Sirtuin 1 (SIRT1) is a class III histone deacetylase that plays a key role in resolving inflammation through known epigenetic mechanisms involving histone and nuclear factor κB (NF-κB) deacetylation. Deacetylation reduces the transcriptional activity of NF-κB and the associated production of pro-inflammatory cytokines such as interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). In the present study, we show for the first time that biomodeling of acute lung inflammation by a single injection of lipopolysaccharide (LPS) induces synchronous oscillations of mRNA levels of cytokines IL-1β, TNF-α, IL-6 and SIRT1 deacetylase in the lungs, the maximum amplitudes of cytokine mRNA oscillations are observed between 1.5 and 5 hours, whereas high levels of SIRT1 mRNA are observed up to 24 hours, when cytokine mRNA oscillations have already faded, which is consistent with the hypothesis about the role of SIRT1 as a factor acting in the phase of inflammation resolution. The study shows that the mechanism of anti-inflammatory action of inhaled hexapeptide Leutragin, a δ-opioid receptor agonist, is related to its ability to increase SIRT1 mRNA expression and decrease the amplitudes of IL-1β, TNF-α, and IL-6 mRNA oscillations in the lungs, which generally leads to the resolution of inflammation in the conditions of biomodeling of acute lung inflammation.

The utility of animal models in preclinical research depends on the completeness of our knowledge about these models. Nonhuman primates are the closest animal model to humans, available for preclinical evaluation of biotechnological products. The lack of immunogenetic characteristics of the primates used in a particular study significantly limits the possibilities of analyzing the results obtained. The availability of information about the haplotype of the major histocompatibility complex (MHC) increases the overall significance of the model. Genotyping of primates at the MHC locus by DNA analysis is excluded, since the representation of individual MHC proteins depends on the level of their expression in immune cells, rather than on their presence in the genome. Therefore, the genotyping of primates at the MHC locus is  carried out by analyzing mRNA encoding allelic variants of proteins. This work presents the results of genotyping of a sample of rhesus macaques from the collection of the Kurchatov Complex of Medical Primatology by a next-generation sequencing technology using an IonProton sequencer.

Toxic damage to various tissues of the body is accompanied by dystrophic and necrotic processes. The nervous system is most susceptible to the influence of exogenous substances both of a chemical and biological nature. Dystrophy is a complex pathological process, which is based on a violation of cell nutrition, leading to age-related and structural changes, as well as neurodegeneration. In toxic lesions, cell death can occur through either necrosis or apoptosis.

The pathogenic microorganism Staphylococcus aureus, one of the representatives of the staphylococcus family, is capable of developing resistance to antibiotics and antiseptics. The largest ribosomal protein, S1, from S. aureus contains four structural S1 domains, and short peptides synthesized based on its sequence have amyloidogenic and antimicrobial properties (antimicrobial peptides). In this work, in silico analysis of all available ribosomal protein S1 sequences from various S. aureus strains allowed us to identify residues that are characteristic of specific strains. Based on data from the I-Mutant service, changes in the stability of ribosomal protein S1 from various S. aureus strains were predicted. The results obtained will be used in the future for targeted mutations in the design of new antimicrobial peptides based on ribosomal protein S1.

We present the results of a histological study into the cardiotoxicity of conjugates of daunorubicin with dehydrocostus lactone and epoxyisoalantolactone in mature male mice of the C57BL/6 line. The effect of conjugates on the morphology of cardiomyocytes and the structure of the left ventricular myocardium in mice was studied.

Bacterial N-terminal acetyltransferases (NATs) are involved in the biosynthesis/degradation of antibiotics. The RimL enzyme from E. coli provides it with resistance to the antibiotic microcin C. To date, the NATs of pathogenic bacteria have been well studied, but there is no data on the NATs of thermophilic bacteria. The purpose of the work is to study the physicochemical properties and specificity of a new NAT — RimL from Thermus thermophilus. We cloned the RimL ORF (TTHA1799) and developed a method for purifying the enzyme. The stability of RimL to pH, high temperatures and denaturing agents was studied using the protein intrinsic fluorescence method. We have obtained a thermophilic enzyme that can be used in biotechnology for the acetylation of proteins and peptides under non-standard conditions.

The creation of a validated model of the “chemical brain” in laboratory animals is an urgent task, the solution of which will optimize the search for new drugs for the prevention and pharmacological correction of delayed effects of chemotherapy on the central nervous system. The aim of the work has been to assess the effect of doxorubicin after systemic course administration on behavioral reactions and the microscopic view of the cerebral cortex and hippocampus in rats.

Doxorubicin was administered intraperitoneally to male rats at doses of 5 and 6 mg/kg, once a week, for 28 days. The behavioral reactions of the animals were assessed, and pathomorphological studies of the cerebral cortex and hippocampus were carried out.

