Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024229
CD40, a member of the tumor necrosis factor (TNF) receptor superfamily, plays an important role not only in the immune system but also in tumor progression. CD40 ligation reportedly promotes autophagy in immune cells. However, the effects of CD40 ligation on autophagy and its mechanism in solid tumor cells are still unclear. In this study, we find that CD40 ligation promotes autophagosome formation and consequently promotes autophagic flux in cervical cancer cells. Mechanistically, this effect relies on ERK contributing to CD40 ligation-induced ATG13 upregulation by p53. Furthermore, we demonstrate that CD40 ligation-induced autophagy increases the radiosensitivity of cervical cancer cells. Taken together, our results provide new evidence for the involvement of the CD40 pathway in autophagy and radiotherapy in cervical cancer cells.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261615
Ulcerative colitis (UC) remains a clinical challenge due to inadequate mucosal healing and high relapse rates. This study investigates the therapeutic efficacy of schisandrin B (Sch B) in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced rat model of UC, focusing on the interplay between autophagy and pyroptosis. SD rats were randomized into control, model, mesalazine (100 mg/kg), and Sch B low-, medium-, and high-dose (10, 20, 50 mg/kg) groups (n=10 per group). After 14 days of treatment, disease activity index (DAI), colon length, and colon mucosa damage index (CMDI) were assessed. Histopathology, serum cytokine levels (TNF-α, IL-6, IL-1β), and protein expression of autophagy markers (Beclin-1, LC3B, ATG16L1, p62) and pyroptosis pathway components (NLRP3, Caspase-1, GSDMD) were evaluated. Sch B significantly ameliorated weight loss, hematochezia, and colon shortening (P<0.05, 0.01), reduced DAI and CMDI scores, and attenuated mucosal edema, ulceration, and inflammatory infiltration. Serum IL-6, TNF-α, and IL-1β levels were markedly decreased (P<0.05, 0.01). Sch B upregulated Beclin-1 and increased LC3-II/I ratio (P<0.01), while downregulating ATG16L1, p62, NLRP3, Caspase-1, and GSDMD (P<0.05, 0.01). These findings indicate that Sch B restores autophagic flux homeostasis, thereby suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing pro-inflammatory cytokine release. The normalization of autophagic flux is a critical upstream mechanism for Sch B's inhibition of colonic epithelial pyroptosis, offering a multi-target therapeutic strategy for UC.