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Objective Due to high cytotoxicity effect, ribonucleases (RNases) are known as pharmacological agents with therapeutic potential. The high potential of these enzymes in the destruction of RNA strand and their other substrates and subsequently, cell destruction or cessation of cell division causes a very high cytotoxic effect of this enzyme in various cancer cells. Hence, this review investigates the therapeutic applications of ribonucleases, cell pathways and their mode of action as cytotoxic agents in order to pay attention to them in researches related to the health and therapy fields. Materials and methods In this study the keywords such as cancer, ribonuclease, ribonuclease inhibitor and RNA were used to search in databases including Scopus, SID, IranDoc, PubMed, Google Scholar, Web of Science and IranMedex. In order to select the documents used, all articles published in non-English and Persian languages, duplicate articles, articles that could not be accessed to the full text, as well as articles that were presented as abstracts were removed. Finally, the selected cases were thoroughly studied and summarized in order to prepare the current review. Results The study and review of research conducted showed that ribonucleases have the ability to kill tumor cells and that these enzymes have antiviral properties. Bovine pancreatic ribonuclease (RNase A), bovine seminal ribonuclease (BS-RNase), Onconase, and angiogenin are known as RNases with high antitumor activity which exert cytotoxic activity on cancer cells selectively by involving different cellular pathways and/ or enhance the cytotoxicity by mutation. Also, the study of articles related to the function of ribonucleases showed that the investigation of genetic pathways of synthesis and mechanisms of cytotoxicity in these enzymes will provide the development of new pharmaceutical products in the future. Utilization of engineering processes and chemical changes in ligand / receptor structure may increase the toxicity of ribonuclease molecules in order to select cytotoxic pathways on malignant cells. Therefore, it is necessary to discover the therapeutic potential and to study in detail the therapeutic values of ribonucleases. Conclusions Ribonucleases are potentially bioavailable drug candidates, and in regard to their toxicity, which is based on the selective hydrolysis of intracellular RNA molecules and specific cell membrane recognition processes, these enzymes can be used as anti-tumor drugs or therapeutic agents.

Objective Immunotoxins are one of the most promising ways in therapeutic fields, specially cancer therapy which have a unique toxin-antibody structure, and kill the cancer cell by passing through the cell membrane and entering the target cell. The aim of this study was to engineer and design bovine pancreatic enzyme (RNase A) for to escape from ribonuclease inhibitor (RI) as a toxin segment in designing of immunotoxins used in therapeutic fields. Materials and Methods After bioinformatics investigation using PyMol software, engineering and substitution of target amino acid in wild gene coding RNase A sequence (K91A) were performed. The wild type and recombinant proteins in E.coli (BL21(D3) strain) were expressed and refolded, and then approved using SDS-PAGE. The purification of produced proteins was conducted using an immobilized-metal affinity chromatography for His-tagged proteins. Results The results showed that the protein concentrations were 3 and 2.2 g/L for wild RNase A and recombinant enzyme. The hydrolysis activity measurement of the produced enzymes, in presence of different concentrations of RI, indicated that recombinant variant had lower sensitivity and higher catalytic activity in comparison with the wild enzyme. The results obtained from enzyme activity of recombinant enzyme compared to the wild enzyme, in presence or absence of RI, demonstrated that the interaction effect between RNase A and RI can be disrupted by manipulation of amino acids involved in this interaction. Conclusion In respect to the current results, it was concluded that RNase A enzyme can be used as a promising drug in engineering and production of immunotoxins.

Objective Salmonella is a Gram-negative, anaerobic, flagellated bacterium of Salmonella type in Enterobacteriaceae family, which is known as a zoonosis infectious agent. In recent years, different types of antibiotics have been used to overcome the Salmonella infection; however, the increasing number of antibiotic-resistant bacteria, the provision of alternative methods seems be necessary. Specific immunoglobulin Y (IgY) originated from egg yolk causes passive immunity in the fetus, and extracting these antibodies from egg yolk is cheaper and more feasible than other antibodies. Numerous studies have shown that the egg yolk IgY has immunogenic function against a wide range of bacterial and viral infections in mammals. The purpose of this study was to produce specific immunoglobulin Y against Salmonella typhimurium and Salmonella enteritidis bacteria in laying hens. Materials and Methods In the current study, six pullets were inoculated and boosted with one milliliter of killed Salmonella typhimurium and Salmonella enteritidis. Injections were done fortnightly until one week before egg production. After breast muscle injection of chickens, the eggs were collected, and the IgY was extracted from yolk by the Polson method with polyethylene glycol 6000. The produced IgY was approved by SDS-PAGE method. The specific indirect ELISA done by specificity test for purified IgY also approved the specific IgY against both Salmonella typhimurium and Salmonella enteritidis. Results The results of SDS - PAGE demonstrated the presence of two protein bands of 27 and 67 kDa representing light and heavy chains of IgY, respectively. The specific indirect ELISA method proved that the specific IgY against Salmonella typhimurium and Salmonella enteritidis was produced in the egg yolk. Conclusions It might be possible to administer the egg yolk containing specific IgY against both Salmonella typhimurium and Salmonella enteritidis, to induce passive immunity for preventing some pathogenic diseases in calves such as diarrhea.