Transgenic humanized mice are widely used in biomedical research for the development of new vaccines and pharmaceutical products. Specialists of the Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia have created a number of humanized mouse lines, including biomodels with an integrated human leukocyte antigen (HLA) complex. In this paper, we report a comparative analysis of the humoral immune response in mice of the HLA-A*0201 transgenic line and mice of the original line (CBA/lac × C57BL/6), F(1) hybrids) to the injected antigen – snail hemocyanin (KLH). By carrying out in vivo blood sampling from the animals of the experimental groups, the dynamics of the immune response over a period of four weeks was recorded. The titers of specific antibodies to KLH in the group of humanized mice of the HLA-A*0201 line were significantly higher than those of the original line of mice, reaching a maximum (1:51200) by the end of the experiment. The dynamics reflecting the growth of antibody synthesis as a result of repeated administration of the antigen have a similar pattern to the development of a secondary immune response in humans.

The CRISPR/Cas gene editing method and reproductive biotechnologies were used to create rabbits with a knockout of the gene for the receptor of the systemic regulator of lipid metabolism – leptin (lepr). Studies performed with clinical laboratory and functional diagnostics provided data on physiologic parameters and revealed some effects of lepr editing in the domestic rabbit. The results suggest that domestic rabbits with lepr knockout may serve as a biomedical model of morbid obesity and metabolic disorders caused by mutations in the leptin receptor gene.

The phenomenon of ultrasonic vocalization (USV) is characteristic of various laboratory animals, which are widely used in biomedical research. This phenomenon is closely linked to the functional state of animals’ central nervous system, their psychoemotional status, response to extreme stimuli, and the processes of zoosocial communication. These characteristics have allowed the introduction of USV research methods into biomedical research aimed at modeling various diseases, pathological and sanogenetic processes, and evaluating the efficacy of psychopharmacological agents. In this article, we set out to investigate the possibility of identifying the characteristics of the psychophysical state of laboratory animals using USV. A matrix for identifying the emotional states of rats based on spectral analysis of their USV is presented.

In this study, we evaluate the main hematological parameters and subfractional composition of mouse blood serum when modeling long-term hypokinesia. Hypokinesia was induced by placing the animal in a special glass and its fixation by the tail for 14 days. Hematological parameters were determined by a hematological analyzer; the subfractional composition of the serum were studied by laser correlation spectroscopy. Following 14-day hypokinesia, mice showed a significant increase in the number of neutrophils and  a decrease in the number of lymphocytes. A significant increase in the number of circulating erythrocytes was also detected. The subfractional composition of mouse blood serum after hypokinesia was distinguished by a significant increase in the contribution to light scattering of particles with a radius of 91.26 to 165.57 nm. Modeling long-term hypokinesia in laboratory animals is essential for developing approaches to the prevention and treatment of the consequences of decreased motor activity.

Oxidative stress (OS) associated with inflammatory processes affects the intestinal microbiota. Choline can act as a methyl donor and reduce the level of glutathione in the brain, inhibiting the development of OS and inflammatory processes. In turn, this contributes to prevention of dysbiotic disorders. In this work, we study the effect of choline bitartrate (CB) on the microbiota of the large intestine of pigs during the period of intensive growth. CB introduced as part of the main diet was found to affect the qualitative and quantitative composition of the  microbiota. Thus, the proportion of normoflora increased, while the proportion and representation of pathogenic and  opportunistic microorganisms decreased. CB contributed to the work of microorganisms secreting metabolites with high neurotransmitter activity and led to an increase in the proportion of phylum producers of lactate, an activator of intestinal macrophages.

Metabolomic analysis of biological samples is an important direction in the development of diagnostic methods for chronic kidney disease (CKD) in children. Hydrophilic interaction chromatography tandem mass spectrometry (HILIC–MS/MS) is widely used in metabolomics; however, this method is associated with the problem of matrix effect (ME). In this study, we evaluate the ME arising from the analysis of nine low-molecular weight polar marker metabolites of CKD under HILIC conditions in samples of new model and real urine. Amino acids and their polar metabolites involved in the pathophysiologic processes of CKD development were selected as nine biomarkers to be determined. The ME on the first quadrupole was assessed by calculating the ratio of the coelution parameters of low-molecular weight clusters consisting of buffer formate anions and salt cations in urine and L-valine-¹³C₅ standard. In real urine, the signal intensity of the L-valine-¹³C₅ standard was reduced by more than 50% relative to methanol when the cluster signal was superimposed, whereas in artificial urine, the suppression effect was comparable to the real sample under all elution conditions. The addition method was also applied to evaluate the ME of isotope-labeled endogenous markers in real and artificial matrices. It was shown that a preliminary assessment of signal quenching can be studied on model urine of a new composition. The results demonstrate the importance of evaluating the optimal signal resolution of not only marker compounds but also inorganic clusters, which can significantly reduce the analysis errors under real matrix conditions. The evaluation of this effect should improve the accuracy of polar metabolite analysis in real samples in CKD metabolomics. The applied artificial urine samples showed comparable ME to the real sample, which confirms its promising potential for optimizing the HILIC–MS/MS analysis conditions.

