Ultrasound-assisted cerium-doped zeolite nanocomplex attenuates adenomyosis by inhibiting Wnt/beta-catenin and downregulating IGFBP5

Adenomyosis is a chronic gynecological disorder marked by ectopic endometrial tissue within the myometrium, leading to severe pelvic pain, menorrhagia, and infertility. Current treatments, often hormonal or surgical, have limitations in efficacy and adverse effects. Emerging evidence points to dysregulated Wnt/beta-catenin signaling and aberrant activation of SFRP4+ natural killer T (NKT) cells as key drivers of disease progression. Targeting these pathways offers a promising avenue for developing novel, non-hormonal therapeutic strategies to address the underlying pathology of adenomyosis.

Researchers synthesized a cerium-doped zeolite nanocomplex (Ce-ZNC) using an ultrasound-assisted doping approach. The nanocomplex was thoroughly characterized for morphology, size, and stability using TEM, XRD, FTIR, DLS, and PDI analyses. In vitro experiments were performed on human peripheral blood mononuclear cell (PBMC)-derived SFRP4+ NKT cells to assess cellular effects. In vivo efficacy was evaluated in a murine model of adenomyosis. Expression of IGFBP5 and components of Wnt/beta-catenin signaling were analyzed via RT-qPCR and Western blotting. Histological and cytokine analyses were also conducted to quantify fibrosis and inflammation.

The synthesized Ce-ZNC exhibited a spherical morphology with nanoscale dimensions and demonstrated good colloidal stability. In vitro, treatment with Ce-ZNC resulted in a dose-dependent suppression of IGFBP5 expression and a clear inhibition of Wnt/beta-catenin signaling within SFRP4+ NKT cells. These cellular effects translated into significant therapeutic benefits in the in vivo murine model of adenomyosis. > In vivo administration of Ce-ZNC significantly reduced uterine fibrosis, glandular invasion, and inflammatory cytokine levels, suggesting potent immunomodulatory and anti-fibrotic actions.The observed reductions in disease markers underscore the nanocomplex's ability to modulate key pathological pathways associated with adenomyosis progression. While specific numerical reductions or p-values were not detailed in the abstract, the consistent 'significant' and 'dose-dependent' findings highlight a robust therapeutic effect.