Designing a potent L1 protein-based HPV peptide vaccine : a bioinformatics approach

Background: Oncogenic human papilloma viruses (HPV) are the cause of various types of cancer, specifically cervical cancer. L1 protein is the main protein of HPV capsid which targeted in many vaccine-producing attempts. However, they have not enough coverage on the various high risk HPV types. Therefore, having a low cost potent HPV vaccine to protect against all members of the ɑ-papillomaviridea family will be promising. In this study, L1 protein-based peptide vaccine was designed using immunoinformatics methods which provides physicochemical properties such as stability in room temperature, potential of antigenicity, non-allergic properties and no requirement with eukaryotic host system. Results: The designed vaccine has two HPV conserved epitopes with lengths 18 and 27 amino acids in all members of α-papillomaviridea. These peptides promote humoral and cellular immunity and INF-γ responses. In order to ensure strong induction of immune responses, Flagellin, a Toll like receptor 5(TLR-5) agonist, and a short synthetic toll like receptor 4 (TLR-4) agonist were also joined to the epitopes. Structure of the designed- vaccine was validated using Rampage and ERRAT and a high quality 3D structure of the vaccine protein was provided. Docking studies demonstrated an appropriate and stable interaction between the vaccine and TLR-5. Conclusions: The vaccine is expected to have a high quality structure and suitable properties including high stability, solubility and a high potential to be expressed in 'E.coli'. High potentiality of the vaccine in inducing humoral and cellular immune responses, may be considered as an anti-tumor vaccine

Immune Dysregulation in Children with Allergic asthma, a close Relationship between IL-17 but not IL-4 or IFN-g, and Disease Severity

Background : Allergic asthma is a chronic airway inflammatory disease often determined with degrees of inflammation, hypersensitivity, bronchial constriction, and airway changes. Th1, Th2, and Th17 cells are the main cells involved in asthma pathophysiology. To evaluate Th1, Th2, and Th17 functions by assessing INF-g, IL-4, and IL-17 gene and protein levels in asthma patients and healthy controls. Materials and methods: In total, 44 individuals of Iranian ethnicity including 24 patients with allergic asthma and 20 healthy controls were enrolled. Peripheral blood mononuclear cells of all participants were isolated and cDNA was synthesized following RNA extraction. Gene expression and protein levels of INF-g, IL-4, and IL-17 were evaluated by real-time polymerase chain reaction and sandwich ELISA, respectively. Results: The results of this study showed that the gene expression of IL-4 and IL-17 in patients was increased significantly compared to the control group (p = 0.046 and 0.03, respectively) whereas that of IFN-g was significantly decreased in the group of patients (p = 0.021). Compared to the healthy controls, serum levels of IL-17 and IL-4 were significantly increased in asthma patients (p = 0.015 and 0.03, respectively). Conclusion: Higher IL-17 and IL-4 mRNA expression and serum levels in asthma patients than healthy controls highlight the role of Th2 and Th17 cells in asthma pathogenesis and their potential as therapeutic targets

Combination effect of cold atmospheric plasma with green synthesized zero-valent iron nanoparticles in the treatment of melanoma cancer model.

Green synthesized zero-valent iron nanoparticles (nZVI) have high potential in cancer therapy. Cold atmospheric plasma (CAP) is also an emerging biomedical technique that has great potential to cure cancer. Therefore, the combined effect of CAP and nZVI might be promising in treatment of cancer. In this study, we evaluated the combined effect of CAP and nZVI on the metabolic activity of the surviving cells and induction of apoptosis in malignant melanoma in comparison with normal cells. Therefore, the effect of various time exposure of CAP radiation, different doses of nZVI, and the combined effect of CAP and nZVI were evaluated on the viability of malignant melanoma cells (B16-F10) and normal fibroblast cells (L929) at 24 h after treatment using MTT assay. Then, the effect of appropriate doses of each treatment on apoptosis was evaluated by fluorescence microscopy and flow cytometry with Annexin/PI staining. In addition, the expression of BAX, BCL2 and Caspase 3 (CASP3) was also assayed. The results showed although the combined effect of CAP and nZVI significantly showed cytotoxic effects and apoptotic activity on cancer cells, this treatment had no more effective compared to CAP or nZVI alone. In addition, evaluation of gene expression showed that combination therapy didn't improve expression of apoptotic genes in comparison with CAP or nZVI. In conclusion, combined treatment of CAP and nZVI does not seem to be able to improve the effect of monotherapy of CAP or nZVI. It may be due to the resistance of cancer cells to high ROS uptake or the accumulation of saturated ROS in cells, which prevents the intensification of apoptosis