Tanshinone IIA, a bioactive lipophilic diterpenoid from Salvia miltiorrhiza Bunge (Lamiaceae), exhibits anti-tumor effects but is limited by poor pharmacokinetic properties. Building on our previously reported tanshinone IIA-derived imidazole analogue (1), we systematically evaluated its anti-hepatocellular carcinoma (HCC) activity and investigated its effects on VEGFR2 signaling in relation to autophagy. In vitro, compound 1 inhibited HepG2 colony formation and migration while inducing minimal apoptosis. Immunofluorescence revealed altered paxillin distribution and reduced FAK expression. In VEGF-induced and tumor-induced angiogenesis models using transgenic zebrafish (Tg-fli1a: EGFP), compound 1 suppressed ectopic vessel sprouting and reduced HepG2 xenograft growth. Notably, compound 1 treatment dose-dependently suppressed VEGFR2 phosphorylation without altering total VEGFR2 expression in both HepG2 cells and VEGF-stimulated endothelial cells. Concurrently, compound 1 induced autophagic features (LC3-II accumulation and autolysosome formation) and downregulated the PI3K/AKT/mTOR pathway. These findings indicate that compound 1 exerts dual anti-angiogenic and anti-tumor effects in HCC, with VEGFR2 phosphorylation inhibition as a key contributing pathway.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that regulate diverse physiological processes in neuronal and non-neuronal tissues. In recent years, increasing evidence has shown that nAChRs are also expressed in many cancer cell types, where they contribute to tumor growth, survival, angiogenesis, migration, invasion, and resistance to therapy. The involvement of distinct receptor subunits in these processes has generated interest in nAChRs as potential therapeutic targets in oncology. However, conventional pharmacological agents often show limited subtype selectivity and may produce off-target effects because of the widespread distribution of these receptors in normal tissues. Small interfering RNA (siRNA) offers a more selective strategy by enabling sequence-specific silencing of individual nAChR subunits implicated in malignant behavior. This review highlights the structural and functional characteristics of nAChRs, the rationale for targeting specific subunits in cancer, and the mechanisms by which siRNA can suppress receptor expression. Particular attention is given to experimental studies evaluating the silencing of nAChR subunits in cancer models and to the therapeutic implications of combining receptor-specific siRNA with established anticancer agents. In addition, key translational barriers are discussed, including delivery challenges, instability, off-target effects, immune activation, and tumor heterogeneity. Although the field remains largely preclinical, available findings support the concept that nicotinic receptor-specific siRNA may serve as a promising precision strategy for cancer treatment and may improve treatment responsiveness in selected malignancies.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with limited therapeutic options, highlighting the urgent need for novel anti-tumor agents. Oridonin, a bioactive diterpenoid derived from Isodon rubescens, has demonstrated broad-spectrum anticancer activities. However, its precise role in NPC remains largely undefined. This study investigated the anti-NPC effects of oridonin and its underlying mechanisms. In vitro, oridonin significantly inhibited NPC cell proliferation and migration, while enhancing sensitivity to copper ionophore-induced cell death. Mechanistically, transcriptomic analysis and subsequent validation revealed that oridonin transcriptionally upregulates FDX1, a key regulator of cuproptosis, and directly binds to FDX1 with high affinity. FDX1 knockdown substantially abrogated oridonin-induced cuproptosis, as evidenced by reduced DLAT oligomerization/aggregation (indicative of reduced lipoylated DLAT aggregation) and resistance to copper ionophores, confirming that FDX1 is a critical downstream effector of oridonin. In vivo, oridonin significantly suppressed tumor growth in xenograft models, accompanied by elevated intra-tumoral copper levels and increased FDX1 and DLAT expression. Collectively, these findings demonstrate that oridonin exerts anti-NPC activity by targeting FDX1 to induce cuproptosis, highlighting oridonin as a promising therapeutic candidate for NPC treatment.

Vaginal mucosal inflammation (VMI) injury results in loss of epithelial integrity and mucosal injury, predisposing women to infections and reproductive complications; however, effective therapies that promote mucosal repair remain limited. Here, we investigated the effects of mussel adhesive protein (MAP), type III collagen (COL III), and β-glucan on the lipopolysaccharide (LPS)-induced VMI injury model. The VMI injury cellular model was constructed by using LPS-induced human vaginal epithelial cells. We optimized the concentration of the above three agents and evaluated the effects of MAP, COL III, and β-glucan on proliferation, migration, antioxidant capacity, and inflammatory factors. The results suggested that the MAP had no effect on migration and proliferation, and no further investigation of the MAP was performed, as this result indicated that the MAP failed to meet the main purpose of the present study. The combination of COL III and β-glucan promoted migration and proliferation compared with the control group (P < 0.05, as indicated by scratch closure). However, none of the treatments significantly alter inflammatory cytokine levels or antioxidant activity under the present experimental conditions (P > 0.05). Transcriptomic profiling revealed that treatments of COL III and β-glucan were associated with distinct transcriptional changes enriched in stress adaptation and tissue repair-related pathways, accompanying the enhanced epithelial migration and proliferation, without markedly affecting classical inflammatory cytokine expression. These findings suggest that COL III and β-glucan may promote epithelial repair and that the observed transcriptional alterations are associated with this response.

PIWI-associated RNAs (piRNAs) are a diverse and abundant class of small regulatory non-coding RNAs that play central roles in genome regulation and transposon silencing. First identified in germline cells, piRNAs are now also implicated in somatic cell function, stem cell maintenance, immunity, and human disease, particularly cancer and neurodegeneration. This review follows the evolution of piRNA research, highlighting advances in their biogenesis, molecular mechanisms, and multifaceted roles in gene regulation. It also outlines how recent computational developments, especially deep learning and network-based models, together with dedicated databases and web tools, have improved functional and disease-association prediction, and discusses emerging clinical applications of piRNAs as diagnostic biomarkers and therapeutic targets at the frontiers of RNA-based precision medicine.