Immunization of mice by the co-administration of codon-optimized HPV16 E7 and lL12 genes against HPV16-associated cervical cancer

Background: Various promising procedures have been used to improve the potency of DNA vaccines for the treatment of human papillomavirus type 16 (HPV16) infections. Interleukin-12 (IL12) is a powerful adjuvant that can contribute to T cell-mediated protection against many pathogens, specifically viruses. Considering the important role of T cell-mediated immunity in tumor clearance, the induction of these responses can help control the progression of tumors in animal models. We have demonstrated that the co-administration of codon-optimized E7 (uE7) gene of HPV16 with interleukin-12 is effective in the development of antitumor responses. Objectives: The present study examined the co-administration of codon-optimized HPV16 E7 gene with murine interleukin-12 gene (mIL-12) as a vaccine adjuvant in tumor mice model. Materials and methods: C57BL/6 mice were studied for tumor progression after injection of recombinant DNA vaccines. Lactate dehydrogenase (LDH) and IFN-γ were measured to evaluate the activity of cytotoxic T lymphocytes (CTLs). Measurements of tumor volume and MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used for assessment of therapeutic antitumor effects of the vaccines. Results: Results showed that DNA vaccines, specifically codon-optimized E7/murine interleukin-12 (mIL-12), elicited significant differences in levels of IFN-γ and cytotoxic T lymphocyte (CTLs) responses compared to control groups. Furthermore, higher antitumor response and lower tumor size in the vaccine group was significantly evident compared to control group. Conclusion: The co-administration of codon-optimized HPV16 E7 gene with IL12 significantly enhances the DNA vaccine potency against HPV16-associated cervical cancer. © 2019 Elsevier Lt

Hepatitis C virus alternative reading frame protein (ARFP): Production, features, and pathogenesis

Earlier observation suggests that hepatitis C virus (HCV) is a single-stranded RNA virus which encodes at least 10 viral proteins. F protein is a novel protein which has been discovered recently. These studies suggest three mechanisms for the production of this protein concerning ribosomal frameshift at codon 10, initial translation at codons 26 and 85 or 87. In this study, the association between protein F and chronicity of hepatocellular carcinoma (HCC) has been reviewed. Evidence suggests that humoral immune system can recognize this protein and produce antibodies against it. By detecting antibodies in infected people, investigators found that F protein might have a role in HCV infection causing chronic cirrhosis and HCC as higher prevalence was found in patients with mentioned complications. The increment of CD4+, CD25+, and FoxP3+ T cells, along with CD8+ T cells with low expression of granzyme B, also leads to weaker responses of the immune system which helps the infection to become chronic. Moreover, it contributes to the survival of the virus in the body through affecting the production of interferon. F protein also might play roles in the disease development, resulting in HCC. The existence of F protein affects cellular pathways through upregulating p53, c-myc, cyclin D1, and phosphorylating Rb. This review will summarize these effects on immune system and related mechanisms in cellular pathways. © 2020 Wiley Periodicals LL

The Influence of Probiotics Consumption on Management of Prediabetic State: A Systematic Review of Clinical Trials

Prediabetes consists of the intermediary stage between normal glucose regulation and overt diabetes mellitus and develops when blood glucose levels are higher than normal but not high enough to confirm a type 2 diabetes mellitus diagnosis (T2DM). Recent evidence suggests that probiotics could be promising approaches to improve this state. In this study, we performed a systematic review to compile the results of clinical trials investigating the effects of pro-/pre-/synbiotics on prediabetes subjects from 2010 to 2020. The article search was carried out in Medline, Embase, Scopus, Web of Science, The Cochrane Library, Clinical trials.gov, ProQuest, Open Grey, and Google Scholar. Search filters were developed using 2 parameters: "prestate diabetes" and "probiotics." Of the 418 studies that were screened, 15 original articles reached the inclusion criteria. Pooling data from these trials showed positive and significant effects of probiotics in the reduction of hyperglycemia, insulin concentration levels, lipid profile, and BMI (Body mass index). Administration of probiotics may provide beneficial and healthful effects in the clinical management of patients with prediabetes and metabolic syndrome. Different probiotics compositions have shown beneficial and noticeable effects on glucose homeostasis, lipid profiles, BMI, and inflammatory markers in subjects with prediabetes, metabolic syndrome, and healthy individuals and could be advantageous in recomposing the gut microbiota back into the normal state during the prediabetic state

