This work is aimed at developing and studying the antitumor action of a clathrate complex of a rhodanine derivative (RD) of the 3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one compound with β-cyclodextrin. In terms of physicochemical and biopharmaceutical properties, the RD clathrate complex with β-cyclodextrin with a mass ratio of 1:5 and an average particle size of 40.5 nm is a promising pharmacologically active drug. The developed RD clathrate complex with β-cyclodextrin exhibits a pronounced antiproliferative and antimetastatic effect against epidermoid Lewis lung carcinoma tumors. RD as part of a clathrate complex with β-cyclodextrin enables effective inhibition of tumor growth and metastatic processes, increasing the average life expectancy of animals, reducing the number of metastases in the lungs, and suppressing cell viability in an MTT assay. The results obtained confirm the feasibility of further research into the RD clathrate complex with β-cyclodextrin as a means for treating oncological diseases caused by hyperexpression of GSK-3β both as an independent agent and in a combination therapy with other antitumor agents. Due to its physiological safety, the RD clathrate complex with β-cyclodextrin is a promising antitumor agent for practical application.

Removal of the N-terminal initiator methionine (Met1) affects 50–70% of cellular proteins, being an important post-translational modification. This modification is catalyzed by such specific enzymes as methionine aminopeptidases (MAP). Recombinant MAPs from E. coli and humans are used in scientific research, as well as in biotechnology to remove Met1 from recombinant proteins under their heterologous overexpression in E. coli. Differences in substrate specificity and operating conditions of known MAPs warrants the search for new enzymes capable of operating at elevated temperatures. We cloned an MAP from a hyperthermophilic bacterium, developed a method for purifying the enzyme, and studied the activity of the enzyme in a wide temperature range. We show that the MAP from Thermus thermophilus is most active at temperatures from 75 to 95°С. The new enzyme can be used to remove N-terminal methionine from recombinant proteins in vitro at elevated temperatures.

There exist numerous local hemostatic agents; however, their disadvantages, such as a short shelf life, high cost, lack of antiseptic properties, a single mechanism of action, residual toxicity, etc., require the development of new materials capable of meeting as many requirements for an “ideal” hemostatic as possible. Meanwhile, regardless of the mechanism of injury, the implementation of hemostasis is of crucial importance for eliminating the consequences of acute bleeding until the provision of the necessary medical care. This article discusses the safety and effectiveness of some of the most promising local hemostatics, in particular, those created from chitosan and kaolin.

The application of Langmuir technology for analyzing free fatty acids makes it possible to obtain monolayers consisting of barium monocarboxylates, while the characteristic isotopic distribution of barium makes it possible to simplify the identification of compounds containing this element in mass spectra. The formation of monomolecular Langmuir films directly on the surface of the matrix-assisted laser desorption/ ionization of the target, reduces and simplifies sample preparation, at the same time as increasing the sensitivity of the technique for profiling of free fatty acids in biological samples of different origin.

The tumorigenic potential of A172, U251, and U87 glioblastoma cells has been studied in mice of the NODscid line.

A series of studies performed on 29 male Wistar rats found that food deprivation for 9 days with free access to water is accompanied by a loss of 24% in body weight, while causing hypertrophy of the adrenal glands and involution of the thymus. At the same time, gradual changes in the indicators of protein, carbohydrate, and fat metabolism were observed, associated with changes in energy substrates.

Despite the success in creating genetically modified animals with improved economic characteristics, immunological biotechnologies represent an alternative, more conventional and safer, approach to increasing the meat productivity of farm animals. For example, animals with a knockout of the MSTN gene have not only overly developed muscles, but also serious health and reproduction problems. Blocking the action of endogenous myostatin by immune methods in the phase of intensive animal growth may become a hightech and safe method for effective animal husbandry. Currently, purified recombinant proteins and peptides with a low intrinsic immunogenicity are increasingly used as antigens for immunization. The effectiveness of the created vaccines depends not only on the antigen used, but also on the methods of its administration, adjuvants, and the type of animals, being determined, as a rule, empirically. We obtained a recombinant myostatin (rMST) producing strain; the protein was used as an antigen in a composition with various adjuvants to determine its immunogenicity. The obtained rMST, along with aluminum hydroxide gel as an adjuvant, was used as a vaccine to immunize four-month-old lambs. It was shown that a single subcutaneous multipoint immunization at a dosage of 1 mg rMST per head led to a noticeable immune response and an increase in body weight.

In order to ensure adequate nutrition of musk deer in captivity, it is essential to have data on the digestibility of feed nutrients. In this work, we carry out an indirect assessment of the digestive characteristics of captive musk deer in the autumn and winter periods. The influence of age, gender, physiological state, and seasonal changes on nutrient excretion is analyzed. The most sensitive parameter was found to be mineral metabolism, phosphorus metabolism in particular. Other unstable parameters include excretion of fiber, fat, and protein. The results obtained provide information on the digestibility of feed and justify the need for balancing feedings for different age and sex groups of musk deer kept under farm conditions.

Immuno-biotechnological methods for increasing the meat productivity of farm animals may be in demand for effective animal husbandry. Currently, recombinant proteins and peptides are increasingly used as antigens for immunization purposes. Previously, we obtained a strain-producer of recombinant myostatin. The protein was developed, purified under denaturing conditions and, in a composition with aluminum hydroxide gel, rMST was used as a vaccine for immunization of four-month-old lambs. The effect of the vaccine administration method on the live weight gain of lambs was investigated. It was shown that onetime subcutaneous multipoint immunization of four-month-old lambs with rMST at a dosage of 1 mg/head in aluminum hydroxide gel as an adjuvant was more effective than intramuscular vaccination in stimulating body weight gain.

Salmonella enteritidis (SE), referred to nosocomial infections, colonizes the intestines of chickens and pigs. This leads to food contamination and increased risk of pathogen transmission to humans along the food chain. Multidrug-resistant (MDR) SE strains are particularly dangerous for newborn children and young farm animals. The antibiotics traditionally used for the treatment of salmonellosis disturb the balance of the intestinal microbiota. The development and use of synergistic synbiotics is a promising preventive direction in limiting the spread of salmonella infection. Synergistic synbiotics combine prebiotics and probiotics, which thus function optimally. The role of synbiotics in the prevention of SE remains to be elucidated. The aim of this study was to create a synergistic synbiotic with bactericidal activity and anti-adhesive properties against salmonella. As a result of the conducted research, an innovative synergistic synbiotic was created. This preparation comprises a consortium of probiotic strains of lactobacilli L. fermentum 3872 + L. salivarius 7247 and the Actigen prebiotic (a fragment of the cell wall of S. cerevisiae). In vitro experiments revealed that the consortium has a pronounced bactericidal effect on MDR SE. The culture fluid of the consortium, together with the Actigen prebiotic, is active and exhibits synergistic anti-adhesive properties against MDR SE. Further studies will apply the results obtained for developing a protocol for preclinical studies of the created symbiotic in vivo on experimental animals.

Three experimental models suitable for screening first aid medications for seizures of obscure etiology are developed. Hypobaric exposure in a pressure chamber at an “altitude” of 12 km, intraperitoneal administration of a 50% N-methylpyrrolidone solution of camphor in a volume of 2 ml/kg, or an aqueous solution of ammonium acetate in a dose of 770 mg/kg were used to induce convulsions in rats. Seizure latency time and lethality are proposed as necessary and sufficient criteria for assessing the effectiveness of tested pharmaceuticals. The developed models make it possible to evaluate the efficacy of potential anticonvulsants in the mode of emergency prevention or seizure relief. Due to the versatility of the neurotoxicity pathways of the convulsive agents, these experimental models are suitable for identifying anticonvulsants that are effective in convulsive syndrome of obscure etiology.

The article presents the results of including hydrogen-rich water in the diet of Chinchilla lanigera (longtailed chinchilla). The experiment was carried out on two groups of chinchillas: control (n=10) and experimental (n=10). The long-term scientific experiment covered the period of three years. At the beginning, in to determine the toxic effects of molecular hydrogen. To that end, laboratory investigations were conducted to assess the morphometry of the renal capillary glomeruli, characterizing the vascular bed, and to determine the area of hepatocytes, their nuclear-cytoplasmic ratio, as well as the stromal and parenchymal components of the liver. The long-term use of hydrogen-rich water was shown to contribute to a decrease in the area of the renal glomeruli of animals in the experimental group by 27% (p<0.01). In addition, an increase in the parenchymal component of the liver and the volume of cytoplasm in hepatocytes (p<0.01) was observed. It is concluded that the inclusion of hydrogen-rich water in the diet of animals has a beneficial effect on the condition of the renal glomeruli and vascular system and has no toxic effect on the liver.

