miR-27b-3p is Involved in Doxorubicin Resistance of Human Anaplastic Thyroid Cancer Cells via Targeting Peroxisome Proliferator-Activated Receptor Gamma.

Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumours. To investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells. Targeted inhibition of miR-27b can increase the sensitivity of SW1736/Dox and 8305C/Dox cells. Bioinformatics analysis revealed that miR-27b can directly target peroxisome proliferator-activated receptor gamma (PPARγ) within the 3' untranslated region (UTR). This was proved by the results that miR-27b-3p down-regulated the protein and mRNA levels of PPARγ. While the mutant in the core binding sites of PPARγ abolished miR-27b-3p-induced down-regulation of luciferase activity. Over-expression of PPARγ can increase the Dox sensitivity of SW1736/Dox and 8305C/Dox cells. Basic fibroblast growth factor (bFGF) might be involved in miR-27b-3p/PPARγ-regulated Dox resistance of ATC cells. The activation of p65 nuclear factor-κB (NF-κB) regulated the up-regulation of miR-27b-3p in Dox-resistant ATC cells. Collectively, our data revealed that miR-27b-3p/PPARγ is involved in the Dox resistance of human ATC cells. It suggested that targeted inhibition of miR-27b-3p might be helpful to overcome the drug resistance of ATC cells.

Induction of apoptosis and autophagy in metastatic thyroid cancer cells by valproic acid (VPA).

The present study investigated the effect of valproic acid (VPA) on the inhibition of RET signaling and induction of apoptosis in human thyroid carcinoma cells. VPA inhibited the viability of ARO and WRO cells and also inhibited cyclin D1 and caused caspase-3 cleavage. VPA decreased the level of RET protein and blocked the activation of RET downstream targets including phosphorylated ERK, phosphorylated AKT, and p70S6K/pS6. VPA induced metabolic stress, activated AMP-activated protein kinase and increased autophagic flux. Pharmacological inhibition of autophagy (chloroquine) augmented VPA-inducible cytotoxicity, suggesting that autophagy was protective in VPA-treated cells. VPA has a wide spectrum of activity against human thyroid carcinoma cells, and its cytotoxicity can be augmented by inhibiting autophagy. Expression of VPA molecular targets in metastatic human thyroid carcinoma cells suggests that VPA has a potential to become a thyroid cancer therapeutic agent.

[In situ rat intestine absorption of paclitaxel-loaded solid lipid nanoparticles modified with cell-penetrating peptides].

To investigate the rat intestinal absorption of stearic acid-octaarginine (SA-R8) modified solid lipid nanoparticles containing paclitaxel (SA-R8-PTX-SLN), compared with the commercially available preparation of PTX (Taxol) and PTX-loaded solid lipid nanoparticles (PTX-SLN), the in situ intestinal absorption of SA-R8-PTX-SLN was investigated by means of single-pass rat intestinal perfusion technique. The absorptions of the preparations were investigated at different intestinal segments, different drug concentrations and in the presence of P-glycoprotein inhibitor (verapamil). The results showed that PTX could be absorbed at each intestinal segment and the three preparations all showed maximum absorptions at the duodenum. The cumulative absorptions of three preparations at each intestinal segment appeared SA-R8-PTX-SLN > PTX-SLN > Taxol (P < 0.05). SA-R8-PTX-SLN showed a liner absorption manner at the duodenum in the examined drug concentration range. The cumulative absorptions of Taxol and PTX-SLN were significantly promoted after the addition of P-glycoprotein inhibitor (verapamil) into the preparation (P < 0.05), but absorption of SA-R8-PTX-SLN existed no significantly difference compared with the preparation without verapamil (P > 0.05). SA-R8 and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.

Cell uptake of paclitaxel solid lipid nanoparticles modified by cell-penetrating peptides in A549 cells.

The aim of this study was to investigate the cytotoxicity of paclitaxel solid lipid nanoparticles (SLN) modified with stearic acid octaarginine (SA-R8-PTX-SLN) as well as the cellular uptake of coumarin-6-loaded SLN modified with SA-R8 (SA-R8-C6-SLN) in human lung cancer cells, A549. SLN were prepared using a film dispersion method; and then their particle size, zeta potential, morphology, bound efficiency of SAR8, drug loading efficiency, and in vitro release were characterized. SA-R8-PTX-SLN and SA-R8-C6-SLN were incubated with A549 cells to measure their cytotoxicity and cellular uptake, respectively. The results indicated that the cytotoxicity of SA-R8-PTX-SLN was enhanced significantly with the increasing amount of SA-R8 and the cellular uptakes of SLN increased with the incubated concentrations and the incubated time of SLN. In contrast, SA-R8-SLN could significantly enhance the cellular uptake of SLN and the cytotoxicity of PTX in A549 cells. These in vitro results suggest that SA-R8-SLN could be proposed as alternative drug delivery system.

