RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway

Initial functional studies have demonstrated that RNA‐binding motif protein 10 (RBM10) can promote apoptosis and suppress cell proliferation; however, the results of several studies suggest a tumour‐promoting role for RBM10. Herein, we assessed the involvement of RBM10 in lung adenocarcinoma cell proliferation and explored the potential molecular mechanism. We found that, both in vitro and in vivo, RBM10 overexpression suppresses lung adenocarcinoma cell proliferation, while its knockdown enhances cell proliferation. Using complementary DNA microarray analysis, we previously found that RBM10 overexpression induces significant down‐regulation of RAP1A expression. In this study, we have confirmed that RBM10 decreases the activation of RAP1 and found that EPAC stimulation and inhibition can abolish the effects of RBM10 knockdown and overexpression, respectively, and regulate cell growth. This effect of RBM10 on proliferation was independent of the MAPK/ERK and P38/MAPK signalling pathways. We found that RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway.     

Molecular characterization of heat shock protein 70 genes in the liver of three warm freshwater fishes with differential tolerance to microcystin-LR

Heat shock protein 70 (HSP70) protect cell from oxidative stress by preventing the irreversible loss of vital proteins and facilitating their subsequent regeneration. Silver carp (Hypophthalmichthys molitrix), grass carp (Ctenopharyngodon idellus), and Nile tilapia (Oreochromis nilotica) are three warm freshwater fishes with differential tolerance to microcystin-LR (MC-LR). Full-length cDNAs encoding the HSP70 were cloned from the livers of the three fishes. The HSP70 cDNAs of silver carp, grass carp, and Nile tilapia were 2356, 2348, and 2242 bp in length and contained an open-reading frame of 1950 bp (encoding a polypeptide of 649 amino acids), 1950 bp (649 amino acids), and 1917 bp (638 amino acids), respectively. Like mammalian HSP70, the HSP70 of the three fish was also composed of an ATPase domain from residues 1 to 383 (44 kDa), substrate peptide binding domain from residues 384 to 544 (18 kDa), and a C-terminus domain from residues 545 to 649 (10 kDa). The relatively high conservation of HSP70 sequences among different vertebrates is consistent with their important role in fundamental cellular processes. Using beta-actin as an external control, RT-PCR within the exponential phase was conducted to determine the constitutive and inducible expression level of HSP70 gene among the three fishes (6-12 g) intraperitoneally injected with MC-LR (50 μg kg(-1) body weight). Both constitutive and inducible liver mRNA levels of the fish HSP70 genes showed positive relationships with their tolerance to MC-LR: highest in Nile tilapia, followed by silver carp, and lowest in grass carp. The differential expression pattern of liver HSP70 genes in the three fish indicated a potential role of HSP70 in the detoxification process of MC-LR.     

Dendritic cells transduced with lentiviral vector targeting RelB gene using RNA interference induce hyporesponsiveness in memory CD4(+) T cells and naïve CD4(+) T cells

The ability of DCs to induce immune tolerance depends on its maturation status. RelB plays a pivotal role in DCs differentiation. A therapeutic protocol of DCs-based not only induces hyporesponsiveness in T(N)s, but also in alloreactive T(M)s is required. Thus, it is urgent to assess modulatory effects of RelB-silenced DCs on T(M)s and T(N)s. In this study, we constructed lentiviral vector which could efficiently silenced the RelB in DCs (DCs-miR RelB) to keep them immature. These DCs induced antigen-specific hyporesponsiveness in CD4(+) T(N)s. In contrast, upon re-stimulation with mature DCs, CD4(+) T(M)s primed by DCs-miR RelB maintained hyporesponsiveness in terms of proliferation and cytokine production. And these may be associated with micro155 and micro181a expression levels in T(M)s and T(N)s. These results may help developing the DCs-based therapeutical protocols by inducing hyporesponsiveness in CD4(+) T(N)s and T(M)s.     

Screening and Identification of Marburg Virus Entry Inhibitors Using Approved Drugs

正Dear Editor,Marburg virus(MARV) belongs to the Filoviridae family,along with the related Ebola virus(EBOV). Although MARV is less renowned than EBOV, it causes an equally devastating disease, with clinical symptoms similar to EBOV infection and a remarkably high mortality rate. To     

Partial characterization of a hydrophobin protein Po.HYD1 purified from the oyster mushroom <Emphasis Type="Italic">Pleurotus ostreatus</Emphasis>

Hydrophobins fulfill various physiological functions in fungal development and growth, based on their mechanism of self-assembly at hydrophilic–hydrophobic interfaces into nano-scale, amphipathic membranes. One hydrophobin with an approximate molecular weight of 15 kDa, designated Po.HYD1, was purified from aerial hyphae of Pleurotus ostreatus strain Pm039. Ultrastructures of self-assembled films formed by Po.HYD1 on hydrophobic and hydrophilic substrates were revealed by atomic force microscopy (AFM). A monomolecular adsorption layer, thickness ranging from 3.2 to 3.8 nm, was observed on the surface of highly oriented pyrolytic graphite (HOPG), while a typical rodlet layer with uniform thickness of 4.2 ± 0.1 nm formed on the mica surface. Comparison of CD spectra showed significant secondary structural changes between monomeric and self-assembled states. The spectrum of monomeric Po.HYD1 had a maximum ellipticity at 190 nm and a minimum at 209 nm, and that of assemblage showed the maximum at 195 nm and the minimum shifted to 215–218 nm. Po.HYD1 showed high surface activity, based on the dramatic drop of surface tension through self-assembly at the water–air interface. Moreover, Po.HYD1 is capable of stabilizing the emulsion consisting of water and hexane.