Musk is a dried secretion of the preputial gland of musk deer, widely used since the middle of the 4th century as a biostimulant in traditional Arabic, Indian, Tibetan, and Chinese medicine. Currently, within the transition to evidence-based medicine, relationships between the composition of musk and its pharmacological properties is being studied. Musk is a multicomponent system consisting of substances of different classes, the content and relative amounts of which are directly affected by the technology of musk extraction. The development of a new method – electropulse extraction – significantly increased the yield of the extract and affected the composition of musk by increasing the relative content of the peptide-protein fraction. This ensured the emergence of new properties of musk, namely the property to increase physical performance while increasing the safety of physical activity by suppressing the state of inflammation and oxidative stress associated with extreme stress. In general, progress in the development of new deer musk-based drugs is associated with technological innovations in this industry. 

Selection of an optimal general anesthesia regimen is an essential prerequisite for the conduction of electrophysiological tests in laboratory animals. In this work, we compared the effects of two general anesthetic drugs commonly used in preclinical studies, i.e., chloral hydrate (CH) and tribromoethanol (TBE), on the parameters of neuromuscular function in outbred mice. CH and TBE were found to distinctly affect peripheral nerve conductivity and skeletal muscle contractility recovery following electrical stimulation-induced fatigue.

The article presents the results of studying the parameters of the cardiovascular system (CVS) in rats under conditions of ischemic-reperfusion simulation and exposure to electromagnetic radiation of extremely high frequency (EHF EMR). The aim was to identify changes in CVS parameters in rats during the postischemic period following preventive EHF exposure.
The experiment was carried out on 30 mature male Wistar rats weighing between 200 and 220 g, which were housed in a vivarium under a natural light-dark schedule. Using a modified block randomization method, the animals were split into three groups with 10 rats in each: group 1 included sham-operated (SO) animals, which underwent surgery according to the operation plan but without occlusion of the left carotid artery; group 2 included truly operated animals who underwent surgery and had the left common carotid occluded (CCO) in accordance with the plan; and group 3 (EHF) included animals that underwent preventive 10-fold action of low-intensity EHF EMR followed by ischemia-reperfusion modelling (on the 10th day, after 60 min after the 10th session of EHF exposure) and OCA occlusion.
It is shown that the modelled ischemia-reperfusion of the brain is associated with a strain of the physiological reserves of the CVS and the body as a whole. Thus, an increase in systemic blood pressure, heart rate, sympathetic effects on the CVS, energy costs, and oxygen consumption by cardiomyocytes is observed. Recovery of CVS indicators to the level of SO is observed on the 3rd day after ischemia.
It was found that preventive 10-fold exposure to EHF mitigates the effect of ischemia, which is reflected in a decrease in all CVS indicators (except for PP). This increases adaptive capabilities of the body and accelerates recovery in post-ischemia, as well as promotes faster adaptation of physiological reserves to ischemic damage.

The progressive development of diabetes mellitus (DM2) in db/db mice is associated with three stages of impaired carbohydrate metabolism and redox processes. In db/db mice, the content of erythrocytes, hemoglobin, and leukocytes was found to decrease already in stage I of DM2. In the II and, in particular, III stages, an increase in platelets, percentage of neutrophils, monocytes, and eosinophils was observed, along with a decrease in lymphocytes. In the bone marrow of db/db mice, a decrease in the proportion of living cells and an increase in the number of damaged cells were determined already in stage I, but especially in stage III, mainly due to aponecrotic cells. Therefore, along with the progression of DM2 and a marked decrease in the effectiveness of redox processes, particularly in stage III, hematopoiesis processes are inhibited and disturbances in the ratio of neutrophil/lymphocyte cell populations increase. This indicates the development of severe hypoxia, activation of a systemic inflammatory reaction, and inhibition of reparative processes that create conditions for the development of dangerous complications.

Experiments conducted on 10 male Wistar rats established various adaptive reactions of the rate of blood flow in the stomach and jejunum of hungry and well-fed animals to a stress state modelled by hypothermia. During the period of maximum body cooling (below 32°C), in hungry and well-fed animals, the rate of blood flow in the stomach showed no significant changes. In the jejunum, the rate of blood flow in hungry animals tended to slow down, while it increased significantly in well-fed animals.

In this study, we consider problematic issues associated with harmonization of pharmacopoeial approaches to the assessment of the main physicochemical indicators of immunobiological medicinal products in the context of formation of a regulatory system of the Euro-Asian Economic Union (EAEU) with the purpose of ensuring the independence of the pharmaceutical market of the Russian Federation. Among the selected quality indicators of human immunoglobulin preparations, which are used in national and international pharmacopoeial standards, were selected the following: “Protein”, “Electrophoretic homogeneity”, and “Molecular parameters”. “Thiomersal”, “Phenol”, and “Aluminum” were selected to assess the quality of vaccines and anatoxins.
The harmonization of the above methodological approaches to the assessment of a particular indicator is hampered by the historically evolved differences in the requirements and recommendations of the State Pharmacopoeia of the Russian Federation and the European Pharmacopoeia, recognized as the basis for the development of harmonized requirements of the EAEU pharmacopoeia. These differences relate to methodologies, standards for a particular indicator, and approaches to their metrological support (use of appropriate reference materials). In the course of the study, a comparative analysis of these differences was carried out. The tendency of most manufacturers to switch to the use of high-tech laboratory equipment based on high-performance liquid and/or gas chromatography and atomic absorption spectrometry is noted. Information on the development of these methods and the availability of appropriate reference materials is provided. The conducted comparative analysis indicates the relevance of the development and certification of pharmacopoeial reference materials for harmonized methods of determination of protein, electrophoretic homogeneity, and molecular parameters. Approaches to extending the application range of available pharmacopoeial reference materials are shown, taking into account the potential of improved methods of quality control of vaccines and anatoxins by quantitative content of preservatives and adjuvants. The Russian laboratory pharmaceutical practice is focused on the specifics of immunobiological preparations and the use of pharmacopoeial reference materials that enable intra- and inter-laboratory quality testing.

This study examined the effect of peptide extracts from the epiphysis-pituitary gland of reindeer (Rangifer tarandus) and delta-sleep-inducing peptide, simulating modified release, on the physical performance of male rats under conditions of light desynchronosis. All tested agents had a positive effect on the physical performance of male rats, increasing the duration of the first and second swim, depending on the lighting regime and the degree of desynchronization. In addition, the effectiveness of the tested agents was also noted after a course of intranasal administration (formed light desynchronosis), which indicates their prolonged action. This method of pharmacological tuning of the body’s circadian oscillators by agents of a peptide nature with a modified release can be used to develop a scheme for correcting light desynchronosis.

The study of decompression sickness in animals is an important area of research in the field of hyperbaric medicine. Decompression sickness is a serious condition that can occur in humans when there is a sudden transition from high-pressure conditions, such as when diving deep into water, to low-pressure conditions, such as when surfacing. Understanding the mechanisms of the onset and development of this disease in animals can help improve prevention and treatment methods in humans. This study examined different decompression rates during 60 and 30 min of exposure aground, determined the incidence of decompression sickness in animals and the survival rate.

Arterial gas embolism can result from complications related to medical and surgical procedures, as well as a direct entry of air into the systemic circulation due to the disruption of the alveolar-capillary barrier. Since air in the arterial circulation can lead to organ ischemia, this life-threatening pathology requires prompt intervention. In this study, we demonstrated the effectiveness of using a hyperoxic heated helium-oxygen mixture in cerebral arterial air embolism. Oxygen therapy under normobaric conditions did not affect the outcome of arterial air embolism. A continuous inhalation session for 30 min, or intermittent inhalation sessions 3 times for 5 min each, eliminated foci of ischemic stroke in rats.

The mechanisms of hypoxia development at various levels – from molecular and cellular to organ and systemic – continue to attract research attention. At present, the pathogenetic demonstration of a new principle of pharmacological correction of metabolism and dysfunction in hypoxia seems relevant. In this work, hypobaric and hemic hypoxia is modeled, and the main markers for assessing the condition of animals are identified. Animals from the model group showed statistically significantly lower results in behavioral tests, which confirmed the success of modeling. The tested model and the markers for assessing the condition can be used to determine the antihypoxic effect of active medicinal substances.

In this paper, we study the hypoglycemic activity of the 4,4'-(propanediamido)dibenzoate sodium (maloben) pharmaceutical substance in combination with metformin, an antidiabetic drug of the biguanide class, and empagliflozin, an inhibitor of sodium-dependent glucose transporter type 2 (SGLT2) in the kidneys, in the setting of a streptozocin model of diabetes mellitus in combination with a high-fat diet in laboratory outbred male rats. The use of a high-fat diet makes it possible to simulate the state of prediabetes and increase the effectiveness of streptozocin administration. Streptozocin increases the level of glucose in the blood and urine of animals, as well as that of diuresis, which indicates the development of a pathology similar to actual type 2 diabetes mellitus. As part of the study, the dynamics of changes in glucose in the blood and urine, daily diuresis, and body weight of animals were analyzed.

Diabetic neuropathy in type 2 diabetes mellitus is one of the most common microvascular complications. Uncontrolled hyperglycemia leads to the formation of vascular abnormalities, eventually causing ischemia of nerve fibers. In our experiment, C57BL/6 mice were maintained on a high-fat diet for 21 weeks. At week 17, 19, and 21, blood glucose concentrations were measured; functional testing was performed using von Frey filaments, hot plate and limb cooling with acetone. In the present study, C57BL/6 mice on a high-fat diet showed increased sensitivity to mechanical stimulus, limb cooling and heating, which may indicate the development of diabetic polyneuropathy.

In this research, we develop a tissue-engineered product (TEP) based on chondrocytes of various genesis in the form of 3D structures (chondrospheres) after subcutaneous implantation in immunodeficient Balb/c Nude mice and investigate its biodistribution profile. Initially, chondrospheres based on chondrocytes and chondrocytes from differentiated induced pluripotent stem cells (iPSCs), including lines with a knockout of the β2m gene, were implanted. The animals were monitored for nine months. Further, after euthanasia, organ and tissue samples were obtained for histological analysis, evaluation of the viability of the implant, its integration and biodistribution research by PCR. Chondrospheres from differentiated iPSCs derivatives of both types successfully integrated into the surrounding tissues in the inoculation zones and formed cartilage tissue. In the samples near the implantation zone of the experimental groups of animals, no human DNA was detected. Human DNA was found in the samples of organs of the control groups (introduction of MDA231 and mesenchymal stem cells). Thus, three and nine months after implantation, the studied TEP samples demonstrated the absence of biodistribution to other tissues and organs of mice, which indicates the safety of the drug being developed.

The development of an adequate biomodel of a pathological condition, comparable to the observed clinical case, remains an urgent problem. In order to study the analgesic and anti-inflammatory activity of potential pharmacological substances, it is important to develop inflammation models with signs of cartilage tissue degeneration and pain induced by inflammation. This extends the capabilities of modern approaches. In this work, a model of arthritis induced by monoiodoacetate (MIA) (Sigma-Aldrich, USA) was carried out on rats. To that end, 3 mg of MIA in 50 μl of sterile saline solution was administered intra-articularly into the right knee joint. The model was verified using standard therapy with non-steroidal anti-inflammatory drugs (meloxicam, ibuprofen), which were administered daily from day 3 to day 14 after MIA. Inflammation and behavioral changes associated with pain were assessed on days 3, 7, and 14. On days 8 and 15, the rats were euthanized, and biological material (blood and right knee joint) was collected for histological analysis. The concentration of IL-1β in the synovial fluid was measured on days 8 and 15 after MIA administration to the knee joint of the rats. A single administration of ibuprofen had a pronounced analgesic activity, preventing disability and not weakening the grip strength of the paw into which MIA was administered. At the same time, the selective inhibitor of cyclooxygenase meloxicam was only capable of reducing mechanical hypersensitivity in a von Frey test. Therefore, the effects of a single and course administration were highly similar in terms of the level of influence in pain tests. However, regular administration of cyclooxygenase inhibitors reduced joint inflammation more effectively than a single dose. Meloxicam showed a higher efficiency than ibuprofen in reducing joint inflammation. The results are shown after histological analysis of the knee joint injected with MIA. Thus, a model of osteoarthritis induced by MIA in laboratory animals was developed and characterized.

The article presents the results of reproduction of the cyclophosphane model of heart failure. Outbred mice weighing 18–26 g at the onset of the experiment were used. All mice were divided into two groups with 10 animals in each. The first group was injected intraperitoneally with cyclophosphamide at a dose of 15 mg/kg, five times for 21 days (day 1, 5, 10, 15, and 21). The second group was intact animals. EchoCG was performed on the animals twice: baseline before the experiment (point 1) and one week after the last injection (point 2, day 28). The presented experimental model may be used for the study of drug toxicity prevention methods, as well as a model of heart failure with preserved left ventricular ejection fraction.

