Treating Autoimmune Diseases by Targeting IL-23 with Gene-Silencing Pyrrole-Imidazole Polyamide.

Autoimmune diseases are a physiological state that immune responses are directed against and damage the body's own tissues. Numerous studies have demonstrated promising therapeutic effects in certain autoimmune diseases by targeting IL-23/IL-17 axis, mostly through using Abs against IL-23 or IL-17A. Pyrrole-imidazole polyamides are nuclease-resistant compounds that inhibit gene expression through binding to the minor groove of DNA. To develop a novel gene-silencing agent that targets IL-23/IL-17 axis, we designed polyamide that specifically binds to the transcription factor c-Rel-binding site located in the promoter of IL-23p19 subunit. Our study showed that this polyamide is capable of entering into nucleus with high efficiency in dendritic cells and macrophage. In addition, it prevented the binding of c-Rel to the promoter of IL-23p19 in vivo and specifically inhibited the expression of IL-23. More importantly, we demonstrated that this polyamide is therapeutically effective using both the imiquimod-induced psoriasis and experimental autoimmune uveitis mouse models. Taken together, these results indicate that pyrrole-imidazole polyamide targeting IL-23p19 could be a novel and feasible therapeutic strategy for patients with autoimmune diseases.

The dual function of calcium ion in fruit edible coating: Regulating polymer internal crosslinking state and improving fruit postharvest quality.

The edible coating is proved to be a convenient approach for fruit preservation. Among these published explorations, naturally sourced macromolecules and green crosslinking strategies gain attention. This work centers on edible coatings containing Ca2+ as crosslinker for the first time, delving into crosslinking mechanisms, include alginate, chitosan, Aloe vera gel, gums, etc. Additionally, the crucial functions of Ca2+ in fruit's quality control are also elaborated in-depth, involving cell wall, calmodulin, antioxidant, etc. Through a comprehensive review, it becomes evident that Ca2+ plays a dual role in fruit edible coating. Specifically, Ca2+ constructs a three-dimensional dense network structure with polymers through ionic bonding. Moreover, Ca2+ acts directly with cell wall to maintain fruit firmness and serve as a second messenger to participate secondary physiological metabolism. In brief, coatings containing Ca2+ present remarkable effects in preserving fruit and this work may provide guidance for Ca2+ related fruit preservation coatings.

Melatonin treatment delays the softening of blueberry fruit by modulating cuticular wax metabolism and reducing cell wall degradation.

The effects of postharvest melatonin (MT) treatment on cuticular wax and cell wall metabolism in blueberry fruit (Vaccinium spp.) were evaluated. The results revealed that MT treatment maintained the cuticular wax rod-like structure and delayed wax degradation. The gas chromatography-mass spectrometry analysis results revealed that MT application changed the cuticular wax composition in blueberries, and 25 metabolic components were screened. The metabolic regulation of wax quality in blueberry fruit may therefore be influenced by MT. Additionally, MT slowed down pectin and cellulose degradation by reducing the activities of cell wall degrading enzymes like pectin methyl esterase polygalacturonase, ß-galactosidase, and cellulose in the later stages of storage. It also downregulated the transcriptional expression of related genes like VcPE, VcPG, VcBG6, and VcGAL1. Thus, MT prevented softening and senescence by postponing the degradation of the cell wall in postharvest blueberry fruit.

Development of bio-based PLA/cellulose antibacterial packaging and its application for the storage of shiitake mushroom.

This study presents the extraction of cellulose from water bamboo byproducts to prepare polylactic acid (PLA)/cellulose antibacterial packaging material. The cellulose was modified using a silane coupling agent, which improved the interfacial compatibility between cellulose and PLA. Upon coating the PLA onto the modified cellulose sheet, the water contact angle of the composite material increased from 11.42° to 132.12° and the water absorption rate decreased from 182.52% to 55.71%, which improved the water resistance performance of the material. The addition of cinnamaldehyde in the PLA layer imparted antibacterial activity to the PLA/cellulose packaging material. This packaging material effectively inhibited the mycelial growth and spore germination of Aspergillus niger and Trichoderma harzianum isolated from shiitake mushroom. Additionally, the study investigated the effects of the composite on the postharvest quality of shiitake mushroom. Overall, the packaging material contributed to shiitake mushroom storage and can be applied to other perishable food products.

Amphiphilic prodrug-decorated graphene oxide as a multi-functional drug delivery system for efficient cancer therapy.

Graphene oxide (GO) has shown great potential in drug delivery. However, the aqueous stability, non-specific drug release and slow release rate are major problems of the GO-based drug delivery system. Herein, we for the first time integrate the dispersant, stabilizing agent and active targeting carrier into a novel drug delivery system based on GO/PP-SS-DOX nanohybrids. The redox-sensitive PP-SS-DOX prodrug was obtained by conjugating mPEG-PLGA (PP) with doxorubicin (DOX) via disulfide bond. PEG-FA provided active targeting property for the constructed drug delivery system, GO/PP-SS-DOX/PEG-FA. In this demonstrated system, PP-SS-DOX markedly increases the stability in physiological solutions of GO and guarantees the DOX release in the reductive environment (cancerous cells). And PEG-FA helps target to cancerous tissues and induces FR-mediated endocytosis. In vitro drug release exhibited the obvious reductive sensitivity and the cumulative release amount was up to 90%, while 40% in previous reports within 72 h. The in vitro cytotoxicity of targeting nanohybrids was significantly cytotoxic than that of non-targeting nanohybrids. In vivo results displayed that the as-prepared targeting nanohybrids showed efficacious antitumor effect while it had nearly no systemic adverse toxicity on B16 tumor-bearing mice. Therefore, the in vitro and in vivo results indicate that our constructed GO/PP-SS-DOX/PEG-FA drug delivery system is a promising carrier in cancer therapy.