Vol 26, No 9 (2023)

Relevance. Natural killer (NK) cells are considered to be effective cytotoxic cells of the tumor microenvironment, whose function is to effectively eliminate tumor cells. Their activation can occur when the NKG2D receptor interacts with the NKG2DL ligand expressed, for example, on tumor cells, which leads to the death of the latter.

The aim of the study was a comparative study of the content of soluble forms of the sNKG2D receptor and its ligand sNKG2DL1 in the blood serum of healthy donors and patients with colorectal cancer (CRC), taking into account the clinical and morphological characteristics of the disease and prognosis.

Material and methods. We examined 65 patients with CRC (32 women and 33 men), who were treated at the “National Medical Research Center of Oncology named after N.N. Blokhin” of the Ministry of Health of Russia aged (median 60 years) and 30 healthy donors (20 women and 10 men) aged (median 47 years). The clinical diagnosis in all patients was confirmed by the data of the morphological study of the tumor according to the International Histological Classification of Tumors of the Digestive System (WHO, 2019), all had adenocarcinoma. The concentration of NKG2D and NKG2DL proteins was determined by ELISA in blood serum before treatment with Human B7-H3 Quantikine ELISA Kit reagents firm R&D (USA) in accordance with the manufacturer's instructions. The measurements were carried out on an automatic enzyme immunoassay analyzer BEP 2000 Advance (Siemens Healthcare Diagnostics, Germany). Statistical analysis of the obtained results was carried out using GraphPad Prizm v. 9. Overall survival analysis was performed by constructing survival curves using the Kaplan-Meier method.

Results. In patients with colorectal cancer, a significant increase in the content of sNKG2DL in blood serum was found compared to the control group. sNKG2D concentrations did not differ between controls and CRC patients. No significant associations were found between the content of sNKG2D and sNKG2DL1 proteins in the blood serum of CRC patients and the main clinical and morphological characteristics of the disease. A decrease in the concentration of sNKG2D was noted with the progression of the disease, and the highest content of sNKG2D was found in the localization of the tumor in the caecum. For the ligand sNKG2DL1, the opposite pattern was observed, namely, its lowest concentration in blood serum in tumors located in the caecum. For the ligand sNKG2DL1, the opposite pattern was observed, namely, its lowest concentration in blood serum in tumors located in the caecum. At the same time, the levels of sNKG2D and sNKG2DL1 in the control group directly and significantly correlated with each other (r=0.453; p=0.014), while no such pattern was found in the group of CRC patients (r=-0.014; p=0.935). sNKG2DL1 concentrations are not a prognostic factor in CRC, while high levels of sNKG2D tended to lead to a favorable prognosis of the disease, which indirectly confirms the positive significance of tumor infiltration by NK cells.

Conclusions. The mechanisms of the relationship between CRC avoidance of immune surveillance and the expression of the sNKG2D receptor and the sNKG2DL ligand are discussed as one of the directions in the study of immune checkpoints. We believe that the effect of CRC immunotherapy can be achieved by increasing the expression of NKG2D on immune cells and inducing the expression of NKG2DL in tumor cells, which is the basis of the concept of this line of research.

Relevance. The relevance of the antimicrobial peptides study is justified by the serious problem of antibiotic resistance, which presents a worrisome prospect of a significant number of deaths and economic losses in the future. In recent years, scientists have increasingly focused on natural substances, such as antimicrobial peptides, which do not induce bacterial resistance and may be safer for the human body compared to antibiotics.

Aim of the research. This review article aims to structure the scientific literature on exploring the potential applications and generation of peptide complexes from the human body.

Material and methods. The following databases were used for information retrieval: PubMed, American Society for Microbiology, ResearchGate, Frontiers Research Foundation, Public Library of Science, BioRxiv, Nature Communications, European Commission.

Results. The paper provides a description, structure, history of discovery, and research on antimicrobial peptides derived from the human body. The biological properties of these peptides are outlined. The prospects for further studying their properties and developing new-generation antibacterial drugs from them are presented.