The cardiotropic activity of etmaben, a malonic acid derivative, has been confirmed by a number of studies. The possibility of using empagliflozin in chronic heart failure has been proven in a number of preclinical and clinical studies. In this study, the efficacy of the drugs in monotherapy and combined use regimens is compared using a model of experimental chronic heart failure in rats. The most effective treatment regimen was found to be etmaben; its combination with empagliflozin led to a decrease in effectiveness, regardless of which of these drugs was the starting drug.

The absence of a generally accepted model of gestational diabetes makes the task of its search and development highly relevant. The conducted experiments found that a high-calorie diet in combination with tyloxapol administration in various modes in the second half of pregnancy of Wistar rats leads to impaired glucose tolerance, an increase in the level of DNA damage in the organs of offspring, and deviations in the postnatal period of development. The proposed model can be used to search for pharmacological correction of reproductive disorders in gestational diabetes.

The present study was aimed at exploring the pathomorphological changes in liver and skeletal muscle tissue in C57Bl/Ks-db⁺/⁺m (db/db) mice of different ages. The study was conducted in female db/db mice aged 3 (n=7) or 7 months (n=5). According to the results of histomorphological examination, no significant differences were found between the groups.

TRPV1, which plays a key role in transmitting pain signals, is widely distributed in various tissues and cells, including the central nervous system. Activation or suppression of TRPV1 influences neuronal desensitization, pain signal transmission, and regulation of neurotransmitter systems. The APHC3 peptide, as a selective antagonist of TRPV1, is used to investigate the effects of blocking this channel in terms of anxiety and stress response in mice. The results of studies can indicate the influence of TRPV1 on the formation of emotional states. This study is important for understanding the impact of TRPV1 channels on stress in ICR mice, being promising for further research in the field of biomedicine and biomodeling.

This work shows that age-related arterial hypertension in Wistar rats develops with age, in 52% of 18-monthold animals versus 33% of 3-month-old animals. Effects of Taxifolin at a dose of 100 mg/kg, administered intraperitoneally for a week, on blood pressure (BP) and biochemical parameters in 18-month-old and 3-month-old animals were studied. The experimental animals were divided into two groups, those normotensive (BP<115 mmHg) and hypertensive (BP>115 mmHg). It was shown that a weekly course of Taxifolin leads to a significant decrease in blood pressure in hypertensive 18-month-old animals with no effect on blood pressure in normotensive animals. In addition, some age-related changes in the biochemical parameters of blood under the influence of Taxifolin were revealed.

The article presents the results of a research study into the effectiveness of hydrogels containing calcium complexes and/or ionomers based on copper (II) complexes on the healing rate of a wound surface formed by a thermal burn.

The survival of mice was determined 30 days after exposure to protons, carbon ions, or X-rays in the presence and absence of xylazine-zoletil anesthesia. The anesthesia used was shown to increase the lifespan of mice during the specified period for photons and most applied doses of protons and carbon. The maximum effect of anesthesia was observed when irradiated with carbon ions (by 3.3 times), with protons (by 1.7 times), and with X-ray radiation (by 1.7–2 times), which should be taken into account when selecting doses. This indicates the specificity of the combined effect of anesthesia and the physical characteristics of radiation.

The beneficial effect of polyphenol resveratrol (RES) on liver diseases, including non-alcoholic fatty liver disease (NAFLD), has been reported in numerous studies. De novo lipogenesis in the liver is considered as one of the possible molecular mechanisms for the development of obesity and NAFLD. This work aimed to study the effect of RES on the development of NAFLD and to evaluate the expression of carbohydrate and lipid metabolic key enzymes genes in rats fed on a high-fat high-fructose diet (HFHFrD). For 10 weeks, the control group of Wistar male rats received a standard diet and water; three experimental groups were fed on HFHFrD. The rats in the 2nd and 3rd experimental groups received RES at a daily dose of 10 and 100 mg/kg body weight, respectively. A histological examination of the liver was carried out and the expression of carbohydrate (Khk, Gck, Pklr) and lipid (Acaca, Fasn, Scd) metabolizing enzymes and transcription factors (Mlxipl, Srebf1, Ppara) genes was studied. The consumption of HFHFrD led to the development of NAFLD, accompanied by an increase in Gck gene expression, a decrease in Pklr, Acaca, Fasn, Scd. RES in both doses had no effect on the development of NAFLD, as well as on the expression of the studied genes.

