Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice.

Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow fever virus (YFV), which remains a potential threat to public health. The live-attenuated YF vaccine (17D strain) is a safe and highly effective measure against YF. However, increasing adverse events have been associated with YF vaccinations in recent years; thus, safer, alternative vaccines are needed.

Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain.

The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14.

A novel dengue virus serotype 1 vaccine candidate based on Japanese encephalitis virus vaccine strain SA14-14-2 as the backbone.

To develop a potential dengue vaccine candidate, a full-length cDNA clone of a novel chimeric virus was constructed using recombinant DNA technology, with Japanese encephalitis virus (JEV) vaccine strain SA14-14-2 as the backbone, with its premembrane (prM) and envelope (E) genes substituted by their counterparts from dengue virus type 1 (DENV1). The chimeric virus (JEV/DENV1) was successfully recovered from primary hamster kidney (PHK) cells by transfection with the in vitro transcription products of JEV/DENV1 cDNA and was identified by complete genome sequencing and immunofluorescent staining. No neuroinvasiveness of this chimeric virus was observed in mice inoculated by the subcutaneous route (s.

Construction and preliminary investigation of a novel dengue serotype 4 chimeric virus using Japanese encephalitis vaccine strain SA14-14-2 as the backbone.

For the purpose of developing a novel dengue vaccine candidate, recombinant plasmids were constructed which contained the full length cDNA clone of Japanese encephalitis (JE) vaccine strain SA14-14-2 with its premembrane (PreM) and envelope (E) genes replaced by the counterparts of dengue virus type 4 (DENV4). By transfecting the in vitro transcription products of the recombinant plasmids into BHK-21 cells, a chimeric virus JEV/DENV4 was successfully recovered. The chimeric virus was identified by complete genome sequencing, Western blot and immunofluorescent staining.

Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo.

Background: Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated.

Methods: The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry.

Activation of p53 by sodium selenite switched human leukemia NB4 cells from autophagy to apoptosis.

It was revealed by our previous research that sodium selenite repressed autophagy accompanied by the induction of apoptosis in human leukemia NB4 cells. The inhibition of autophagy exerted a facilitative effect on apoptosis. In the present study, we further explored the mechanisms underlying the switch from autophagy to apoptosis and elucidated p53 played a key role.

Heat shock protein 90-mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells.

Autophagy can protect cells while also contributing to cell damage, but the precise interplay between apoptosis and autophagy and the contribution of autophagy to cell death are still not clear. Previous studies have shown that supranutritional doses of sodium selenite promote apoptosis in human leukemia NB4 cells. Here, we report that selenite treatment triggers opposite patterns of autophagy in the NB4, HL60, and Jurkat leukemia cell lines during apoptosis and provide evidence that the suppressive effect of selenite on autophagy in NB4 cells is due to the decreased expression of the chaperone protein Hsp90 (heat shock protein 90), suggesting a novel regulatory function of Hsp90 in apoptosis and autophagy.

Downregulation of protein kinase Cα was involved in selenite-induced apoptosis of NB4 cells.

We revealed in our previous research that sodium selenite induced obvious apoptosis of human leukemia NB4 cells, with reactive oxygen species (ROS), mitochondrial apoptosis pathway, and endoplasmic reticulum stress (ER stress) involved. In the present study, we revealed protein kinase Ca (PKCalpha) was dramatically downregulated in selenite-induced apoptosis, which was mediated by ROS. Besides, we confirmed PKCalpha played an antiapoptotic role through its effects on ERK1/2 and Akt, while its downregulation was attributed to caspase-3 and PP2Ac under the regulation of ROS.

ROS leads to MnSOD upregulation through ERK2 translocation and p53 activation in selenite-induced apoptosis of NB4 cells.

Following our previous finding that sodium selenite induces apoptosis in human leukemia NB4 cells, we now show that the expression of the critical antioxidant enzyme manganese superoxide dismutase (MnSOD) is remarkably elevated during this process. We further reveal that reactive oxygen species (ROS), especially superoxide radicals, play a crucial role in selenite-induced MnSOD upregulation, with extracellular regulated kinase (ERK) and p53 closely implicated. Specifically, ERK2 translocates into the nucleus driven by ROS, where it directly phosphorylates p53, leading to dissociation of p53 from its inhibitory protein mouse double minute 2 (MDM2).

[Mechanism for downregulation of cytochrome c oxidase subunit IV in NB4 cells induced by sodium selenite].

Objective: To explore the mechanism and significance of cytochrome c oxidase subunit IV (COX IV) downregulation during apoptosis of NB4 cells induced by sodium selenite.

Methods: NB4 cells were treated with 20 micromol/L sodium selenite at different time points. COX IV protein and mRNA were detected by Western blot and RT-PCR, respectively.

The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice.

The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet.

The subcellular distribution of MnSOD alters during sodium selenite-induced apoptosis.

It was reported that high doses of sodium selenite can induce apoptosis of cancer cells, but the molecular mechanisms are poorly understood. Manganese superoxide dismutase (MnSOD) converts superoxide radical to hydrogen peroxide within the mitochondrial matrix and is one of the most important antioxidant enzymes. In this study, we showed that 20 microM sodium selenite could alter subcellular distribution of MnSOD, namely a decrease in mitochondria and an increase in cytosol.

Exposure of human leukemia NB4 cells to increasing concentrations of selenite switches the signaling from pro-survival to pro-apoptosis.

Selenium at low concentrations has a chemopreventive role against cancer, while at high concentrations, selenite exerts a direct antitumor effect. However, the mechanisms behind these effects remain elusive. In this study, we found that different concentrations of selenite triggered different signal pathways in human leukemia NB4 cells.

Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells.

Introduction: In this study, we delineated the apoptotic signaling pathways activated by sodium selenite in NB4 cells.

Materials And Methods: NB4 cells were treated with 20 microM sodium selenite for different times. The activation of caspases and ER stress markers, ROS levels, mitochondrial membrane potential and cell apoptosis induced by sodium selenite were analyzed by immunoblotting analysis, DCF fluorescence and flow cytometric respectively.

P53 transcription-independent activity mediates selenite-induced acute promyelocytic leukemia NB4 cell apoptosis.

Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. We have previously shown that sodium selenite can induce apoptosis by activating the mitochondrial apoptosis pathway in NB4 cells. However, the detailed mechanism remains unclear.