Conclusions. The investigation of human antimicrobial peptides and the development of innovative drugs based on them represent a promising direction in modern biotechnology. The systematic analysis of scientific data regarding the possibility of obtaining and utilizing peptide complexes from the human body signifies a significant step in the development of novel and effective antimicrobial drugs capable of overcoming the growing threat of antibiotic resistance and aiding in the fight against infectious diseases.

Relevance. One of the most common and popular reference samples used as reliable standards is retinol palmitate – vitamin A, which is widely used both in the food industry and in veterinary medicine, but this sample is especially popular when analyzing pharmaceutical products. However, this valuable object still needs to implement a number of technological solutions, primarily related to the technology of its production from domestic natural raw materials, taking into account the extremely significant resource-saving factor today. For the first time, a species of fish successfully grown and cultivated in Russia – the salmon family – trout, as well as a representative of the flounder and mackerel breeds that are not cultivated, but exist in Russia, are considered as raw materials.

This article discusses a method for obtaining the substance of vitamin A, which is actively used in pharmaceutical production. There are several known ways to obtain fat-soluble vitamin A both from natural raw materials and by synthesis. The article examines technological approaches with the use of innovative measures that increase the production attractiveness of the developed technological approach (technological scheme). The originality of these studies is based on the use of resource-saving technologies in the production of fat-soluble vitamins, which reduce the consumption of materials (reagents), labor and energy costs, by reducing the time for the main technological stage, as well as the possibility of using the resources of domestic enterprises for processing cultivated and wild fish species as a raw material base.

The purpose of the work. To propose an original technology for obtaining vitamin A substance (retinol palmitate) using the domestic fish raw material base, and to identify and standardize the result obtained.

Material and methods. The main object of the study is the type of fish actively grown on the territory of the Russian Federation. The main factors determining the choice of the object were such characteristics as the availability of the raw material base, the high fat content in the object and the relatively low cost of raw materials.

In the production process, innovative methods of obtaining and cleaning the final product were also used, such as oxygen-free technological operations using the microwave exposure method.

The identification of vitamin A in the samples was carried out using UV spectrometry, which confirmed the validity of the selected raw material object.

Results. The use of innovative methods for isolating the substance from fish products using the effect of microwave decomposition of biological material in an inert gas environment has reduced the time of the main stage of production from an average of 180 minutes to 30.

The production of substances from natural materials makes it possible to obtain a cleaner and, as a result, a more physiological product that does not require complex purification steps and does not have toxic micro-impurities in its composition.

The developed method of obtaining vitamin A substance will make it possible to replenish the material base, which should exist as a constantly replenished resource. Special attention should be paid that the vitamin A substance can be used not only as a pharmaceutical substance, but can also find its application in the veterinary and food industries as a biologically active additive (dietary supplement) and as a reference material - a standard sample (CO) for use in analytical practice (conformity assessment) and scientific research.

Conclusions. Thus, for the first time, an original technology was developed for the production of retinol palmitate from natural domestic raw material – fish belonging to breeds cultivated in Russia. The optimal technology has been developed taking into account the resource-saving factor. In the process of technology, such innovative technological techniques as the use of oxygen-free grinding of raw materials, microwave radiation during hydrolysis, the implementation of all technological stages in an inert gas environment have been developed.

Relevance. Due to the wide spread of diseases of the cardiovascular system, the development and study of drugs aimed at the treatment of diseases of the circulatory system is relevant. A new biologically active compound (BAC) is synthesized at the Department of Pharmaceutical and Toxicological Chemistry of the Volgograd State Medical University – a derivative of quinazoline: N-[2-[4-oxo-3(4H)-quinazolinyl] propionyl]-guanidine (VMA-13-15), which at the stage of preclinical studies confirmed the prospects for use in medical practice as a cardioprotective and neuroprotective drug.

The aim of the study is to develop and validate a method for the quantitative determination of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]-guanidine (VMA-13-15).

Material and methods. The objects of study are laboratory samples of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]-guanidine (VMA-13-15, series 2019, 2020 and 2021). A laboratory sample VMA-13-15 twice recrystallized from methanol and dried to constant weight is used as a standard sample (RS). Quantitative determination is carried out by acid-base titration in a non-aqueous medium. The end of the titration is fixed potentiometrically.

Results. The ionization constants VMA-13-15 are determined. A procedure is developed for the quantitative determination of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]guanidine by acid-base titration in a solvent medium of glacial acetic acid with the establishment of an equivalence point using a potentiometer. The developed method is validated according to the main characteristics: specificity, linearity, correctness, convergence and analytical area. The validation analysis of the developed method confirms that it is suitable for the quantitative determination of the main substance content in the VMA-13-15 substance.

Conclusions. A technique for potentiometric titration of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]guanidine in a non-aqueous medium is developed and validated.

Relevance. Silver nanoparticles are interesting as an alternative to antibiotics and as their carrier. Bioavailability of silver is affected by particle size, morphology, and concentration. The studied combination of methods is promising for the rapid detection of technological defects in production and the fight against counterfeiting.

Objective. To develop a combined method for quality control of silver-containing colloidal solutions. This method in addition to elemental determination will consider the disperse characteristics of particles.

Material and methods. Four silver-containing preparations were studied: ProtargolLor (P.J.S.C. “Pharmstandard”, Kursk); Argitos colloidal silver (“Nanosphere”, Russia), Argent Colloidal (Nutri expert, France); Granions d’Argent (Laboratoire des Granions Le Mercator, France). The study was carried out using Energy dispersive spectrometer Shimadzu EDX-7000 (Japan), Laser hydrodynamic particle size analyzer Zetasizer (Malvern Instruments, UK).

Results. In this article we propose the use of a combined method for the quality control of silver-containing preparations. The express X-ray fluorescence method is supplemented by the method of dynamic laser light scattering. This combined method allows to determine the composition and size spectra of the particles of the studied samples. It will significantly reduce costs and protect the laborants from the toxic effects of reagents used for mineralization.

Conclusion. The combination of disperse and elemental analysis methods is promising for quality control of silver-containing pharmaceuticals. This technology will detect counterfeit and manufacturing defects.

Relevance. One of the time-consuming stages on which the success of clonal micropropagation depends is the transfer of microclones from in vitro conditions to ex vitro conditions. At this stage, plants experience stress, which leads to their death. In addition, the low survival rate of plants to ex vitro conditions is primarily due to their poorly developed root system, non-functional stomatal apparatus, poorly formed cuticle, as well as the use of non-sterile soil. The effectiveness of clonal micropropagation depends on the choice of the nutrient substrate and the technology of adaptation of microclones to ex vitro conditions. Hydroponic and aeroponic technologies are designed to increase the productivity and economic efficiency of clonal micro-propagation of plants, by reducing the time of cultivation of cloned plants.

Purpose of the study. The aim of the study was to study the effect of aeroponics on the growth and accumulation of phenolic compounds in the microclones of medicinal plants Mentha piperita L. and Melissa officinalis L.

Material and methods. The object of the study was the microclones Mentha piperita L. and Melissa officinalis L., which were originally propagated on a hormone-free nutrient medium containing mineral salts according to Murashige and Skооg (MS). Microclones were adapted to ex vitro conditions in two ways: on an aeroponic installation and directly in the soil. Adaptation was carried out on two groups of plants: 1 – with roots, 2 – without roots (the root system was removed with a scalpel before planting on an aeroponic installation or in the soil). The results were taken into account at the end of the adaptation cycle, while taking into account the length of the root system (cm) and the height of plants (cm). Based on the results obtained, the growth index (I) and the specific growth rate (µ) were calculated, and the total content of phenolic compounds and flavonoids was determined.

Results. It is established that at the last stage of clonal micropropagation, it is advisable to use aeroponic installations that allow rooting and adaptation of microclones simultaneously. The developed method makes it possible to obtain high-quality planting material, since this reduces the percentage of plant death, increases the growth and development of green biomass, as well as the root system. The rooting of micro-shoots during adaptation is achieved by including in the composition of the nutrient solution of IBА at a concentration of 0.5 mg / l. In addition, under these conditions, there is a change in phenolic metabolism, which manifests itself in an increase in the total content of phenolic compounds in microclones.