In support of its effect on the NF-kappa B signaling pathway, CucE decreased the phosphorylation levels of inhibitor of kappa B (I kappa B) and NF-kappa B/p65 in PDB + Ion-stimulated cells. Further supporting this, the nuclear translocation of NF-kappa B/p65 was significantly suppressed in

response to PDB plus Ion stimulation in the presence of CucE. The phosphorylation of p38MAPK, c-Jun N-terminal kinase (JNK), and Erk1/2, however, was not decreased or slightly increased at some time points by CucE treatment. Collectively, MEK inhibitor these data suggest that CucE may exhibit immunosuppressive effect by attenuating critical cytokine expression through down-regulating the NF-kappa B signaling pathway.”
“HBx is an oncogenic tumor-associated antigen and is dominantly expressed in hepatitis and hepatoma tissues, the induction of active cellular responses against HBx should be a promising approach for the treatment of hepatitis B virus-related hepatocellular carcinoma. The present study was designed to test whether a replication-defective adenovirus vaccine expressing HBx antigen could be effectively used in the immunotherapy of hepatocellular carcinoma. To validate the possibility, we developed a novel HBx-positive hepatocellular P005091 in vivo carcinoma in mice by inoculated the pcDNA-HBx transfected Hepa1-6 cells subcutaneously

into the right flank of mice. We found that immunotherapy with Ad-HBx was effective at both protective and therapeutic antitumor immunity in the

hepatoma models in immune-competent mice. Histological examination revealed that Ad-HBx treatment led to significantly increased induction of apoptosis, tumor necrosis, FK506 concentration and elevated CD8(+) lymphocyte infiltration. In addition, the induction efficacy of the CTL response is dramatically enhanced by immunotherapy. Cytokine analysis comfirmed that the antitumor efficacy of Ad-HBx may mostly result from cellular immunity. Our findings may prove useful in development of adenovirus vaccine based on HBx antigen to the treatment of HBV-associated hepatocellular carcinoma.”
“Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells.