Cy RL-QN15

Skin photoaging, a process with substantial physical and psychological impacts, is also a recognized risk factor for skin cancer. Despite advancements in dermatological research, effective prevention and reversal of photoaging remain challenging. This study investigated the efficacy of Cy_RL-QN15, an optimized variant derived from the RL-QN15 peptide, in mitigating ultraviolet B (UVB)-induced skin photoaging in mice. Results showed that Cy_RL-QN15 promoted skin barrier repair and exhibited antioxidant and anti-apoptotic properties. Mechanistically, these effects were mediated by activating the downstream Wnt/β-catenin signaling pathway. Notably, the therapeutic efficacy of Cy_RL-QN15 was diminished by using the inhibitor MSAB, suggesting a crucial role for the β-catenin signaling pathway. Furthermore, Cy_RL-QN15 may exert its effects by binding to the Frizzled-8 receptor on the human keratinocyte (HaCaT) cell membranes. This study is the first to identify the role of β-catenin regulation in skin barrier dysfunction during photoaging, establishing a potential therapeutic foundation for targeting Cy_RL-QN15 to combat skin photoaging.

Oral ulcers (OUs) are among the most common lesions of the oral mucosa, typically associated with pain and burning sensations, and remain clinically challenging due to the scarcity of effective treatment options. Cy _RL-QN15, a novel ultra-short cyclic heptapeptide recently shown to promote skin repair, diabetic wound healing, and follicle neogenesis, was evaluated for its therapeutic potential in mucosal repair. Using a rat OU model and a primary oral epithelial cell inflammation model, Cy _RL-QN15 significantly accelerated wound closure through coordinated modulation of immune-epithelial crosstalk, including suppression of inflammatory cytokine release from macrophages and neutrophils, reduction of pro-inflammatory factor secretion by oral epithelial cells, and enhancement of their proliferation and migration. Mechanistic studies employing alanine scanning mutagenesis and microscale thermophoresis revealed that Cy _RL-QN15 directly interacted with Toll-like receptor 4 (TLR4) via a methionine-dependent binding interface (K _d=2.64 µmol/L), thereby inhibiting downstream MyD88/NF-κB signaling. As the first ultra-short cyclic heptapeptide identified to antagonize TLR4, Cy _RL-QN15 represents a mechanistically distinct immunomodulatory scaffold that restores mucosal homeostasis and offers a promising therapeutic candidate for TLR4-based OU intervention.