Evaluation and Phylogenetic Analysis of Regular Rabies Virus Vaccine Strains

Background: This study aimed to evaluate Rabies virus vaccine strains. The obtained results may be helpful for vaccine producers and researchers to compare the strains with wild type and other vaccine strains and select the correct strain to challenge their products.Methods: Fourteen rabies virus vaccine strains were compared with each other. The full genomes of the selected strains were taken from the GenBank and the N, P and G genes were labeled. The major and minor antigenic sites of these sequences were identified and contrasted with each other. The identity matrix was designed for rabies virus full genome, N and G genes. In addition, the phylogenetic tree was drawn based on rabies virus N gene for deep analysis.Results: Although there were no significant differences between antigenic sites in N, P, and G genes, there were noticeable differences for full genome identity matrix and this significant difference can also be observed in N and G identity matrix. In the phylogenetic tree, the Iranian sequences were distant from currently applied vaccine strains.Conclusion: It is necessary to pay attention to the results shown in phylogenetic tree because they warn us about distance between the Iranian sequences and current strains used in applied vaccines. In addition, the obtained results help vaccine producers to choose a correct strain to challenge their product and evaluate their vaccine potency

Evaluation and phylogenetic analysis of regular rabies virus vaccine strains

Background: This study aimed to evaluate Rabies virus vaccine strains. The obtained results may be helpful for vaccine producers and researchers to compare the strains with wild type and other vaccine strains and select the correct strain to challenge their products. Methods: Fourteen rabies virus vaccine strains were compared with each other. The full genomes of the selected strains were taken from the GenBank and the N, P and G genes were labeled. The major and minor antigenic sites of these sequences were identified and contrasted with each other. The identity matrix was designed for rabies virus full genome, N and G genes. In addition, the phylogenetic tree was drawn based on rabies virus N gene for deep analysis. Results: Although there were no significant differences between antigenic sites in N, P, and G genes, there were noticeable differences for full genome identity matrix and this significant difference can also be observed in N and G identity matrix. In the phylogenetic tree, the Iranian sequences were distant from currently applied vaccine strains. Conclusion: It is necessary to pay attention to the results shown in phylogenetic tree because they warn us about distance between the Iranian sequences and current strains used in applied vaccines. In addition, the obtained results help vaccine producers to choose a correct strain to challenge their product and evaluate their vaccine potency. © 2018 The Author(s)

Carthamus, Salvia and Stachys species protect neuronal cells against oxidative stress-induced apoptosis.

Abstract Context: Finding effective therapies for neurodegenerative diseases is of utmost importance for the aging population. Plants growing in Iran are rich sources of antioxidants and active phytochemicals.The protective capacity of plants, with a special focus on those with reported antioxidant or neuroprotective potential or nervous system-related applications in folk medicine, was tested against oxidative stress-induced apoptosis.Aerial parts of 20 plants including Carthamus, Salvia, and Stachys species were extracted with 80\% methanol and dichloromethane and preincubated with neuronal PC12 cells for 3 h. Oxidative stress and apoptosis were induced by hydrogen peroxide (75 µM, 1 h exposure). Cell viability and intracellular reactive oxygen species (ROS) were measured by MTT and 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assays, respectively, while apoptosis was determined by annexin V-FITC/propidium iodide staining by a flow cytometer.Eighty percent methanol extracts of Carthamus oxyacantha Bieb. (Asteraceae), Salvia santolinifolia Boiss. (Lamiaceae), and Salvia sclarea L. (Lamiaceae) at the concentration of 100 μg/ml showed significant neuroprotection in the MTT assay by 38.7, 34.7, and 39.5\%, respectively, and inhibited intracellular ROS by 48.6, 61.9, and 61.4\%, respectively. The first two extracts also significantly inhibited apoptosis. Dichloromethane extracts of C. oxyacantha and Stachys pilifera Benth. (Lamiaceae) at the concentration of 25 μg/ml showed neuroprotection by 27.5 and 26.5\%, respectively, and inhibited ROS by 44.5 and 39.4\%, respectively.The above-mentioned plants seem to have important biological activities and their further study may lead to the discovery of new natural therapeutics useful against disorders such as Alzheimer and Parkinson diseases