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Polymer materials encapsulating drugs have broad prospects for drug delivery. We evaluated the effectiveness of polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG) encapsulation and release characteristics of PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235). We proposed a strategy for targeting radiosensitization of liver cancer cells. The biocompatibility, cell interaction, and internalization of Glypican-3 (GPC3) antibody-modified, BEZ235-loaded PLGA-PEG nanoparticles (NP-BEZ235-Ab) in hepatoma cells in vitro were studied. Also, the cell killing effect of NP-BEZ235-Ab combined with γ-ray cell was evaluated. We used confocal microscopy to monitor nanoparticle-cell interactions and cellular uptake, conducted focus-formation experiments to analyze the synergistic biological effects of NP-BEZ235-Ab and priming, and studied synergy in liver cancer cells using molecular biological methods such as western blotting. We found that PLGA-PEG has good loading efficiency for BEZ235 and high selectivity to GPC3-positive HepG2 liver cancer cells, thus documenting that NP-BEZ235-Ab acts as a small-molecule drug delivery nanocarrier. At the nominal concentration, the NP-BEZ235-Ab nanoformulation synergistically kills liver cancer cells with significantly higher efficiency than does the free drug. Thus, NP-BEZ235-Ab is a potential radiosensitizer. Graphical Abstract

Desensitization of hepatocellular carcinoma (HCC) to paclitaxel chemotherapy is a major deterrent to successful treatment of the cancer. Abnormal activation of the PI3K/Akt/mTOR, pathway is a common outcome of chemotherapy for HCC. Therefore, we investigated whether BEZ235, a dual PI3K and mTOR inhibitor, could increase the sensitivity of HCC to paclitaxel. In vitro results showed that paclitaxel, combined with BEZ235, inhibited HCC cell proliferation and migration, arrested the cell cycle in the G(2)/M phase, and promoted cell apoptosis by decreasing PI3K/Akt/mTOR activity. In vivo experiments confirmed that BEZ235 enhances the anti-tumor effect of paclitaxel by reducing PI3K/Akt/mTOR activity. Immunohistochemical staining showed that paclitaxel combined with BEZ235 reduced the numbers of Ki-67- and GPC3-positive HepG2 cells in tumor tissues. We conclude that BEZ235 enhanced the sensitivity of HCC to paclitaxel, and inhibition of PI3K/Akt/mTOR signaling might be a therapeutic strategy against paclitaxel-resistant HCC.

Roseomonas is a recently proposed genus of pink-pigmented, non-fermentative, short gram-negative rod-bacteria which have been recognized as a cause of human infections. We report a case of bacteremia associated with Roseomonas mucosa isolated from a patient with a history of nodular goiter and multiple episodes of blood transfusion. Key words: Roseomonas mucosa, myelodysplastic syndrome, case report.

Autophagy plays critical roles in plant responses to stress. In contrast to the wealth of information concerning the core process of plant autophagosome assembly, our understanding of the regulation of autophagy is limited. In this study, we demonstrated that transcription factor HsfA1a played a critical role in tomato tolerance to drought stress, in part through its positive role in induction of autophagy under drought stress. HsfA1a expression was induced by drought stress. Virus-induced HsfA1a gene silencing reduced while its overexpression increased plant drought tolerance based on both symptoms and membrane integrity. HsfA1a-silenced plants were more sensitive to endogenous ABA-mediated stomatal closure, while its overexpression lines were resistant under drought stress, indicating that phytohormone ABA did not play a major role in HsfA1a-induced drought tolerance. On the other hand, HsfA1a-silenced plants increased while its overexpression decreased the levels of insoluble proteins which were highly ubiquitinated under drought stress. Furthermore, drought stress induced numerous ATGs expression and autophagosome formation in wild-type plants. The expression of ATG10 and ATG18f, and the formation of autophagosomes were compromised in HsfA1a-silenced plants but were enhanced in HsfA1a-overexpressing plants. Both electrophoretic mobility shift assay and chromatin immunoprecipitation coupled with qPCR analysis revealed that HsfA1a bound to ATG10 and ATG18f gene promoters. Silencing of ATG10 and ATG18f reduced HsfA1a-induced drought tolerance and autophagosome formation in plants overexpressing HsfA1a. These results demonstrate that HsfA1a induces drought tolerance by activating ATG genes and inducing autophagy, which may promote plant survival by degrading ubiquitinated protein aggregates under drought stress.

Periodontitis is one of the most common chronic inflammatory disease triggered by microbial dysbiosis and is considered to be the major cause of losing tooth in the adult. With the development of oral implantology, dental implant has become widely accepted alternative method for replacing poor prognosis teeth in patients with periodontitis. However, over the years, researchers have been concerned about the prognosis and clinical survival of patients with periodontitis after implant treatment. Studies have shown that individuals with previous tooth loss caused by periodontitis have an increased risk of loss implants, peri-implant marginal bone loss, and peri-implantitis. The aim of the present review was to evaluate the risk indicators for implant therapy on periodontitis.

Highlight High CO2 concentrations can counteract the negative impact of salt stress in an apoplastic H2O2-dependent manner by regulating stomatal movement and Na+ delivery from the xylem to leaf cells., Plants acclimate rapidly to stressful environmental conditions. Increasing atmospheric CO2 levels are predicted to influence tolerance to stresses such as soil salinity but the mechanisms are poorly understood. To resolve this issue, tomato (Solanum lycopersicum) plants were grown under ambient (380 μmol mol–1) or high (760 μmol mol–1) CO2 in the absence or presence of sodium chloride (100mM). The higher atmospheric CO2 level induced the expression of RESPIRATORY BURST OXIDASE 1 (SlRBOH1) and enhanced H2O2 accumulation in the vascular cells of roots, stems, leaf petioles, and the leaf apoplast. Plants grown with higher CO2 levels showed improved salt tolerance, together with decreased leaf transpiration rates and lower sodium concentrations in the xylem sap, vascular tissues, and leaves. Silencing SlRBOH1 abolished high CO2 -induced salt tolerance and increased leaf transpiration rates, as well as enhancing Na+ accumulation in the plants. The higher atmospheric CO2 level increased the abundance of a subset of transcripts involved in Na+ homeostasis in the controls but not in the SlRBOH1-silenced plants. It is concluded that high atmospheric CO2 concentrations increase salt stress tolerance in an apoplastic H2O2 dependent manner, by suppressing transpiration and hence Na+ delivery from the roots to the shoots, leading to decreased leaf Na+ accumulation.