Acute pancreatitis (AP) can be mild and self-limited, but it can also become severe acute pancreatitis (SAP) and lead to multi-organ dysfunction. It is still difficult to identify patients who may develop severe disease at an early stage. Lactate was once viewed only as a metabolic byproduct, but recent work shows that it also acts as a signaling molecule that links cellular energy status with immune control. Its role in the progression of AP is still not clear. Transcriptomic analysis showed clear differences in metabolism and immune features between SAP and non-severe AP (NSAP). Among lactate-related genes (LRGs), 24 were expressed at different levels. Three machine-learning methods identified CCNA2 and H2BC5 as possible diagnostic markers. Both genes had higher expression in SAP clinical samples. In vitro experiments showed that adding lactate increased CCNA2 and H2BC5 expression and raised inflammatory cytokine production. When these genes were knocked down, the inflammatory response decreased. This suggests that both genes are involved in lactate-driven inflammatory signaling. Molecular docking and simulation showed that the MDM2 inhibitor AMG-232 binds strongly to CCNA2, and the mTOR inhibitor Torin-1 binds strongly to H2BC5. Functional tests showed that Torin-1 reduced inflammation and oxidative stress in a sodium-taurocholate–induced cell model. This study shows that CCNA2 and H2BC5 are candidate biomarkers for SAP. They are involved in important immune and metabolic pathways. AMG-232 and Torin-1 are possible therapeutic drugs. These findings give a molecular framework for early risk detection in AP and point to new options for targeted treatment. The online version contains supplementary material available at 10.1186/s13036-025-00605-w.

The present study investigated the distinct metabolic profiles of two primary traditional Chinese medicine (TCM) syndromes in patients with cholelithiasis—liver Qi stagnation (LQS) and liver-gallbladder damp-heat (LGDH). By integrating untargeted and targeted metabolomics, we aimed to identify objective serum and urine biomarkers for syndrome differentiation and to elucidate their underlying biological basis. In total, 91 participants, comprising 33 healthy controls (HCs), 30 cholelithiasis patients with LQS syndrome, and 28 cholelithiasis patients with LGDH syndrome, were enrolled. Untargeted analysis of serum and urine samples quantified 602 and 636 metabolites, respectively. To strengthen the robustness of the dataset, complementary targeted metabolomics was conducted as an orthogonal validation step, providing reliable quantification for 210 serum and 204 urinary. The present findings provide molecular insights into the TCM principle of syndrome differentiation (Bian Zheng Lun Zhi). The identified biomarker panel may offer a basis for developing objective tools for the stratification of cholelithiasis syndromes and may support future efforts towards personalized therapeutic strategies.

Environmental cadmium (Cd) pollution poses a severe threat to human health due to its strong bioaccumulation and high carcinogenicity. Although Cd exposure has been linked to various cancers, its specific role in pancreatic cancer (PC) remains unclear. This study aimed to explore the molecular mechanisms underlying Cd-associated PC and identify potential diagnostic and therapeutic targets. Transcriptomic data of PC were obtained from the GEO database to screen differentially expressed genes (DEGs), which were then intersected with Cd-related genes retrieved from the Comparative Toxicogenomics Database (CTD). Functional enrichment analyses, including GO and KEGG, were conducted to identify key biological processes and pathways. Multiple machine learning algorithms were used to construct a diagnostic model and identify hub genes. Furthermore, molecular docking and molecular dynamics simulations were performed to evaluate drug-target interactions, and in vitro experiments were used to validate the effects of Cd exposure on PC cell proliferation and invasiveness. A total of five key genes-FN1, COL5A1, AHR, COL3A1, and TIMP1-were identified as core regulators of Cd-associated PC. Functional analyses indicated that Cd primarily affects the extracellular matrix (ECM) metabolic and collagen remodeling pathways. Experimental results confirmed that Cd exposure significantly enhanced the proliferation and invasiveness of PC cells. Molecular docking and dynamics simulations revealed that the EGFR inhibitor dacomitinib exhibited favorable predicted binding affinity to FN1, suggesting its potential as a therapeutic agent. This study reveals that Cd may promote the malignant progression of PC by regulating ECM remodeling through key genes such as FN1. Dacomitinib shows promise as an FN1-associated therapy, offering new insights for the precise prevention and treatment of Cd-associated PC.