RESUMO
BACKGROUND: In the development of liver fibrosis, activated hepatic stellate cells (HSCs) contribute to the synthesis and deposition of extracellular matrix (ECM) proteins. HSC activation is considered as a central driver of liver fibrosis. Recently, microRNAs (miRNAs) have been reported to act as key regulators in HSC activation. PURPOSE: Pinostilbene hydrate (PSH), a methylated derivative of resveratrol, has demonstrated anti-inflammatory, antioxidant and anti-tumour activities. However, the effects of PSH on HSC activation remain unclear. METHODS: The effects of PSH on HSC activation were examined. Moreover, the roles of WNT inhibitory factor 1 (WIF1) and miR-17-5p in the effects of PSH on HSC activation were examined. RESULTS: PSH induced a significant reduction in HSC proliferation. PSH also effectively inhibited HSC activation, with reduced α-SMA and collagen expression. Notably, it was found that Wnt/ß-catenin signalling was involved in the effects of PSH on HSC activation. PSH resulted in Wnt/ß-catenin signalling inactivation, with a reduction in TCF activity as well as ß-catenin nuclear translocation. Further studies showed that PSH inhibited Wnt/ß-catenin signalling via regulation of WIF1 and miR-17-5p. Reduced HSC activation caused by PSH could be restored by loss of WIF1 or miR-17-5p mimics. Luciferase reporter assays further confirmed that WIF1 was a target of miR-17-5p. CONCLUSION: PSH has a significant protective effect against HSC activation. In addition, we demonstrate that PSH enhances WIF1 expression and inhibits Wnt/ß-catenin signalling via miR-17-5p, contributing to the suppression of HSC activation.
Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , MicroRNAs/metabolismo , Estilbenos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Actinas/genética , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , beta Catenina/metabolismoRESUMO
Bacillus thuringiensis (Bt) can produce Cry proteins during the sporulation phase, and Cry protein is effective against lepidopteran, coleopteran, and dipteran insects and nematodes. However, Cry protein tends to be discharged into soil and nontarget plants through rainwater runoff, leading to reduced effective period toward target insects. In the present study, nano-Mg(OH)2 (magnesium hydroxide nanoparticles, MHNPs) were synthesized to control the loss of Cry1Ac protein and deliver protein to Helicoverpa armigera (Lepidoptera: Noctuidae). The results showed that Cry1Ac protein could be loaded onto MHNPs through electrostatic adsorption, and both MHNPs and Cry protein were stable during the adsorption process. Meanwhile, the Cry1Ac-loaded MHNPs could remain on the surface of cotton leaves, resulting in enhanced adhesion of Cry1Ac protein by 59.50% and increased pest mortality by 75.00%. Additionally, MHNPs could be slowly decomposed by acid medium and MHNPs showed no obvious influence on cotton, Bt, Escherichia coli, and H. armigera. Therefore, MHNPs could serve as an efficient nanocarrier for delivery of Cry1Ac protein and be used as a potential adjuvant for biopesticide in agricultural applications.