Doxorubicin at doses of 5 and 6 mg/kg causes inhibition of motor activity in the “Open Field” test, impairment of non-spatial and spatial memory in the “New Object Recognition” and “Y-Maze” tests, respectively. Doxorubicin at these doses increases the severity of vascular congestion and perivascular edema in the cerebral cortex and hippocampus.

Doxorubicin at doses of 5 and 6 mg/kg causes impairment of cognitive functions in rats in tests assessing non-spatial and spatial memory, as well as microcirculation disorders in the cerebral cortex and hippocampus of rats.

The acute toxicity and the ability of cholinoreceptor agonists to induce atypical motor hyperactivity in zoohydrobionts Daphnia magna Straus, equivalent to a significant seizure state in warm-blooded animals, were evaluated. Determination of this test function may be useful in screening assessment of pharmacological activity of cholinergic substances.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic chemotherapy. In a large number of patients, this complication is highly persistent to treatment. The present review is focused on current rodent CIPN models using antineoplastic agents of different groups.

In this work, we study the effect of Asparagus racemosus (EAR) and Ajuga turkestanica (EAT) dry extracts at a dose of 100 mg/kg in comparison with a Rhaponticum carthamoides extract (ERC) on the effectiveness of an aerobic–anaerobic training regimen in female mice in a triple-weight loaded exhaustive swim test with a 10% load of body weight, as well as on the level of malondialdehyde and catalase activity in blood hemolysate, cardiac and skeletal striated muscle tissue, and liver homogenate. The results obtained indicate a reduced severity of lipid peroxidation under the influence of dry EAR and EAT extracts, thus pointing to the antioxidant activity of the extracts. In the conducted triple-weight loaded exhaustive swim test, a statistically significant increase in the duration of swimming No. 3 and the test index was noted in both groups compared to the control. Therefore, it can be concluded that the studied extracts have a positive effect on the first-phase recovery processes.

Quality assurance plays a key role in preclinical research, where every detail must be strictly controlled and verified. Standard operating procedures are essential part of any quality assurance system, defining precisely the steps and methods of implementing certain tasks or processes in a laboratory. In this article, the main components of a quality assurance system are discussed using the example of studying the pharmacological safety of a malonic acid derivative.

The article presents the results of experimental studies into the efficacy of dual combinations of conventional drugs for the basic treatment of chronic heart failure with empagliflozin when modeling the pathology in laboratory outbred rats. As part of the study, survival, physical tolerance, and echocardiographic parameters were assessed. The most effective combination was found to be the therapy by empagliflozin with fosinopril. In this case, the six-month survival rate achieved 90%; a greater tolerance to physical activity was observed (50% increase in relation to animals in the pathology group without treatment); shortening and  ejection fractions increased by 25%.

The dynamics of basic parameters of metabolism and lipid peroxidation in the blood serum of rats was studied during the formation of a state of hyperthermia (exposure to air at a temperature of +40 °C for 60 min). It was found that the albumin/globulin ratio, uric acid, cholesterol, triglycerides, blood electrolytes, as well as the activity of the enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, superoxide dismutase, glutathione peroxidase under short-term heat exposure did not have statistically significant differences from the values in the state of normothermia. The level of lipid hydroperoxides and reduced glutathione changes significantly already during the mobilization phase of thermoregulatory mechanisms. The dynamics of these indicators are stable, which allows these indicators to be correlated with hyperthermia itself.

The article presents the results of testing a heart failure model in laboratory animals by single administration of amyloidogen. White outbred mice were used as biomodels, which were divided into intact and experimental groups. Animals from the experimental group were once injected with amyloidogen containing mouse myocardial homogenate to reproduce a pronounced cardiopathic effect. Structural and functional changes of the myocardium were monitored using echocardiography. According to the results obtained, animals in the experimental group demonstrated a remodeling of the heart similar to restrictive cardiomyopathy and a myocardial disfunction of both ventricles, indicating the formation of heart failure.

Currently, biologically active substances of natural origin are widely used as preventative agents. The search and development of new drugs for the prevention and correction of nonspecific disorders of the body’s resistance to adverse effects in environment continues. A preclinic assessment of the effectiveness of polyprenols from Siberian fir Abies sibirica was carried out when used prophylactically for two weeks. It has been shown that the effect of polyprenols is manifested by antioxidant, anabolic activity and stimulation of hematopoiesis in an experimental model of combined poisoning with carbendazim and X-ray irradiation.

