RESUMO
Wound dressings created using nanotechnology are known as suitable substrates to speed up the healing of both acute and chronic wounds. Therapeutic substances can be delivered using these materials. In this study, a hydrogel loaded with Cu (II) Schiff base 8-hydroxy quinoline complex (CuSQ) solid lipid nanoparticles (SLN) was formulated to investigate its wound healing potential in an excision wound healing model in rats. The CuSQ SLN were spherical shaped with sizes ranging from 111 to 202 nm and a polydispersity index (PDI) ranging from 0.43 to 0.76, encapsulation efficiency (EE) % between 85 and 88, and zeta potential (ZP) of -11.8 to -40 mV. The formulated hydrogel showed good homogeneity, good stability, and a pH of 6.4 which indicates no skin irritation and had no cytotoxicity on the human skin fibroblast (HSF) cell line. In the in vivo study, animals were placed in five groups: control, standard, plain hydrogel, low dose, and high dose of CuSQ hydrogel. Both doses of CuSQ showed significantly faster healing rates compared to standard and control rats. In addition, the histopathology study showed more collagen, improved angiogenesis, and intact re-epithelization with less inflammation. A significant increase in transforming growth factor-beta1 (TGF-ß1) level and increased immune expression of vascular endothelial growth factor (VEGF) by CuSQ treatment validates its role in collagen synthesis, proliferation of fibroblasts and enhancement of angiogenesis. Matrix metalloproteinase-9 (MMP-9) was found to be significantly reduced after CuSQ treatment. Immunohistochemistry of tumor necrosis factor alpha (TNF-α) revealed a marked decrease in inflammation. Thus, we concluded that CuSQ would be a beneficial drug for cutaneous wound healing since it effectively accelerated wound healing through regulation of various cytokines and growth factors.
RESUMO
OBJECTIVE: The purpose of the current study was to investigate the possible anti-tumor effect of miR-27a inhibitor in combination with Sorafenib (SOR) on cell proliferation and apoptosis of hepatocellular carcinoma cell lines. METHODS: Transient transfection by oligo-miR27a inhibitor (miR-27ai) was used in this study for targeting the oncogenic miR-27a in HepG2 and Huh7 cells followed by SOR treatment. Cell viability was measured using SRB assay. The cell cycle and apoptosis were assessed by flow cytometry assay. Moreover, the level of oncogenic miR-27a was evaluated in 19 tissues of primary HCC patients as well as cell lines using qRT-PCR assay. Finally, caspase-3 activity was determined using ELISA assay. RESULTS: Significant up-regulation of miR-27a expression was reported in HCC patients confirming its oncogenic role. Treatment of cells with SOR following transfection with miR-27ai declined cell viability significantly compared with either control or single agent treatment (p≤0.05). Highly significant decreasing in the number of cell in S-phase associated with increasing in G0-phase was also observed. Furthermore, apoptotic rate was highly significantly increased for transfected/SOR treated cells (p≤0.01). Finally, combination treatment demonstrated a significant elevation of caspase-3 activity level in both cell lines examined. CONCLUSION: The present data demonstrated targeting miR-27a enhances the anti-tumor effect of SOR in HCC cell lines considering as one of the promising therapeutic targets for advanced HCC management.
