The mechanisms of melanogenesis inhibition by glabridin:molecular docking,PKA/MITF and MAPK/MITF pathways

Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.

Geomorphology and sediment dynamics of the Liyashan oyster reefs,Jiangsu Coast,China

Oyster reefs and their spatial patterns are deemed to change the local hydrodynamic condition and exert profound impacts on the grain size,concentration and transportation of suspended sediments.Meanwhile,high suspended sediment concentration often results in excess mortality among oysters.Oyster reefs are rare and vital ecosystem in Liyashan national marine park,Jiangsu Coast,China.However,urgent conservation efforts should be made on account of the drastic reduction in reef areas.To investigate the sediment dynamics and the geomorphology,two tripod observation systems were deployed and UAV aerial surveys with elevation measurement using Real Time Kinematic(RTK)were also carried out.High mud content(60%)was found in the bed sediment at the reef ridge,causing much lower drag coefficient than other recorded values of living oyster reefs,indicating the death of oysters and the degradation of reefs in Liyashan.Ridgelines of the string reefs at 45°to the current direction and high suspended sediment concentration in the water body(50–370 mg/L)that exceeds the threshold(200 mg/L),which would affect nutrient uptake efficiency and further result in gill saturation,decrease of clearance rate and associated deposition,were probably crucial causes of the death of oysters.The findings are useful for restoring natural oyster reefs and designing artificial reefs for nature-based coastal defense.

ROS‑Scavenging Electroactive Polyphosphazene‑Based Core–Shell Nanofibers for Bone Regeneration

Bone defects are always accompanied by inflammation due to excessive reactive oxygen species(ROS)in injured regions,which greatly impedes the regeneration of bone tissues.Although many conductive polymers have been developed to scavenge ROS,they are typically non-degradable under physiological conditions,making them unsuitable for in vivo applications.Biodegradable polyorganophosphazenes(POPPs)may serve as potent ROS-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization.Herein,a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid)(PLGA)in regenerating bone tissues.To conduct in vitro and in vivo evaluations,three kinds of electrospun nanofibrous meshes were prepared:PLGA,PLGA/PATGP blend,and PLGA/PATGP core–shell nanofibers.Among them,PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ROS,promoting osteogenic differentiation,and accelerating neo-bone formation.The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix.Therefore,the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering.Additionally,the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials,without phase separation or difficulty of increasing the molecular weights of POPPs.

Synthesis and anticancer activity containing benzyl piperidone study of curcumin-related compounds

采用氮烷基化、羟基保护、醛酮缩合三步反应合成了16个新型单羰基姜黄素类似物,结构经质谱、核磁共振氢谱和共振碳谱等手段进行确认。并采用MTT染色法体外检测所合成的16个单羰基姜黄素类似物对人肺癌细胞H1299、结肠癌细胞HT-29、人胰腺癌细胞Bx PC-3和人前列腺癌细胞PC-3的抗癌活性。半数抑制浓度IC50值结果显示:所合成的16个姜黄素类似物对四种细胞均有较强的抑制作用,其中化合物A1和B3在四种细胞中的半数抑制浓度IC50均在1μmol/L以下。