Ammonia as the end product of protein catabolism has a depressing effect on neurons. Ammonia neutralization in mammals occurs in the ornithine cycle, the activity of which is regulated mainly at the level of synthesis of N-Carbamoyl phosphate. The Krebs cycle is coupled with the ornithine cycle through a common substrate—arginine succinate. Therefore, the effects of ammonia neutralization and the processes of amino acid and energy metabolism are largely interrelated. This study is aimed at evaluating the  efficacy of an N-carbamoyl glutamate additive in terms of optimizing metabolic processes and improving ammonia neutralization in suckling piglets. The experiment was conducted on two groups of piglets (n=15) formed at the age of 24 hours. Piglets in the experimental group were fed with an aqueous solution of the drug at  a dose of 10 mg/kg of body weight once daily. The duration of feeding the supplement was 30 days; the average daily gain in body weight was determined at weaning at the age of 30 days. An analysis of the blood biochemical composition was carried out on the 30th day from the onset of the experiment. At the end of feeding the supplement in the experimental group, a decrease in the content of ammonia (p<0.05) and urea in blood plasma, an increase in the concentration of arginine (p<0.05) and triacylglycerols (p<0.05) in comparison with the control group was revealed. The N-carbamoyl glutamate additive under study stimulates the endogenous production of the arginine essential amino acid, neutralizes ammonia formed in metabolic processes, and optimizes the amount of metabolic energy spent on binding ammonia in the urea cycle.

Benign pigmented skin lesions, including congenital giant pigmented nevi (CGPN), are pathological formations located in various skin layers and consisting of melanocyte clusters. CGPN represent a serious psychological and medical problem associated with extensive unaesthetic changes in the patient’s skin appearance. These lesions are currently treated by various methods, including laser radiation. However, such methods often render ineffective and lead to unsatisfactory clinical and aesthetic results, with the incidence of complications in the form of scarring and recurrence sometimes reaching 41%. Therefore, the problem of effective and appropriate treatment of this pathology is relevant, deserving further research. In this work, we conduct an experimental biomedical study into the effect of blue laser radiation with a wavelength (λ) of 450 nm on the tissues of laboratory animals in order to determine its prospects in the treatment of pigmented nevi, including CGPN. Blue laser radiation (λ — 450 nm) was generated by an Lasermed 10-03 device (Russian Engineering Club, LLC, Tula, Russia). An experimental biomedical in vitro research was performed on chilled samples of the liver and muscles of mini-pigs and in vivo on the pigmented skin of live laboratory rats. The dynamics of the regenerative wound process in the exposure areas was studied at different periods, i.e., immediately after exposure and following up to 90 days. A morphometric assessment of the exposure areas was carried out in terms of penetration depth and coagulation changes. The results obtained allowed determination of optimal parameters of 450 nm blue laser radiation for a precision removal of various pigmented skin formations. Laser radiation with a wavelength of 450 nm is a promising treatment approach for pigmented skin lesions, including CGPN.

Experiments on 39 male Wistar rats were performed. A metal-organic coordination polymer modified with iron oxide and ascorbic acid (composite) was administered intravenously to healthy rats at doses of 25 and 50 mg/kg. The anti/prooxidant activity of the composite was assessed 3 and 24 hours after administration. The composite in both doses was shown to have no significant effect on the homeostasis of prooxidants/antioxidants in the blood serum in healthy animals. In high doses, the composite enhances apoptosis of lymphocytes, which indicates its possible use as a catalyst for free radical processes for further use in biomedicine.

Traumatic brain injury (TBI) is associated with varied and unpredictable consequences, which can be manifested during both acute and long-term periods. Such consequences may lead to the development of neurodegenerative diseases years and even decades after the injury. Given the heterogeneous nature of  TBI in humans, preclinical studies need to be conducted using different test systems. Currently, preference is given to rodents due to their availability and low cost. However, the choice of test systems for research should be based not only on economic and logistical components, but also on their specific physiological characteristics.

The article presents a brief overview of the modern view on the problem of the combined use of drugs with a multidirectional spectrum of action, anticoagulants and hemostatics, in major orthopedics among patients with endoprosthetics of large joints of the lower extremities. Variable prescription regimens of anticoagulant prophylaxis against the background of using hemostatic drugs were analyzed.

Over the past two decades, much evidence has accumulated that confirms the crucial role of alternative splicing in the process of tumorigenesis. A more detailed study of splicing mechanisms revealed that targeting the central process for atypical cells could be a potential new approach in the treatment of malignant neoplasms. Firstly, specific protein isoforms that are formed as a result of alternative splicing and are involved in tumorigenesis can potentially act as a target for the treatment of malignant neoplasms. Second, high rates of cell proliferation presumably make tumor cells highly dependent on a functional spliceosome, creating potential hypersensitivity to global splicing modulation. The study of the role of alternative splicing in tumorigenesis and the search for therapeutic targets contributed not only to the development of  a more promising direction in oncology, but also to the search for new drugs that have a targeted effect on the development of malignant neoplasms.