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-QN...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)=2.64μmol/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.展开更多
Regenerative medicine and anti-aging research have made great strides at the molecular and cellular levels in dermatology and the medical aesthetic field,targeting potential treatments with skin therapeutic and interv...Regenerative medicine and anti-aging research have made great strides at the molecular and cellular levels in dermatology and the medical aesthetic field,targeting potential treatments with skin therapeutic and intervention pathways,which make it possible to develop effective skin regeneration and repair ingredients.With the rapid development of computational biology,bioinformatics as well as artificial intelligence(A.I.),the development of new ingredients for regenerative medicine has been greatly accelerated,and the success rate has been improved.Some application cases have appeared in topical skin regeneration and repair scenarios.This review will briefly introduce the application of bioactive peptides in skin repair and anti-aging as emerging ingredients in cosmeceutics and emphasize how A.I.based computational biology technology may accelerate the development of innovative peptide molecules and ultimately translate them into potential skin regenerative and anti-aging scenarios.Typically,two research routines have been summarized and current limitations as well as directions were discussed for border applications in future research.展开更多
基金supported by the National Natural Science Foundation of China(32301054,82404582,32360138,32060212)First-Class Discipline Team of Skin&Mucosal Regenerative Medicine of Kunming Medical University(2024XKTDTS10)+2 种基金Key Program of Yunnan Fundamental Research Project(202301AS070036)Open Research Fund of Yunnan Characteristic Plant Extraction Laboratory(YKKF2024003)Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation(202301AY070001-301,202401AY070001-028,202301AY070001-012,202401AY070001-068,202301AY070001-169)。
文摘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)=2.64μmol/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.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515030047)Zhejiang Provincial Department of Agriculture and Rural Affairs(2022SNJF078).
文摘Regenerative medicine and anti-aging research have made great strides at the molecular and cellular levels in dermatology and the medical aesthetic field,targeting potential treatments with skin therapeutic and intervention pathways,which make it possible to develop effective skin regeneration and repair ingredients.With the rapid development of computational biology,bioinformatics as well as artificial intelligence(A.I.),the development of new ingredients for regenerative medicine has been greatly accelerated,and the success rate has been improved.Some application cases have appeared in topical skin regeneration and repair scenarios.This review will briefly introduce the application of bioactive peptides in skin repair and anti-aging as emerging ingredients in cosmeceutics and emphasize how A.I.based computational biology technology may accelerate the development of innovative peptide molecules and ultimately translate them into potential skin regenerative and anti-aging scenarios.Typically,two research routines have been summarized and current limitations as well as directions were discussed for border applications in future research.
