Enhanced autophagy alleviated corneal allograft rejection via inhibiting NLRP3 inflammasome activity.

Autophagy has been reported to be involved in many aspects of innate and adaptive immunity. Manipulating autophagy is recognized as a promising therapeutic approach for treating immunological diseases, including allograft rejection, and graft-versus-host disease. However, whether autophagy was closely associated with the pathogenesis of corneal allograft rejection remains largely unknown. Here, we showed that rapamycin (RAPA)-induced autophagy alleviated corneal allograft rejection. By contrast, blocking autophagic activity using 3-methyladeine (3-MA) aggravated corneal transplantation rejection. Mechanistically, we revealed that the enhanced autophagic turnover by RAPA inhibited NLRP3 inflammasome activity through NLRP3 degradation. While blocking the fusion of autophagosomes with lysosomes by bafilomycin A1(BafA1), the reduced NLRP3 inflammasome activity induced by RAPA was significantly restored, with increased protein levels of NLRP3 and cleaved Casp-1(p10), as well as IL-1ß secretion. Moreover, we further revealed that pharmacologically blocking NLRP3 inflammasome signaling prolonged the survival of corneal allografts. Taken together, these findings underscored the critical roles of enhanced autophagy in treating corneal allograft rejection, which provided an alternative intervention strategy to control corneal transplantation rejection.

Monolith/Hydrogel composites as triamcinolone acetonide carriers for curing corneal neovascularization in mice by inhibiting the fibrinolytic system.

Corneal neovascularization is a serious corneal pathological change caused by various factors. The drug delivery system is of great significance for the effective treatment of corneal neovascularization. Herein, we developed and characterized a monolith/hydrogel composite as the triamcinolone acetonide (TA) carrier for curing corneal neovascularization. The composite was prepared by photo-initiated free radical polymerization of multi-methacrylate substituted dodecamine organic molecular cage and post-modified by the sequential photo-initiated free radical polymerization of acrylated gelatin. The globular morphology and structural property of as-prepared composites were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy and solid-state cross polarization magic angle spinning carbon-13 nuclear magnetic resonance. Then swelling ratio and the TA loading capacity were investigated then. Compared with gelatin hydrogel, the composites exhibited a decreased swelling ratio and an improved loading capacity. With good biocompatibility, the composite can sustainedly release TA for up to 28 days, and effectively inhibit corneal neovascularization with an alkali burn-induced corneal neovascularization model. Additionally, tandem mass tags-labeled quantitative proteomics were performed to identify differentially expressed proteins between vascularized and devascularized corneas. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the inhibition process could be primarily linked to the fibrinolytic system. These results demonstrated the potential of monolith/hydrogel composites as delivery systems in the therapy for biomedical diseases.

Deep Eutectic Solvents as Active Pharmaceutical Ingredient Delivery Systems in the Treatment of Metabolic Related Diseases.

Metabolic related diseases such as cancer, diabetes mellitus and atherosclerosis are major challenges for human health and safety worldwide due to their associations with high morbidity and mortality. It is of great significance to develop the effective active pharmaceutical ingredient (API) delivery systems for treatment of metabolic diseases. With their unique merits like easy preparation, high adjustability, low toxicity, low cost, satisfactory stability and biodegradation, deep eutectic solvents (DESs) are unarguably green and sustainable API delivery systems that have been developed to improve drug solubility and treat metabolic related diseases including cancer, diabetes mellitus and atherosclerosis. Many reports about DESs as API delivery systems in the therapy of cancer, diabetes mellitus and atherosclerosis exist but no systematic overview of these results is available, which motivated the current work.