Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway.

Prodigiosin (PG), a member of a family of natural red pigments produced by a variety of bacteria, was first discovered in Serratia marcescens. PG has been reported to have an apoptosis-inducing effect in many cancers, such as lymphoma, colon cancer and nasopharyngeal carcinoma. For this study, we used three glioblastoma (GBM) cell lines (LN229, U251 and A172) to explore the effect of prodigiosin on GBM cells. A CCK8 assay was used to evaluate cell viability. We determinedthe cell cycle distribution by flow cytometry and measured proliferation by an EdU incorporation assay. The expression of different molecules was investigated by western blotting and RT-PCR. We further confirmed our results by plasmid transfection and lentiviral transduction. The LN229 xenograft model was used to study the effect of prodigiosin in vivo. We confirmed that prodigiosin played an anticancer role in several GBM cell lines through the KIAA1524/PP2A/Akt signalling pathway. Prodigiosin inhibited the protein expression of KIAA1524 by suppressing its transcription, which led to activation of PP2A. Afterward, PP2A inhibited the phosphorylation of Akt, thereby inducing increased expression of p53/p21. Furthermore, it was verified that prodigiosin inhibited the KIAA1524/PP2A/Akt axis in vivo in the LN229 xenograft model. These data improve the understanding of the anticancer effects of prodigiosin and further highlight the potential of prodigiosin for the development of anti-glioma drugs.

Magnetically Recyclable Graphene Oxide Demulsifier Adapting Wide pH Conditions on Detachment of Oil in the Crude Oil-in-Water Emulsion.

In the present work, an amphiphilic and magnetically recyclable graphene oxide (MR-GO) demulsifier was devised and synthesized by graft of magnetic nanoparticles (Fe3O4@SiO2-APTES) and ethylenediamine on the GO surface. The wettability and surface charges of MR-GO under various pH conditions can be regulated via adjusting the contents and species of surface functional groups (such as amino, carboxyl, and hydroxyl). In the demulsificaition test, MR-GO displayed favorable demulsification performance for crude oil-in-water (O/W) emulsion under pH of 2.0-10.0, thusly greatly improving the application scope of common demulsifier. The optimal dosage of MR-GO was 200 mg/L and the demulsification efficiency attained a maximum value of 99.7% for crude O/W emulsion with pH of 6.0. What's more, owing to its magnetic response performance, the MR-GO can be reused and the demulsification efficiency remained above 91.0% after six cycles. Based on the strong interfacial activity, MR-GO can arrive to the crude oil-water interface. With the synergy effects of interfacial adsorption (π-π/n-π) interactions and electrostatic attraction of demulsifier and interfacial films, and the aid of external mechanical forces, the interfacial films stabilized the emulsion were disrupted. Therefore, the oil droplets coated on the water droplets were gathered rapidly to form oily flocs and then migrated to the water surface to accomplish the demulsification of crude O/W emulsion.

HBV infection suppresses the expression of inflammatory macrophage miR­210.

It has been previously reported that hepatitis B e­antigen (HBeAg) induces microRNA (miR)­155 expression and promotes liver injury by increasing inflammatory cytokine production in macrophages. Moreover, it was previously demonstrated that miR­210 alleviates lipopolysaccharide­stimulated proinflammatory cytokine production in macrophages. In addition, accumulating evidence suggests that miR­210 is able to suppress hepatitis B virus (HBV) replication in HepG2.2.15 cells. However, it remains unclear whether miR­210, similar to miR­155, affects the progress of hepatitis B by regulating macrophage function. Reverse transcription­quantitative polymerase chain reaction analysis was used to detect miR­210 levels in serum and cells. HBV­associated antigens stimulated different types of macrophages and facilitated the observation of the effects of these antigens on miR­210 expression in macrophages. Co­culture of peripheral blood monocytes from healthy controls and the serum of patients with chronic hepatitis B (CHB) was conducted to evaluate the effect of HBV­associated elements in the serum on the expression of the macrophage miR­210 in vivo. It was observed that miR­210 expression levels were decreased in the peripheral blood monocytes (PBMs) and serum of patients with CHB and negatively associated with serum alanine aminotransferase and aspartate aminotransferase, but not other clinical parameters including hepatitis B surface antigen (HBsAg), HBeAg, anti­HBe antibody (HBeAb) and hepatitis B core antibody (HBcAb) and HBV­DNA. Notably, it was demonstrated that miR­210 expression was not affected by treatment with HBV­associated antigens in different types of macrophages. Notably, the serum of patients with CHB was able to markedly downregulate the miR­210 expression of PBMs in healthy controls. These findings suggested that, unlike the induction of miR­155 by HBeAg, there may be certain other elements, apart from HBV­associated antigens, regulating miR­210 levels in the serum and PBMs of patients with CHB that affect macrophage activation.

A peptide-mediated targeting gene delivery system for malignant glioma cells.

Glioblastoma multiforme (GBM) is the most common and malignant glioma. Although there has been considerable progress in treatment strategies, the prognosis of many patients with GBM remains poor. In this work, polyethylenimine (PEI) and the VTWTPQAWFQWV (VTW) peptide were modified and synthesized into GBM-targeting nanoparticles. The transfection efficiency of U-87 (human glioblastoma) cells was evaluated using fluorescence microscopy and flow cytometry. Cell internalization was investigated to verify the nanoparticle delivery into the cytoplasm. Results showed that the methods of polymer conjugation and the amount of VTW peptide were important factors to polymer synthesis and transfection. The PEI-VTW20 nanoparticles increased the transfection efficiency significantly. This report describes the use of VTW peptide-based PEI nanoparticles for intracellular gene delivery in a GBM cell-specific manner.