TRPV1, a key mediator of nociceptive signaling, is widely distributed in various tissues and cells, including the central nervous system. The regulatory activity of TRPV1 affects neural desensitization, pain transmission, and neurotransmitter systems. The use of the beneficial peptide APHC3 as a selective antagonist of TRPV1 is a method for studying the blocking of this channel at the level of anxiety and is a response to stress in mice. The findings improve our understanding of the influence of TRPV1 on the moderation of emotional states. This study has important implications for understanding the effects of TRPV1 on stress states in ICR mice and may also contribute to medical and biomedical research.

The study of β-amyloid peptide (Aβ) interactions with protein and peptide ligands is a relevant research task. Aβ complexes with drugs that are considered as promising candidates for the therapy of Alzheimer’s disease are of particular interest. This category includes a group of hypoglycemic drugs, such as insulin detemir, a long-acting insulin analogue. In this work, the method of biolayer interferometry is used to obtain the kinetic and equilibrium parameters of interaction of insulin detemir and monomeric Aβ forms with a chain length of 40 and 42 amino acids. A model of “insulin detemir–Aβ40/42” complexes is proposed. The data obtained can be used to study the mechanisms of the effect of insulin detemir on cognitive functions of patients with Alzheimer’s disease.

Concomitant therapy is an integral part of modern approaches in treating cancer patients, which allows the symptoms of malignant neoplasms to be mitigated and the adverse events of the treatment to be avoided. Therefore, the search for new drugs for supportive therapy of oncopathology patients seems highly relevant. Humic substances represent a promising, although insufficiently studied, group of natural compounds of plant origin. This review article is aimed at generalizing and systematizing the information currently available on the known pharmacological effects and possible action mechani

For many years, cephalosporins have been rarely reported as drugs causing hepatotoxicity. However, the recent data points to the possible development of various types of drug-induced liver damage associated with cephalosporins, including long-term ones, which manifest themselves 1–3 weeks after a single administration.

Differences in the response to pharmacotherapy with angiotensin II receptor blockers may be determined by polymorphisms in the genes responsible for their target of action. In this work, we investigate the pharmacodynamic parameters of daily blood pressure monitoring (DBPM) to assess the efficacy of therapy with angiotensin II receptor blockers in the form of monotherapy and as part of combination therapy in patients with arterial hypertension, depending on their genetic characteristics, i.e., polymorphism A1166C of the angiotensin II type 1 receptor gene (AGTR1). The study included 179 patients in the Moscow Oblast with newly diagnosed arterial hypertension of 1–2 stages. Among them, 141 (78.8%) were women and 38 (21.2%) were men aged 32 to 69 years, randomly assigned to irbesartan and valsartan groups in the form of mono- or combination therapy with hydrochlorothiazide by a simple randomization method. Following three weeks of pharmacotherapy, the presence of the rs5186 (A1166C) genetic polymorphism of AGTR1 gene was determined. DВPM was performed when patients were included in the study and after three months of therapy. The maximum antihypertensive effect was observed in heterozygotes A/C in the group of patients taking valsartan after three months of prescribed angiotensin II receptor blockers pharmacotherapy. This effect was manifested in a decreased average daily systolic blood pressure (SBP) and diastolic blood pressure (DBD), average night SBP, variability of night SBP and DBP. Among patients treated with irbesartan, there was no statistically significant association of the A1166C polymorphism genotype of the AGTR1 gene with these indicators. Heterozygotes showed a statistically significantly more pronounced decrease in the average sleeping heart rate in the group of valsartan patients. At the same time, the average daily heart rate decreased more significantly in C/C homozygotes in both the group of irbesartan and valsartan patients. Thus, when developing personalized treatment plans for patients with newly diagnosed stage 1–2 arterial hypertension using detection of the A1166C genetic polymorphism of the AGTR1 gene, it is advisable to recommend valsartan as a more effective initial therapy with angiotensin II receptor blockers in the form of mono- or combination therapy depending on the risk group for patients in the Moscow Oblast who are carriers of the A/C genotype.