Nano Self-Assemblies of Caffeic Acid-Fibronectin Mimic a Peptide Conjugate for the Treatment of Corneal Epithelial Injury.

Rapid corneal re-epithelialization is important for corneal wound healing. Corneal epithelial cell motility and oxidative stress are important targets for therapeutic intervention. In this study, we covalently conjugated the antioxidant caffeic acid (CA) with a bioactive peptide sequence (PHSRN) to generate a CA-PHSRN amphiphile, which was formulated into nanoparticular eye drops with an average size of 43.21 ± 16 nm. CA-PHSRN caused minimal cytotoxicity against human corneal epithelial cells (HCECs) and RAW264.7 cells, exhibited an excellent free radical scavenging ability, and remarkably attenuated reactive oxygen species (ROS) levels in H2O2-stimulated HCECs. The antioxidant and anti-inflammatory activities of CA-PHSRN were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results show that CA-PHSRN treatment effectively prevented LPS-induced DNA damage and significantly reduced the levels of LPS-induced pro-inflammatory cytochemokines (i.e., iNOS, NO, TNF-α, IL-6, and COX-2) in a dose-dependent manner. Moreover, using a rabbit corneal epithelial ex vivo migration assay, we demonstrated that the proposed CA-PHSRN accelerated corneal epithelial cell migration and exhibited high ocular tolerance and ocular bioavailability after topical instillation. Taken together, the proposed CA-PHSRN nanoparticular eye drops are a promising therapeutic formulation for the treatment of corneal epithelial injury.

HMGB1: An overview of its roles in the pathogenesis of liver disease.

High-mobility group box 1 (HMGB1) is an abundant architectural chromosomal protein that has multiple biologic functions: gene transcription, DNA replication, DNA-damage repair, and cell signaling for inflammation. HMGB1 can be released passively by necrotic cells or secreted actively by activated immune cells into the extracellular milieu after injury. Extracellular HMGB1 acts as a damage-associated molecular pattern to initiate the innate inflammatory response to infection and injury by communicating with neighboring cells through binding to specific cell-surface receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE). Numerous studies have suggested HMGB1 to act as a key protein mediating the pathogenesis of chronic and acute liver diseases, including nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic ischemia/reperfusion injury. Here, we provide a detailed review that focuses on the role of HMGB1 and HMGB1-mediated inflammatory signaling pathways in the pathogenesis of liver diseases.