Vol 3, No 3 (2021)

This study is focused on the two novel nucleases of the CRISPR/Cas9 family, which were found in bacterial genomes of DfCas9 (Defluviimonas sp) и DsCas9 (Demequina sediminicola). Discovery of these nucleases was part of the results of a joint study conducted by BIOCAD together with Skoltech Institute of Science and Technology and Saint-Petersburg Polytechnical University (SPPU) under a grant agreement with the Department of Science and Education of Russian Federation (Agreement number 14.606.21.0006 from September, 26th 2017). Under the agreement the nucleases DfCas9 and DsCas9 were characterized in vitro by Skoltech and SPPU.

Based on the aforementioned results, in this study we characterized the genome-modifying nuclease activity of these enzymes in a mammalian cell line HEK293. Specifically, we created genetic constructs designed to express the nucleases DsCas9 and DfCas9 together with the necessary guide RNA molecules (sequences of the guide RNAs were described previously) [1]. We demonstrated expression of the nucleases on a protein level, as well as activity of DfCas9 at the VEGF2 locus in HEK293 cells. The theoretical study was conducted by analyzing international and national literature. The experimental part was performed with a restriction-ligation cloning method, transient transfections, Western blot protein detection method, and a T7 nuclease-based method of detection of heteroduplex double-stranded DNA.

Malignant neoplasms (MNO) of esophagus is the localization with a high mortality rate. Years of searching for effective treatment in Russia have resulted in modest success. The median survival rate of patients is expressed in months, 70% of patients die in the first year of dispensary registration, the levels of one-year mortality rates for men and women practically do not differ.

The esophageal cancer (EC) morbidity and mortality rates have slightly decreased in 2000–2018 in Russia and has declined only among the male population of the Northwestern Federal District.

To study the trends in the morbidity and mortality rates in the population of Russia and the Northwestern Federal District of the Russian Federation. Qualitative analytical indicators, such as the accuracy index and the year-to-year mortality patterns in esophageal cancer patients, will be further considered.

The highest standardized EC morbidity rates of the population were found in Zimbabwe (Harare, Africans) – 15.5 0/0000, Japan (Miyage) – 14.3 0/0000 and the Arkhangelsk region of Russia – 12.8 0/0000. In 2000-2019 the level of standardized morbidity rates of the Russian population with EC has decreased from 3.44 to 3.19 0/0000 or 7.3% (both sexes), mortality rates – from 3.32 to 2.66 0/0000, or 19.9%. A decrease in the morbidity and mortality rates from EC occurred in the Northwestern Federal District of the Russian Federation, only among the male population.

Annual EC mortality rate mainly occurs according to the classical model. The highest level is determined in the first year of follow-up (72-74%); by the end of the decade, only 4.1% of patients remain from those initially recorded.

The accuracy index has decreased in Russia and in the Northwestern Federal District of the Russian Federation, respectively, to 0.84 and 0.86 (both sexes) but has remained above the critical mark of 0.7 for localizations with a high mortality rate.

In connection with the constantly increasing use of monoclonal antibodies labeled with ⁸⁹Zr, in clinical practice, it is urgent to study their pharmacokinetics with the determination, based on the data obtained, of absorbed doses in tumor foci, as well as intact organs and tissues, and effective doses of patients. To date, there are a limited number of studies that provide patient doses for diagnostic examinations using ⁸⁹Zr-labeled monoclonal antibodies. In this regard, the purpose of this work was to assess the biodistribution of various monoclonal antibodies (ramucirumab, trastuzumab, atezolizumab) labeled with ⁸⁹Zr, based on published data, with subsequent calculation of absorbed doses in radiosensitive organs and tissues and effective doses of patients.

Based on the analysis of experimental data on the biodistribution of monoclonal antibodies labeled with ⁸⁹Zr for the diagnosis of oncological diseases from the available literature sources and our own assessments, it has been concluded that the results of the determination of absorbed in organs and tissues and effective doses are inconsistent. The absorbed doses in organs, according to different literature sources, vary up to an order of magnitude within one organ and reach 440 mGy per examination, the effective dose varies from 3 to 112 mSv per examination. This may be due to differences in study design, radiometry and dose assessment methods. Comparison with doses obtained on the basis of a general model of biodistribution of monoclonal antibodies demonstrates the possibility of using this model for a rough estimate of internal doses of patients. However, for a more accurate assessment, it is necessary to standardize approaches to the determination of internal radiation doses using the most effective methodological solutions and software products.

Issues related to the updating of professional standards for workers of 3-4 skill levels are relevant for all sectors of the national economy. In this study, we have analyzed the qualifications and training of the main participants in the labor market in the field of biomedical waste management in health care organizations, agriculture and veterinary medicine, food and biotechnology industries, food trade, hospitality sectors, tourism, as well as other organizations in which medico-biological waste is generated. The purpose of this work is to analyze the algorithm for updating professional standards for management of medical and biological waste specialists.

In the course of updating the Professional standard “Worker in the area of medical and biological waste management”, employees of the Department of Industrial Ecology of the Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation made a proposal to supplement the labor functions of this standard with new competencies and a new qualification “Specialist in medical waste management, formed in the organizations of pharmaceutical activity”.

The review highlights the advances in natural science that form the basis of the concept of personalized and precision medicine (PPM). The provisions of PPM (prediction, prevention, personalization) have been disclosed and modern molecular genetic tools have been shown, which are used in leading scientific and practical biomedical centers to improve the quality of treatment of patients with multifactorial diseases (MFD). The main principles of molecular genetic biomarking of MFDs, as well as gene technologies (CRISPR, non-coding RNA, etc.) used in medical practice and at the stage of clinical trials were highlighted. Particular attention has been paid to molecular genetic methods of targeted therapy for cancer, including antitumor vaccines. Scientific developments in the field of prediction and preventive treatment of MFD have been considered - precision healing technologies of tomorrow. The main provisions of interactomics as an interdisciplinary field of natural science have been highlighted, as well as the applied aspects of this section of fundamental science for the development of diagnostic and treatment-and-prophylactic technologies of a new generation.

The article is dedicated to the director of the Leningrad Chemical and Pharmaceutical Institute (now the Saint Petersburg Chemical and Pharmaceutical University), a specialist in the field of chemical absorbers, Viktor Nikolaevich Ivanov, who headed the university in 1951–1958. The contribution to the development of chemical science has been revealed, also the activities during the years of the defense of Leningrad in 1941–1944 have been traced. In addition to the Chemical and Pharmaceutical Institute, his teaching activities were associated with the Leningrad and Moscow State Universities. During the era of his directorship at the Chemical and Pharmaceutical Institute, he managed to significantly strengthen the teaching staff, including specialists in the humanities, the famous sociologist I. S. Kon, as well as construct a new building and create a medicinal plant nursery in Lembolovo.