Cervical cancer poses a significant threat to women’s health, and its metastasis is one of the leading causes of cancer-related deaths. Tubeimoside I (TBMS1) is a traditional Chinese medicinal herb with anticancer properties. We previously demonstrated the anticancer effect of TBMS1 in cervical cancer by inducing autophagy-related cell death. Nevertheless, whether and how TBMS1 prevents cervical cancer metastasis remain unclear. Wound healing, transwell assays, and a lung metastasis mouse model were used to evaluate cell metastasis. Immunoprecipitation combined with site-directed mutagenesis was used to explore ubiquitination modifications and ubiquitinated sites of histone deacetylase 5 (HDAC5). HDAC5 depletion and RNA-seq analysis were conducted to investigate the anti-metastatic mechanism of TBMS1. We show that low dose of TBMS1 inhibits cervical cancer metastasis. Mechanistically, TBMS1 binds to HDAC5 and prevents HDAC5 ubiquitination at lysine 137 and 538, leading to a decrease in proteasomal degradation of HDAC5. TBMS1-mediated HDAC5 upregulation further reduces the acetylation level of histone H3 lysine 27 (H3K27ac) and suppresses KPNA2 expression. HDAC5 depletion significantly attenuates TBMS1’s anti-metastatic effect in cervical cancer. Our study reveals HDAC5/H3K27ac/KPNA2 axis as the anti-metastatic mechanism of TBMS1 in cervical cancer, suggesting TBMS1 serves as a promising drug for cervical cancer treatment.

Current severe acute pancreatitis (SAP) murine models face significant limitations. The sodium taurocholate method consistently induces pancreatic necrosis but demands intricate surgical procedures, leading to high variability and infection risks. In contrast, the arginine approach causes acinar cell damage without fully mimicking clinical injury pathways. Furthermore, the caerulein-lipopolysaccharide (CAE-LPS) model, while operationally straightforward, fails to replicate persistent organ failure due to LPS’s rapid clearance, thereby inadequately capturing the lethal trajectory observed in clinical SAP patients who succumb to the disease. To address these gaps, we developed a SAP mouse model by integrating two key pathogenic mechanisms: trypsin-driven complement activation and sustained complement hyperactivation as drivers of multiple organ failure. The SAP model was established by combining CAE-induced pancreatic injury with zymosan (ZYM)-mediated complement activation. Dosing and combination protocols were meticulously optimized and were followed by a comprehensive longitudinal analysis during the acute phase (0–12 days), with comparisons to the CAE-LPS model. The optimized protocol involved nine intraperitoneal CAE injections (100 μg/kg each) followed by a single ZYM dose (1000 mg/kg). This regimen triggered pancreatic necrosis, inflammatory infiltration, and multi-organ damage (liver, kidney, intestine). Notably, the model demonstrated sustained complement activation and a mortality pattern in non-survivors that more closely aligned with clinical SAP outcomes than the CAE-LPS model. This novel model offers a robust platform for advancing SAP research, bridging the divide between preclinical studies and clinical translation.

Abstract Mesenchymal stem cells (MSCs) have a moderate impact on the therapy of severe acute pancreatitis. This study seeks to improve the therapeutic effectiveness of MSCs. By preconditioning them via the upregulation of critical anti‐inflammatory molecules, so diminishing immune rejection, we are creating a path for more effective treatments. Aloe emodin (AE), a natural active monomer with low‐toxicity, in conjunction with interferon gamma (IFN‐γ) (I‐AE), markedly upregulated immunosuppressive molecules indoleamine 2,3‐dioxygenase and programmed cell death‐Ligand 1 in MSCs, thereby pharmacologically modulating the inhibition of CD4 − T cell activation in vitro effectively. Transient transfection of small interfering RNA silenced the class II transactivator (CIITA) gene expression of umbilical cord mesenchymal stem cells (UMSCs) interfering with human leukocyte antigen class II expression to avert immune rejection. AE‐loaded nanoparticles efficiently maintained proliferation inhibition of MSCs within a manageable range by sustained release. UMSCs pretreated by I‐AE with CIITA silencing preserved pancreatic structure as evidenced by diminished acinar cell death, reduced pancreatic edema and inflammation, and significantly lowered serum amylase levels The encouraging potential of UMSCs with CIITA gene silencing combined with AE and IFN‐γ pretreatment offers optimism for clinical application in pancreatitis therapy.

Cancer cells cope with oxidative stress for their proliferation and metastasis by equipping antioxidant systems, among which the antioxidant enzymes peroxiredoxins (PRDXs) play crucial roles. However, whether PRDXs exhibit nonenzymatic functions remains unclear. Here, it is shown that the 1-cysteine PRDX (PRDX6) upregulates nicotinamide N-methyltransferase (NNMT) to promote the growth and metastasis of ovarian cancer cells, independently of PRDX6's enzymatic activities. Mechanistically, PRDX6 interacts with NNMT to prevent its binding to the E3 ubiquitin ligase tripartite-motif protein 56 (TRIM56), leading to the inhibition of NNMT ubiquitination at lysine 23 and 210 and suppression of subsequent proteasomal degradation. In addition, PRDX6-mediated NNMT upregulation activates mitogen-activated protein kinase (MAPK) signaling, thereby promoting the growth and metastasis of ovarian cancer cells. Notably, PRDX6 overexpression is associated with higher NNMT protein levels in human ovarian cancer tissues and is predictive of poor prognosis of ovarian cancer patients. Overall, the findings illustrate a critical oncogenic mechanism of the antioxidant enzyme PRDX6 in promoting ovarian cancer progression beyond its enzymatic mechanisms.