[Influence of dredging on sediment resuspension and phosphorus transfer in lake: a simulation study].

A simulated experiment was conducted to investigate the impacts of sediment dredging on sediment resuspension and phosphorus transfer in the summer and winter seasons under the common wind-wave disturbance, and the contaminated sediment used in this study was from Meiliang Bay, Taihu lake. The result showed that 20 cm dredging could effectively inhibit the sediment resuspension in study area, dredging in winter has a better effect than that in summer, and the higher values of the total suspended solid (TSS) in undredged and dredged water column during the process of wind wave disturbance were 7.0 and 2.2, 24.3 and 6.4 times higher than the initial value in summer and winter simulation respectively. The paired-samples t-test result demonstrated that total phosphorus (TP) and phosphate (PO4(3-)-P) loading positively correlated to TSS content in dredged (P<0.01) and undredged water column (P<0.05), which proved that internal phosphorus fulminating release induced by wind-wave disturbance would significantly increase the TP and PO4(3-)-P loading in the water column. The effect of dredging conducted in summer on the TP and PO4(3)-P loading in the water column was negative, but not for winter dredging (P<0.01). The pore water dissolved reactive phosphorus (DRP) profile at water-sediment interface in summer simulation was also investigated by diffusive gradients in thin films (DGT) technique. Diffusion layer of the DRP profile in undredged sediment was wider than that in dredged sediment. However, the DRP diffusion potential in dredged sediment was greater than that in undredged sediment, showing that dredging can effectively reduce the risk of the DRP potential release in dredged pore water, but also would induce the DRP fulminating release in the short time under hydrodynamic action. Generally, dredging was usually deployed during the summer and the autumn. Considering Taihu Lake is a large, shallow, eutrophic lake and the contaminant distribution is spatially heterogeneous, it is vital to determine the optimal time, depth and scope of dredging.

Solid lipid nanoparticles modified with stearic acid-octaarginine for oral administration of insulin.

The aim of this study was to design and characterize solid lipid nanoparticles (SLNs) modified with stearic acid-octaarginine (SA-R8) as carriers for oral administration of insulin (SA-R8-Ins-SLNs). The SLNs were prepared by spontaneous emulsion solvent diffusion methods. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the SA-R8-Ins-SLNs were 162 nm, 29.87 mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed dramatically, from -32.13 mV to 29.87 mV, by binding the positively charged SA-R8. Morphological studies of SA-R8-Ins-SLNs using transmission electron microscopy showed that they were spherical. In vitro, a degradation experiment by enzymes showed that SLNs and SA-R8 could partially protect insulin from proteolysis. Compared to the insulin solution, the SA-R8-Ins-SLNs increased the Caco-2 cell's internalization by up to 18.44 times. In the in vivo studies, a significant hypoglycemic effect in diabetic rats over controls was obtained, with a SA-R8-Ins-SLN pharmacological availability value of 13.86 ± 0.79. These results demonstrate that SA-R8-modified SLNs promote the oral absorption of insulin.

[Cadmium and zinc absorption and distribution in various tree species in a mining area].

The study on the characteristics of cadmium (Cd) and zinc (Zn) absorption and distribution in 11 tree species in a mining area of Nanjing showed that the absorption and accumulation of test heavy metals differed with tree species, their organs, and heavy metals themselves. Among the test tree species, Viburnum awabuki had the highest Cd absorption, accumulation, and translocation rates, which could be used for the remediation of polluted soils via phytoextraction. Cd was mainly accumulated in tree roots, and its accumulation in tree organs was generally in the order of root > leaf and shoot > bark > stem. Zn was generally accumulated in above-ground part, such as in leaf and shoot, but not in root. For the test 11 tree species, the accumulation coefficients of Cd and Zn were all less than 0.2, while the translocation coefficients differed markedly, with that of Zn being higher than that of Cd in general.