The Second Hospital of Shandong University

Oxidative stress, characterized by an imbalance between excessive reactive oxygen species (ROS) production and impaired antioxidant defenses, is closely linked to the pathogenesis of various otorhinolaryngological disorders. Mitochondria, as the primary site of cellular energy production, play a crucial role in modulating oxidative stress. Mitochondrial dysfunction exacerbates ROS generation, leading to cellular damage and inflammatory responses. In otorhinolaryngological diseases, oxidative stress is strongly associated with conditions such as hearing loss, allergic rhinitis, and chronic sinusitis, where oxidative damage and tissue inflammation are key pathological features. Recent studies have highlighted the potential of antioxidant therapies to mitigate oxidative stress and restore homeostasis, offering promising avenues for alleviating symptoms in these diseases. However, despite the encouraging results from early-stage research, the clinical efficacy of antioxidant interventions remains to be fully established. This review provides an overview of the role of oxidative stress in otorhinolaryngological diseases and evaluates the therapeutic potential of antioxidant strategies.

Gastric cancer remains one of the deadliest cancers globally due to delayed detection and limited treatment options, underscoring the critical need for innovative prognostic methods. Disulfidptosis, a recently discovered programmed cell death triggered by disulphide stress, presents a fresh avenue for therapeutic exploration. This research examines disulfidptosis-related long noncoding RNAs (DRLs) in gastric cancer, with the goal of leveraging these lncRNAs as potential markers to enhance patient outcomes and treatment approaches. Comprehensive genomic and clinical data from stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA). Employing least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic model was devised incorporating five key DRLs to forecast survival rates. The effectiveness of this model was validated using Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, and extensive functional enrichment studies. The importance of select lncRNAs and the expression variability of genes tied to disulfidptosis were validated via quantitative real-time PCR (qRT-PCR) and Western blot tests, establishing a solid foundation for their prognostic utility. Analyses of functional enrichment and tumour mutation burden highlighted the biological importance of these DRLs, connecting them to critical cancer pathways and immune responses. These discoveries broaden our comprehension of the molecular framework of gastric cancer and bolster the development of tailored treatment plans, highlighting the substantial role of DRLs in clinical prognosis and therapeutic intervention.

Combination therapies show promise for glioblastoma (GBM) treatment, however, insufficient drug accumulation in the brain and significant toxic side effects continue to pose critical challenges to therapeutic efficacy. Here, we report an intranasal ion-sensitive hydrogel (IHG) platform for efficient co-delivery of TMZ and disulfiram (DSF) to GBM via the nose-to-brain pathway. The optimized IHG formulation demonstrates superior gelation properties, sustained drug release, and enhanced brain accumulation, achieving remarkable drug targeting efficiency (468.9 %) and direct transport percentage (80.3 %). Within the tumor microenvironment, in situ-generated TMZ and the chelation product of DSF and copper ions (CuET) synergistically induce DNA damage and apoptosis, thereby enhancing tumor cell sensitivity to TMZ. Furthermore, tdIHG+Cu induces robust immunogenic cell death, stimulates CXCL10 release, mediates dendritic cell maturation, and promotes CD8⁺ T cell infiltration, thereby establishing a potent antitumor immune response. This approach not only demonstrates superior therapeutic efficy against GBM progression through enhanced intracranial drug accumulation and optimized drug ratios, but also minimizes systemic toxicity via localized delivery. Our findings offer a potentially clinical translatable strategy worth further investigation.