Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and connected using linkers for designing the vaccine construct. The secondary and tertiary models of the designed vaccine were generated and satisfactorily validated. A Ramachandran plot of the final 3D model showed more than 90% of the residues in allowed regions and only 0.4% in disallowed regions. The binding affinity of a vaccine construct with TLR 2, 3 and 4 receptors was assessed through molecular docking and simulation. The average numbers of hydrogen bonds for vaccine-TLR 2, 3 and 4 complexes in the simulation were 15.36, 16.45, and 11.98, respectively, and remained consistent over a 100 ns simulation period, which is critical for their function. The results of this study provide a strong basis for further evaluation through in vitro/in vivo experimental validation of the safety and efficacy of the designed vaccine construct.

Effect of bifenthrin on oxidative stress parameters in the liver, kidneys, and lungs of rats.

Oxidative stress inducing potential of bifenthrin was evaluated in the liver, kidney, and lung of rats following its repeated oral administration for 20 and 30 days. Bifenthrin-treated rats showed a significant lipid peroxidation in all three tissues. By 20th day of treatment, there was a significant decrease in superoxide dismutase activity of the liver, catalase and glutathione peroxidase activity of the liver and lung, and glutathione S-transferase activity of the kidney and lung. By 30th day of exposure, the activities of these enzymes were significantly decreased in all three tissues. The highest oxidative stress, indicated by lipid peroxidation and alteration in antioxidant enzymes, is produced in the liver followed by the kidney and lung. In conclusion, bifenthrin has a potential to induce severe oxidative stress in the liver, kidney, and lung. The extent of oxidative stress is increased with the duration of exposure.

Effect of repeated oral administration of bifenthrin on lipid peroxidation and anti-oxidant parameters in Wistar rats.

The oxidative stress-inducing potential of the pyrethroid insecticide, bifenthrin, was evaluated in rats at 5.8 mg/kg body weight once daily for 20 or 30 days. Bifenthrin treated animals showed significantly increased lipid peroxidation, evidenced by increased blood malondialdehyde levels. Blood glutathione levels and activities of catalase and glutathione peroxidase decreased significantly in the bifenthrin treated animals after both 20 and 30 days of treatment, whereas, the activities of superoxide dismutase and glutathione S-transferase decreased significantly only on the 30th day. In conclusion, bifenthrin has a potential to induce severe oxidative stress in rats exposed to sublethal concentrations.