating immune cell metabolism.

Sepsis-associated acute kidney injury (SA-AKI) is a common complication in critically ill patients with high morbidity and mortality. SA-AKI varies considerably in disease presentation, progression, and response to treatment, highlighting the heterogeneity of the underlying biological mechanisms. In this review, we briefly describe the pathophysiology of SA-AKI, biomarkers, reference databases, and available omics techniques. Advances in omics technology allow for comprehensive analysis of SA-AKI, and the integration of multiple omics provides an opportunity to understand the information flow behind the disease. These approaches will drive a shift in current paradigms for the prevention, diagnosis, and staging and provide the renal community with significant advances in precision medicine in SA-AKI analysis.

Although the deregulation of lysine methyltransferase (su(var)-3–9, enhancer-of-zeste, trithorax) domain-containing protein 7/9 (SET7/9) has been identified in a variety of cancers, the potential role of SET7/9 and the molecular events in which it is involved in breast cancer remain obscure. Using the online Human Protein Atlas and GEO databases, the expression of SET7/9 was analyzed. Furthermore, we investigated the underlying mechanisms using chromatin immunoprecipitation-based deep sequencing (ChIP-seq) and quantitative ChIP assays. To explore the physiological role of SET7/9, functional analyses such as CCK-8, colony formation, and transwell assays were performed and a xenograft tumor model was generated with the human breast cancer cell lines MCF-7 and MDA-MB-231. Mass spectrometry, co-immunoprecipitation, GST pull-down, and ubiquitination assays were used to explore the mechanisms of SET7/9 function in breast cancer. We evaluated the expression of SET7/9 in different breast cancer cohorts and found that higher expression indicated worse survival times in these public databases. We demonstrated positive effects of SET7/9 on cell proliferation, migration, and invasion via the activation of Runt-related transcription factor 2 (RUNX2). We demonstrate that tripartite motif-containing protein 21 (TRIM21) physically associates with SET7/9 and functions as a major negative regulator upstream of SET7/9 through a proteasome-dependent mechanism and increased ubiquitination. Taken together, our data suggest that SET7/9 has a promoting role via the regulation of RUNX2, whereas TRIM21-mediated SET7/9 degradation acts as an anti-braking system in the progression of breast cancer.