No abstract

Doxorubicin is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. Autophagy, a conserved catabolic process for cellular self-protection and adaptation to the changing environment, is regarded as a potential clinical target to overcome doxorubicin resistance. In this study, the potential role of miR-223 in modulating doxorubicin-induced autophagy and sensitivity were evaluated in four transfected human HCC cell lines, and the in vivo relevance was assessed using a mouse xenograft model of HCC. We found that the well-defined miR-223 is expressed at low levels in doxorubicin treated HCC cells and that miR-223 overexpression inhibits the doxorubicin-induced autophagy that contributes to chemoresistance. Blockade of autophagic flux by chloroquine resulted in the failure of miR-223 inhibitor to suppress doxorubicin sensitivity of HCC cells. We further identified FOXO3a as a direct downstream target of miR-223 and primary mediator of the regulatory effect of miR-223 on doxorubicin-induced autophagy and chemoresistance in HCC cells. Finally, we confirmed the enhancement of doxorubicin sensitivity by agomiR-223 in xenograft models of HCC. These findings establish a novel miRNA-based approach for autophagy interference to reverse doxorubicin resistance in future chemotherapy regimens against human HCC.

The significant risk factors for IAH in patients with SAP include 24 h fluid balance (first day), number of fluid collections, and serum calcium level. Additionally, IAH is associated with extremely poor prognosis, evidenced by high rates of mortality, morbidity, and the need for invasive interventions.

Surface plasmons that propagate along cylindrical metal/dielectric interfaces in annular apertures in metal films, called cylindrical surface plasmons (CSPs), exhibit attractive optical characteristics. However, it is challenging to fabricate these nanocoaxial structures. Here, we demonstrate a practical low-cost route to manufacture highly ordered, large-area annular cavity arrays (ACAs) that can support CSPs with great tunability. By employing a sol-gel coassembly method, reactive ion etching and metal sputtering techniques, regular, highly ordered ACAs in square-centimeter-scale with a gap width tunable in the range of several to hundreds of nanometers have been produced with good reproducibility. Ag ACAs with a gap width of 12 nm and a gap height of 635 nm are demonstrated. By finite-difference time-domain simulation, we confirm that the pronounced dips in the reflectance spectra of ACAs are attributable to CSP resonances excited in the annular gaps. By adjusting etching time and Ag film thickness, the CSP dips can be tuned to sweep the entire optical range of 360 to 1800 nm without changing sphere size, which makes them a promising candidate for forming integrated plasmonic sensing arrays. The high tunability of the CSP resonant frequencies together with strong electric field enhancement in the cavities make the ACAs promising candidates for surface plasmon sensors and SERS substrates, as, for example, they have been used in liquid refractive index (RI) sensing, demonstrating a sensitivity of 1505 nm/RIU and a figure of merit of 9. One of the CSP dips of ACAs with a certain geometry size is angle- (0-70 degrees) and polarization-independent and can be used as a narrow-band absorber. Furthermore, the nano annular cavity arrays can be used to construct solar cells, nanolasers and nanoparticle plasmonic tweezers.