Purified vitexin compound 1 (VB1), a novel lignanoid isolated from the seeds of the Chinese herb Vitex negundo, has strong antioxidant abilities and broad antitumor activities. However, little is known about its anti-photoaging effect on the skin and the underlying mechanism. Here, we demonstrated that VB1 significantly attenuates ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs), as evidenced by senescence-associated β-gal staining, MTT assays, and western blot analysis of the expression of p16 and matrix metalloproteinase-1 (MMP-1). Furthermore, mass spectrometry revealed that VB1 could directly bind to Mitogen-Activated Protein Kinase 1 (MAPK1). Molecular docking and molecular dynamics simulation methods confirmed the mass spectroscopy results and predicted six possible binding amino acids of MAPK1 that most likely interacted with VB1. Subsequent immunoprecipitation analysis, including different MAPK1 mutants, revealed that VB1 directly interacted with the residues, glutamic acid 58 (E58) and arginine 65 (R65) of MAPK1, leading to the partial reversal of UVA-induced senescence in HEK293T cells. Finally, we demonstrated that the topical application of VB1 to the skin of mice significantly reduced photoaging phenotypes in vivo. Collectively, these data demonstrated that VB1 reduces UVA-induced senescence by targeting MAPK1 and alleviates skin photoaging in mice, suggesting that VB1 may be applicable for the prevention and treatment of skin photoaging.

Background: The role of aberrant DNA methylation in allopurinol-induced severe cutaneous adverse reactions (SCARs) is incompletely understood. To fill the gap, we analyze the DNA methylation profiling in allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients and identify the DNA methylation signature for predisposing allopurinol hypersensitivity. Methods: Genome-scale methylation analysis was conducted using the Illumina^® HumanMethylation450 BeadChip. Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to analyze the data. Results: A total of 21,497 annotated promoter regions were analyzed. Ten modules were identified between allopurinol hypersensitivity and tolerance, with turquoise and yellow modules being the most significant correlation. ATG13, EPM2AIP1, and SRSF11 were the top three hub genes in the turquoise module. MIR412, MIR369, and MIR409 were the top three hub genes in the yellow module. Gene Ontology (GO) analysis revealed that the turquoise module was related to the metabolic process in intracellular organelles and the binding of various compounds, proteins, or nucleotides. The yellow module, however, was related to stimulus sensory perception in cytoskeletal elements and the activity of the receptor or transducer. Conclusion: DNA methylation plays a vital role in allopurinol-induced SCARs. DNA methylation profiling of SJS/TEN is significantly related to autophagy and microRNAs (miRNAs).

Introduction: Impaired wound healing leads to compromised cutaneous barrier and dysfunction, which still remains a challenging problem. However, safe and efficient materials and treatments for promoting wound healing are still lacking. Metal nanoparticles especially palladium nanoparticles (Pd NPs) have attracted tremendous interests in medical application in recent years, due to its unique physicochemical properties and biological inertness. Thereinto, Pd icosahedra nanoparticles (Pd Icos NPs) and Pd octahedra nanoparticles (Pd Oct NPs) have superior catalytic activity compared to other shapes but the application in skin wound healing have not been studied and reported. Methods: Pd Oct NPs and Pd Icos NPs were synthesized by seed-mediated growth method and one-step synthesis method and characterized by series physical chemical assays. The acute full-thickness skin excision wound mouse model was used to access the wound healing potential and screen out the effective materials—Pd Icos NPs. Next evaluate the biotoxicity and safety of Pd Icos NPs and both in HaCaT cells and in vivo. Further examine related molecules expression by RT-qPCR and WB in HaCaT cells and wound tissues with Pd Icos treatment. Then knockout the related molecules both in HaCaT cells and in vivo to validate the molecular mechanism of these molecules in the phenotype of wound healing promoted by Pd Icos NPs. Results: Pd Icos NPs with surface and tensile strain rather than Pd Oct NPs can promote skin wound healing. Pd Icos NPs upregulates the expression of HBEGF by promoting the production of transcription factor SP1, and contributes to keratinocytes proliferation and accelerating acute full-thickness skin wound healing. Discussion: Pd Icos NPs represent an effective and safe material for skin wound healing, suggesting a potential novel therapeutic strategy.