Wnt pathway inhibitor (Curegenix)

Endoplasmic reticulum (ER) stress is a key driver of tumor progression and therapeutic resistance. However, the prognostic role of ER stress-related long non-coding RNAs (lncRNAs) in cervical cancer has not been systematically elucidated. In this study, an ER stress-related lncRNA signature was constructed to evaluate patient prognosis and therapeutic responsiveness. Transcriptomic datasets derived from The Cancer Genome Atlas and the Genotype-Tissue Expression project were integrated, leading to the identification of 197 ER stress-associated differentially expressed genes and 1077 co-expressed lncRNAs. A prognostic 8-lncRNA model was developed using univariate/multivariate Cox regression and least absolute shrinkage and selection operator analysis. The model was validated by survival analysis (Kaplan–Meier and receiver operating characteristic curves), immune infiltration profiling (CIBERSORT and single-sample gene set enrichment analysis), and drug sensitivity analysis. Patients classified into the high-risk category showed significantly shorter overall survival (OS) (log-rank P < .001) and higher chemosensitivity to PI3K/mTOR inhibitors, whereas the low-risk group showed high immune activity (CD8+ T-cell infiltration and checkpoint expression) along with improved responsiveness to Wnt pathway inhibitors. The predictive capacity of the model (area under the curve, AUC: 0.806–0.856) exceeded that of conventional clinical parameters. Functional validation further revealed that LIPE-AS1, a representative high-risk lncRNA, promotes cervical cancer cell proliferation, migration, and invasion. These results introduce a novel ER stress-associated lncRNA signature with prognostic and therapeutic value, thus providing a potential basis for personalized immunotherapeutic and chemotherapeutic strategies in cervical cancer.

Cartilage injury would trigger a chronic inflammatory microenvironment that disrupts tissue regeneration and accelerates the onset of osteoarthritis (OA). However, current treatments primarily focus on the symptomatic relief of OA but fail to address the underlying pathophysiological issues. Herein, we developed an injectable Ca²⁺/Sr²⁺-crosslinked hydrogel incorporating LGK-974/polydopamine nanoparticles for immune regulation and cartilage regeneration. Given the pivotal role of Wnt signaling activation in OA, LGK-974, a Wnt pathway inhibitor targeting the key upstream component (Porcupine) was first integrated for OA prevention. It came out that Sr²⁺ optimized the physical properties of the modified hydrogel and synergistically released with LGK-974, which potently suppressed the Wnt/β-catenin pathway, effectively promoted M2 macrophage polarization, reactive oxygen species (ROS) scavenging, chondrocytes proliferation and extracellular matrix (ECM) secretion. In vivo studies further confirmed that the hydrogel significantly promoted cartilage repair and stimulated ECM regeneration. Building on the pathogenesis of OA, this study suggests that the novel injectable hydrogel holds great promise as an effective therapeutic strategy for promoting cartilage repair and preventing OA progression through minimally invasive intervention.