The search for ways to increase the meat productivity of agricultural animals is an important direction in the field of immunobiotechnology. Immunization of sheep with recombinant myostatin (rMST) led to the development of an antibody response correlating with animal weight gain. The possibility of enhancing the immunogenicity of a recombinant analogue of endogenous mature myostatin for the purpose of vaccination of young cattle was considered. A genetic construct was created for the expression of recombinant modified myostatin (rmMST), in which cysteine was replaced by serine, and the producer strain E. coli BL21(DE3)/pET-mMSTN was obtained, expressing the recombinant protein with high efficiency. Calves were immunized with rMST and rmMST twice with an interval of 30 days. Using the ELISA test system, a higher immunogenicity of rmMST was shown.

Individual differences in the effects of optical stimulation on the efficiency of sensorimotor activity depending on the anxiety level were investigated. The study involved 65 young men (aged 18–23). The trait anxiety (STAI) was assessed using the Spielberger scale; the levels of depression, anxiety, and stress were assessed using the DASS-21 scale. EEG was recorded at the initial state with eyes closed followed by calculation of the frequency and amplitude of the individual alpha-peak in occipital cortical regions. In subjects, the time of simple and complex visual-motor reaction was determined under normal conditions and under optical stimulation with the frequency of individual alpha peak plus of 2 Hz. Under optical stimulation conditions, subjects with medium trait anxiety, as well as those in the group with medium anxiety according to the DASS scale, showed a significant decrease in the complex motor reaction time, whereas no changes were observed in the other groups.

L-methionine derivatives (L-methionine sulfoximine (MSX) and L-methionine sulfone (MSO)) are  inhibitors of L-glutamine synthetase, which explains their toxic effect on cells. These derivatives are  used in medical practice for treating inflammation, tuberculosis, and oncological diseases. Bacteria of the Salmonella, Pseudomonas, and Acinetobacter genera are resistant to the toxic effect of MSX and MSO due to the activity of L-methionine sulfoximine acetyltransferases (MSX-NAT). In this work, MSX-NAT from various Enterobacter species from the ESKAPE group of pathogens was analyzed. An  analysis of multiple enzyme alignments revealed a high percentage of their sequence identity, despite the diversity of their polypeptide chain lengths. In addition, unique insertions in the N-terminal region of the proteins were found, the functions of which remain to be clarified.

Three-dimensional cellular models are known to be optimal for studying the response of tissues to external factors due to their ability to accurately replicate the physiological state of cell populations. The present study investigates the metabolic activity and morphological properties of three-dimensional cellular models (spheroids) obtained from human embryo lung fibroblasts FLEH-104 and human fibroblasts hTERT. Cellular spheroids were obtained by means of the low-adhesive surface method using the following cell concentrations: 5, 8, 10, 15, 30, 60 thousand cells/spheroid. The metabolic activity of the as-obtained spheroids was assessed using an MTT-test. The study revealed the dependence of the studied parameters of spheroids on the type of cell lines from which they were obtained, as well as on the initial concentration of cells.

A set of preclinical trials was conducted to study the biomedical properties of personalized model implants based on aluminum oxide in the reconstruction of facial skeletal defects and to substantiate the advantages of their use. The study involved cell cultures and laboratory animals, including at least 30 small-sized laboratory animals (mice or rats) and at least 20 medium-sized laboratory animals (rabbits). The advantages of model implants based on aluminum oxide and titanium aluminum for facial skeletal reconstruction are demonstrated. On their basis, the relevance of integrating the discussed approach into conventional surgical treatment for the majority of patients requiring reconstruction is substantiated.

Alterations in neuraminidase activity can significantly affect neuronal processes. In our previous work, we demonstrated the formation of new synapses as a result of neuraminidase blockage. In the present study, we analyzed the effect of reduced endogenous neuraminidase activity on the synaptic efficacy of newly formed hippocampal synapses. Preincubation of slices with the N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) specific inhibitor resulted in a significant increase in the amplitude of synaptic responses, accompanied by reduced variability and a leftward shift of the input–output curves, suggesting an enhancement of excitatory connectivity within the CA3-to-CA1 hippocampal network.

This article proposes a method for measuring the mass concentrations of bile acids in human blood serum. Monitoring changes in the bile acid content is of great importance for the prevention, diagnosis, and treatment of various diseases. Selective determination of bile acids is a particularly difficult task due to their structural similarities, which complicates their chromatographic separation. Chromatographic separation parameters were selected for eight bile acids. The determination was performed using an Ultimate 3000 liquid chromatograph with a Q-Exactive mass-selective detector with electrospray ionization. The developed technique allows selective determination of eight compounds in a single analysis in a linear concentration range of 10–3000 ng/mL. In future studies, the method will be validated for other parameters.

Atherosclerosis is an inflammatory disease characterized by the accumulation of low-density lipoproteins in the vascular wall and the related immune activation, leading to plaque formation and increased cardiovascular risk. Omega-3 polyunsaturated fatty acids (Eicosapentaenoic and Docosahexaenoic) exhibit anti-inflammatory properties and reduce cardiovascular risk, with the omega-3 index serving as a marker for therapeutic efficacy, including statin response. In this study, a glass fiber carrier for fatty acid analysis in dried blood spots (DBS) was tested. A high correlation was observed between fatty acid levels in whole blood and DBS samples (R²=0.98), outperforming the commonly used cellulose cards. A 1% butyl hydroxytoluene solution applied to the card surface provided omega-3 stability at 84.72% over three weeks of storage. A linear relationship was also found between omega-3 levels in whole blood and erythrocytes (R²≈0.86), supporting the use of conversion models between blood fractions. These findings demonstrate the potential of fiberglass media as a reliable and practical tool for fatty acid profiling in clinical and epidemiological settings.

Peripheral neuropathy is one of the most common adverse effects of chemotherapeutic drugs, including taxanes. Paclitaxel is a cytostatic antitumor drug whose mechanism of action is associated with the stabilization of microtubule polymerization, causing mitosis arrest followed by apoptotic cell death. The need to develop new approaches to preventing and alleviating drug-induced peripheral neuropathy makes the study of its modeling features in laboratory animal particularly relevant. This work analyzes modern approaches to the modeling of paclitaxel-induced neuropathy and identifies factors influencing the severity of pain sensitivity in animals. A review of experimental articles retrieved from the PubMed and Google Scholar databases showed that, at present, repeated intraperitoneal injections of the cytostatic at doses from 2 to 8 mg/kg, simulating chemotherapy in humans, are most often used to model paclitaxel-induced neuropathy. When assessing sex and age differences in the manifestation of symptoms of paclitaxel-induced neuropathy, they were found to be more pronounced in mice compared to rats, being more pronounced in young animals. Thus, when modeling paclitaxel-induced neuropathy in rats and mice, it is necessary to take into account the species, strain, sex and age of animals, the dose and dosing schedule of the cytostatic. Prevention of axonal degeneration caused by chemotherapy may be a new promising direction of research for drug development.

In this work, the effect of chronic intranasal administration of S100A9 proinflammatory protein oligomers, inducing the inflammatory-amyloid cascade, in 24-month-old C57BL/6J mice on the formation and preservation of long-term spatial memory, Th gene expression, as well as dopamine content and metabolism in the hippocampus, frontal cortex, and cerebellum was studied. Compared to the control, experimental animals showed an impairment of the long-term memory on days 3 and 4 of training and testing session in a Morris water maze. Th expression increased significantly in the cerebellum, while dopamine levels decreased significantly in the hippocampus. Thus, chronic intranasal administration of S100A9 oligomers to old animals contributes to the formation of pathological symptoms similar to Alzheimer's disease, thus showing potential as a model of this disease.

Radiobiological effects of the therapeutic beam of carbon ions were studied using a U-70 acceleration complex in mice subjected to total irradiation. Following 30-day survival, a micronucleus test was conducted. The values of relative biological effectiveness (RBE) were determined depending on the dose, linear energy transfer (LET) of carbon ions, and the method of damage registration.

The comet assay method is used to assess DNA damage at the level of individual cells under the action of various factors, such as carcinogens, radiation and oxidative stress. In this study, we set out to evaluate the protective properties of polypore fungus extracts when combined with etoposide, an antitumor drug. The study was conducted using D. melanogaster as a model object. Larvae of the Canton-S laboratory strain were cultured on substrates with polypore fungus extracts (F. pinicola, F. fomentarius, and G. applanatum), both separately (a medium concentration of 0.5%) and in combination with etoposide (0.04%). The extracts of F. pinicola and F. fomentarius did not exhibit protective properties by enhancing the effect of the drug. Conversely, G. applanatum extract exhibited protective properties against DNA damage. The data obtained are promising for the development of new approaches to reducing the side effects of chemotherapy and increasing its effectiveness. 

DNA damage at the level of individual cells is assessed using the method of comet assay. This method allows detection of DNA damage caused by various factors, such as carcinogens, radiation and oxidative stress. In this study, we evaluated the genetic activity of ethanol extracts of four representatives of the Salvia genus using D. melanogaster as a model object. Larvae of the Canton-S laboratory strain were cultured on substrates with the addition of sage extracts (S. stepposa Des-Shost., S. verticillata L., S. tesquicola Klokov and Pobed., S. glutinosa L) under their concentration in the medium of 0.1% and 1%. According to the results obtained, all the studied sage species are not characterized by genotoxicity at a concentration of 0.1%. Under this concentration, S. glutinosa demonstrates antigenotoxic properties, reducing the level of DNA fragmentation relative to the control. When increasing the concentration of the extract in the nutrient substrate to 1%, two representatives of the Salvia genus – S. stepposa and S. verticillate – become to manifest genotoxic properties. Thus, the established concentrations of plant extracts of Salvia species are promising for further study in order to identify effective biological properties.

Accumulation of beta-amyloid peptide (Aß) in the brain followed by the formation of fibrils is a key factor in the progression of Alzheimer's disease (AD). One therapeutic strategy for AD consists in inhibition of fibrillation in its early stages. Today, a large body of research data has been accumulated indicating the ability of nitrogen-containing heterocycles with various substituents to directly bind to Aβ and inhibit its oligomerization. In this work, we consider a new representative of this class of substances – a pyrido-1,3,5-triazine derivative (AAD82) – and construct models of ADD82 complexes with monomeric and protofibrillar forms of Aβ. The correlation of the set of amino acid residues involved in the formation of such a complex, as well as the total energy of its formation, are analyzed.

An experiment on broiler chickens of the Smena-9 cross was conducted to study the effect of hydroxyzine, an anxiolytic, and its complex with ascorbic acid on the leukocyte profile under technological stress, namely an increase in stocking density. An increase in this indicator by 1.5 times in chickens during the period of intensive growth was found to trigger an extreme stress reaction, which is accompanied by changes in the blood system. The quantitative content of leukocytes and the percentage of five leukocyte subpopulations were determined. To assess stress-induced changes in morphological parameters, internal organs were weighed. An increase in stocking density led to changes in white blood cell parameters and an increase in the relative mass of the heart, liver, and kidneys. A trend towards a decrease in relative leukocytosis was revealed when using hydroxyzine both separately and together with ascorbic acid. The combined use of the studied preparations slightly shifts the indices (lymphocyte, leukocyte shift, immunoreactivity, condition index) to the values of the control group. The use of hydroxyzine and vitamin C reduces the relative weight of the heart, lungs, and liver. The conclusion is made about the positive effect of the combined use of the studied preparations on adaptation mechanisms, by mobilizing resistant mechanisms and influencing the functional activity of vegetative organs.

Stress during gestation has a complex impact on the maternal organism and fetal development, leading to long-term changes in the neurophysiology and metabolism of offspring. The aim of this study was to evaluate the adaptogenic potential of lithium ascorbate in correcting stress responses in pregnant sows. The results demonstrate a pronounced modulatory effect of the studied compound on the hypothalamic- pituitary-adrenal (HPA) axis. The data obtained indicate the potential of lithium ascorbate for the prevention of stress-associated reproductive dysfunctions, thus suggesting new possibilities for managing stress reactivity during gestation.

The efficacy of Strongylocentrotus droebachiensis gonad lyophilisate in combined poisoning with carbendazim and X-ray irradiation was assessed in rat biomodels. Two-week intragastric administration of  the lyophilisate was shown to partially compensate for the changes caused by adverse factors, as the same time as exhibiting antioxidant, hemopoetic, and anabolic aciton.

The main objective was to evaluate the biological effects of color-grain varieties of soft spring wheat of  Tatar selection (Nadira – purple-grain, Khazine – yellow-grain) on living organisms using in vitro and in vivo models, including Drosophila melanogaster. The experiments demonstrated that addition of Nadir and Hazine extracts to the substrate for Drosophila larvae significantly increased viability. Thus, when Nadir extract was added at a concentration of 10%, the mean survival rates of females and males were, respectively, 60.5% and 59.5% compared to 40.25% and 39% in the control (p<0.0001). Similarly, when applying 10% Hazine extract, the levels of 55% and 55.75%, respectively, were recorded. DNA-comet assay revealed a 20–25% reduction in oxidative DNA damage with the extracts applied, which correlated with the high content of anthocyanins (Nadira) and carotenoids (Hazineh). PCR data confirmed a decrease in the expression of pro-inflammatory genes (Drosocin, Defensin) in the grain supplemented groups: Drosocin levels decreased from 2.36 to 0.13 (Hazine 5%), Defensin from 2.29 to 0.28 (p<0.05). The Drosophila fecundity was increased by 18–27% using 5% concentrations, and pupal stage mortality was reduced by 30–45% (p<0.01). The results obtained are consistent with the antioxidant and anti-inflammatory properties of bioflavonoids, which are known to reduce the risk of chronic diseases. The study confirms the potential of using colored-grain wheat in the production of functional foods that meet the requirements of the Doctrine of Food Security of the Russian Federation. The development of varieties with increased content of anthocyanins and carotenoids, as well as optimization of processing technologies (e.g., the use of starter to preserve pigments) will extend the range of healthy products such as bread, pasta and cereals, contributing to the health of the population.

Depression and anxiety disorders are among the most common psychiatric problems worldwide. The most important factor leading to the development of psychiatric disorders is chronic stress. TRPV1 channels in the central nervous system are known to be involved in neuronal plasticity and may be one of the links in the development of anxiety and depressive states. In our study, we used a selective blocker of this channel – APHC3, whose administration resulted in a reduction of anxiety and fear in animals in a model of  acute stress. We have identified possible pathways for the development of psychiatric disorders when the body is exposed to chronic stress.

A comparative study of the effects of α-synuclein species (monomers, oligomers or fibrils alone or in combination) administered intranasally for 14 days on passive avoidance in adult (3–7 months) and middle-aged (10–13 months) male C57BL/6 mice was conducted. Middle-aged mice treated with a solution of α-synuclein fibrils and oligomers were found to have a reduced latency to entry in the dark compartment during acquisition phase compared to controls (р<0.05). None of the experimental groups showed any impairment in long-term memory 24 h after training. The data obtained can be used in modeling human neurodegenerative diseases in animals.

Ischemic stroke remains one of the main causes of disability, which requires the search for improved methods of its prevention. In this study, the effectiveness of a hyperoxic oxygen–helium mixture in preventing brain damage during ischemia in Sprague Dawley rats was studied. The blood gas composition, the concentration of 2,3-diphosphoglycerate in erythrocytes, and functional indices were assessed. The results showed that oxygen–helium mixtures exhibit a pronounced protective effect in ischemic stroke, improving tissue oxygenation and reducing neurological deficit.

In this work, we set out to develop a psychophysiological facility for studying neurophysiological mechanisms of social interactions on different activity models of subjects in dyads. The models of activity were sensorimotor training “Columns” as part of a hardware and software complex “BOS-Kinesis” (LTD “Neurotech”, Taganrog, Russia) and the test “Establishment of Laws”, developed and computerized based on B.L. Pokrovsky’s test. Both test tasks are first presented to pairs of subjects for individual performance on single computer monitors separated by partitions. Then the barriers are removed, and the same tasks (sensorimotor training and cognitive test) are proposed to be performed by the participants in a competition setting. Both tasks have also been modified to enable their performance in the context of cooperation between the two partners. The facility is equipped with systems for synchronous recording of EEG and ECG from both subjects in the resting state and during all stages of examination with simultaneous audio and video recording of their activities and possible communications. The developed facility can be used to study the dynamics of performance indicators and neurophysiological characteristics in humans in different social conditions of activity both in individual subjects and their related changes between interacting partners.