Bruton's tyrosine kinase ablation inhibits B cell responses and antibody production for the prevention of chronic rejection in cardiac transplantation.

Chronic rejection is the primary cause of late allograft failure, however, the current treatments for chronic rejection have not yielded desirable therapeutic effects. B cell activation and donor-specific antibody (DSA) production are the primary factors leading to chronic rejection. Bruton's tyrosine kinase (BTK) plays a key role in the activation and differentiation of B cells and in antibody production. This study investigated the efficacy of blocking BTK signalling in the prevention of chronic rejection. BTK signalling was blocked using the BTK inhibitor ibrutinib and gene knockout. In vitro assays were conducted to examine the consequences and underlying mechanisms of BTK blockade in regards to B cell activation, differentiation, and antibody secretion. Additionally, we established a cardiac transplantation mouse model of chronic rejection to explore the preventive effects and mechanisms of BTK ablation on chronic rejection. Ablating BTK signalling in vitro resulted in the inhibition of B cell activation, differentiation, and antibody production. In vivo experiments provided evidence that ablating BTK signalling alleviated chronic rejection, leading to reduced damage in myocardial tissue, neointimal hyperplasia, interstitial fibrosis, inflammatory cell infiltration, and C4d deposition. Allograft survival was prolonged, and B cell responses and DSA production were inhibited as a result. We confirmed that ablation of BTK signalling inhibited B cell response by blocking downstream PLCγ2 phosphorylation and inhibiting the NF-κB, NFAT, and ERK pathways. Our findings demonstrated that ablation of BTK signalling inhibited B cell activation and differentiation, reduced DSA production, and effectively prevented chronic rejection.

Electrical and visible light dual-responsive ZnO nanocomposite with multiple wound healing capability.

The healing process of open wounds is a competition between cells and bacteria. Therefore, a strategy that can quickly remove bacteria and promote cell proliferation to accelerate wound healing is urgently needed. Inspired by photoelectric synergy tactics, we improved both the optical and electrical response of zinc oxide (ZnO) through the modification of polydopamine (PDA) and reduced graphene oxide (rGO), thus obtaining a ZnO composite named PDA-rGO-ZnO (PrZ). Combined with the photoelectric double stimulation, the sterilization target could be completed from multiple physical levels simultaneously. More importantly, the band gap of ZnO was considerably narrowed by PDA encapsulation. The encapsulated ZnO thus could be effectively excited by pure yellow light (YL) with a moderate long wavelength, which fundamentally improved its safety in exerting photocatalytic antibacterial properties. In addition, we found that electrical stimulation (ES) could not only help to clear bacteria, but also facilitate the formation of new blood vessels. Animal experiments further showed that PrZ efficaciously regulated the immune response around the wound surface, promoted cell proliferation and the formation of collagen fibers, thereby accelerating wound healing.