<div>Abstract<p>Scutellarin is a flavonoid compound that is found in <i>Scutellaria barbata</i>. It has been reported to exhibit anticancer and anti-inflammation activities. However, the anticancer properties of scutellarin and its molecular targets have not been investigated in esophageal squamous cell carcinoma (ESCC). In the current study, we report that scutellarin is a potential AKT inhibitor that suppresses patient-derived xenograft ESCC tumor growth. To identify possible molecular targets of scutellarin, potential candidate proteins were screened by an <i>in vitro</i> kinase assay and Western blotting. We found that scutellarin directly binds to the AKT1/2 proteins and inhibits activities of AKT1/2 <i>in vitro</i>. The AKT protein is activated in ESCC tissues and knockdown of AKT significantly suppresses growth of ESCC cells. Scutellarin significantly inhibits anchorage-dependent and independent cell growth and induces G<sub>2</sub> phase cell-cycle arrest in ESCC cells. The inhibition of cell growth by scutellarin is dependent on the expression of the AKT protein. Notably, scutellarin strongly suppresses patient-derived xenograft ESCC tumor growth in an <i>in vivo</i> mouse model. Taken together, our data suggest that scutellarin is a novel AKT inhibitor that may prevent progression of ESCC.</p></div>
Nanoparticles (NPs) have shown great promise as intracellular imaging probes or nanocarriers and are increasingly being used in biomedical applications. A detailed understanding of how NPs get "in and out" of cells is important for developing new nanomaterials with improved selectivity and less cytotoxicity. Both physical and chemical characteristics have been proven to regulate the cellular uptake of NPs. However, the exocytosis process and its regulation are less explored. Herein, we investigated the size-regulated endocytosis and exocytosis of carboxylated polystyrene (PS) NPs. PS NPs with a smaller size were endocytosed mainly through the clathrin-dependent pathway, whereas PS NPs with a larger size preferred caveolae-mediated endocytosis. Furthermore, our results revealed exocytosis of larger PS NPs and tracked the dynamic process at the single-particle level. These results indicate that particle size is a key factor for the regulation of intracellular trafficking of NPs and provide new insight into the development of more effective cellular nanocarriers.
Combination treatment through simultaneous delivery of anticancer drugs and gene with nano-formulation has been demonstrated to be an elegant and efficient approach for colorectal cancer therapy. Recently, sorafenib being studied in combination therapy in colorectal cancer (CRC) attracted attention of researchers. On the basis of our previous study, pigment epithelium-derived factor (PEDF) loaded nanoparticles showed good effect on CRC in vitro and in vivo. Herein, we designed a combination therapy for sorafenib (Sora), a multi-kinase inhibitor and PEDF, a powerful antiangiogenic gene, in a nano-formulation aimed to increase anti-tumor effect on CRC for the first time. Sora and PEDF were simultaneously encapsulated in PEG-PLGA based nanoparticles by a modified double-emulsion solvent evaporation method. The obtained co-encapsulated nanoparticles ([email protected]) showed high entrapment efficiency of both Sora and PEDF — and exhibited a uniform spherical morphology. The release profiles of Sora and PEDF were in a sustained manner. The most effective tumor growth inhibition in the C26 cells and C26-bearing mice was observed in the [email protected] in comparison with none-drug nanoparticles, free Sora, mono-drug nanoparticles (Sora-NPs and PEDF-NPs) and the mixture of Sora-NPs and equivalent PEDF-NPs (Mix-NPs). More importantly, [email protected] showed lower toxicity than free Sora in mice according to the acute toxicity test. The serologic biochemical analysis and mice body weight during therapeutic period revealed that [email protected] had no obvious toxicity. All the data demonstrated that the simultaneously loaded nanoparticles with multi-kinase inhibitor and anti-angiogenic gene might be one of the most potential formulations in the treatment of colorectal carcinoma in clinic and worthy of further investigation.
Cholera toxin B-subunit (CTxB) has emerged as one of the most widely utilized tools in membrane biology and biophysics. CTxB is a homopentameric stable protein that binds tightly to up to five GM1 glycosphingolipids. This provides a robust and tractable model for exploring membrane structure and its dynamics including vesicular trafficking and nanodomain assembly. Here, we review important advances in these fields enabled by use of CTxB and its lipid receptor GM1.
A novel hybrid hydrogel was prepared and investigated based on silkworm silk fibroin and poly( N ‐isopropylacrylamide) (PNIPAAm). PNIPAAm was introduced to silk fibroin, the resultant composite hydrogel was examined, and freeze‐dried SF/PNIPAAm scaffold was analyzed using LB‐550 dynamic light scattering particle‐size analyzer, circular dichroism (CD), and scanning electron microscopy (SEM). Our results suggested that the hybrid hydrogels owned the porous sponge‐like structures, and the gelation time of SF/PNIPAAm hybrids decreased with an increase in temperature and concentration of each polymer. Results of rheological analysis suggested that the rheological property of resultant SF/PNIPAAm gel depended on the concentration combinations as well as the aging time, which elapsed after mixing the two polymers. Results of CD spectra demonstrated that pH showed little influence on the secondary structure of silk fibroin, and significant changes of G ′ , G ′ ′ , and G* as surrounding increase temperature above the lower critical solution temperature (LCST).
pH control of suspensions of titania coated with silica and alumina has been investigated. The experimental results show that SiO2 and Al2O3 can form a dense film coating on the titania particle surfaces,and the film became thicker as the amount of coating material was increased. According to GB/T 1706—2006,the samples were formed into aqueous suspensions at a concentration of 10% by weight. pH measurements showed that the suspension of titania coated with SiO2 is alkaline,and the pH increases with coating amount up to pH 9.7. In contrast,the suspension of titania coated with Al2O3 is acid,and the pH decreases with coating amount down to pH 4.4. The zeta potential was also affected by the surface coating in a similar way to the pH. The pH of the suspension can be controlled effectively by a thin coating of alumina on silica-coated particles,and a thin coating of silica on alumina-coated particles.
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