Accelerated healing of intractable biofilm-infected diabetic wounds by trypsin-loaded quaternized chitosan hydrogels that disrupt extracellular polymeric substances and eradicate bacteria.

Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.

DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome-mediated cell-cell communication.

The involvement of DEAD-box helicase 55 (DDX55) in oncogenesis has been suggested, but its biological role in hepatocellular carcinoma (HCC) remains unknown. The present study verified the upregulation of DDX55 in HCC tissues compared with non-tumor controls. DDX55 displayed the highest prognostic values among the DEAD-box protein family for recurrence-free survival and overall survival of HCC patients. In addition, the effects of DDX55 in the promotion of HCC cell proliferation, migration, and invasion were determined ex vivo and in vivo. Mechanistically, we revealed that DDX55 could interact with BRD4 to form a transcriptional regulatory complex that positively regulated PIK3CA transcription. Following that, ß-catenin signaling was activated in a PI3K/Akt/GSK-3ß dependent manner, thus inducing cell cycle progression and epithelial-mesenchymal transition. Intriguingly, both DDX55 mRNA and protein were identified in the exosomes derived from HCC cells. Exosomal DDX55 was implicated in intercellular communication between HCC cells with high or low DDX55 levels and between HCC cells and endothelial cells, thereby promoting the malignant phenotype of HCC cells and angiogenesis. In conclusion, DDX55 may be a valuable prognostic biomarker and therapeutic target in HCC.