ABSTRACT
The skin secretion of tree frogs contains a vast array of bioactive chemicals for repelling predators, but their structural and functional diversity is not fully understood. Paxilline (PAX), a compound synthesized by Penicillium paxilli, has been known as a specific antagonist of large conductance Ca2+-activated K+ Channels (BKCa). Here, we report the presence of PAX in the secretions of tree frogs (Hyla japonica) and that this compound has a novel function of inhibiting the potassium channel subfamily K member 18 (KCNK18) channels of their predators. The PAX-induced KCNK18 inhibition is sufficient to evoke Ca2+ influx in charybdotoxin-insensitive DRG neurons of rats. By forming π-π stacking interactions, four phenylalanines located in the central pore of KCNK18 stabilize PAX to block the ion permeation. For PAX-mediated toxicity, our results from animal assays suggest that the inhibition of KCNK18 likely acts synergistically with that of BKCa to elicit tingling and buzzing sensations in predators or competitors. These results not only show the molecular mechanism of PAX-KCNK18 interaction, but also provide insights into the defensive effects of the enriched PAX.
Subject(s)
Anura , Indoles , Animals , Rats , Indoles/pharmacology , Potassium Channels/metabolismABSTRACT
The effect of weakly charged insoluble karaya gum (KG) on zein colloidal nanoparticles (ZKGPs) for stabilizing Pickering emulsions was investigated. Due to weak surface charge, KG could cover the surface of zein particles by hydrogen bonds and weak electrostatic interactions. With the increase in coverage, the zeta potential of ZKGPs changed from positive to negative values close to zero and the average particle size tended to become larger. The closest neutral wettability (89.85°) was achieved when the zein/KG mass ratio was 1:1. The samples prepared with high oil volume fraction (φ = 0.5-0.75) and high particle concentration (1.0-1.3 %, w/v) formed emulsion gels easily and showed higher storage stability. CLSM images also confirmed that ZKGPs could be distributed in the continuous phase to enhance the emulsion network structure. Consequently, weakly charged ZKGPs reduced the emulsification energy barrier and increased the coverage and steric hindrance of particles at the oil/water interface. These findings provide new ideas for the development of stable Pickering emulsions for application in food textural modification as well as encapsulation and delivery of bioactive substances.
Subject(s)
Nanoparticles , Zein , Zein/chemistry , Emulsions/chemistry , Karaya Gum , Nanoparticles/chemistry , Particle SizeABSTRACT
BACKGROUND: Insulin resistance, liver injury and dyslipidemia are reported in non-alcoholic fat liver disease (NAFLD) patients. Interleukin (IL)-38 may take part in the pathophysiology of insulin resistance. Nevertheless, the function of IL-38 in NAFLD is unknown. Herein, we determined whether serum IL-38 level might be utilised as a biochemical marker for diagnosing NAFLD. METHODS: NAFLD patients and healthy participants (n = 91 each) were enrolled. Circulating serum IL-38 levels were detected using enzyme-linked immunosorbent assay. Other metabolic and inflammatory indices related to NAFLD were also assessed. RESULTS: Patients with NAFLD had higher serum IL-38 levels than healthy individuals. Significantly higher serum IL-38 levels were found in patients with severe and moderate NAFLD than in patients with mild NAFLD. IL-38 showed a significant correlation with parameters of insulin resistance, inflammation, and liver enzyme in NAFLD cases. Anthropometric, insulin resistance, inflammatory parameters, lipids and frequency of NAFLD showed significant differences among the serum IL-38 level tertiles. Participants in the 2nd and 3rd tertiles of serum IL-38 levels had a greater risk of NAFLD than those in the 1st tertile. Furthermore, IL-38 ROC curve showed a high area under ROC with 0.861. CONCLUSIONS: It is possible for serum IL-38 to be a biomarker for NAFLD.
