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The naked mole-rat (NMR) is a unique long-lived rodent with low cancer incidence. Understanding the molecular mechanisms that NMR evolved to control aging and tumorigenesis is important for biomedicine. It is commonly accepted that the immune system has essential functions in the tumor growth control in animals. In-depth study of the NMR immune system has recently begun, thus peculiarities of antitumor response in these animals remain undiscovered. However, it was shown that myelopoiesis predominates in NMR, therefore it can be assumed that the innate immune cells in the naked mole rat contribute to the successful control of the cancer incidence and tumor growth. This brief provides an overview of ongoing research into the properties of naked mole rat macrophages. Recent study shown that naked mole rat peritoneal macrophages are capable of acquiring an inflammatory phenotype (M1) but polarization into an anti-inflammatory phenotype (M2) under standard stimulus is limited. A more in-depth study using transcriptome sequencing and immunometabolic profiling in novel in vitro model of naked mole rat bone marrow macrophages suggested by our group revealed non-canonical features of M1 as well as M2 phenotypes of naked mole rat macrophages, which can be associated with the evolutionary adaptation of the species. Continued study of the different polarization conditions of naked mole rat macrophages is important to determine unique adaptations in NMR antitumor immunity.

The aim of this study was to assess the production of reactive nitrogen species in the hearts of rats subjected to surgical trauma simulated against the background of post-traumatic stress disorder (PTSD). Materials and methods.The study was conducted on 42 white Wistar rats weighing 210-230 g, then divided into 6 groups: Group 1 consisted of intact animals, Group 2 included animals exposed to the induction of the PTSD model through single-prolonged stress (SPS), Group 3 – rats subjected to a sham operation, Group 4 – animals undergoing laparotomy, Group 5 – rats undergoing a sham surgical operation following SPS, and Group 6 – animals undergoing laparotomy under modeled SPS. NO synthase activity in the heart homogenate was determined spectrophotometrically. Results. The formation of peroxynitrite was assessed by the content of peroxynitrite of alkaline and alkaline-earth metals. SPS exposure significantly increases the production of reactive nitrogen species in the hearts of rats, in particular, it enhances NO synthase activity by activating the inducible isoform and reduces the activity of constitutive NO synthases, which is accompanied by the growth in the concentration of peroxynitrites. On the 7th day after laparotomy against the background of the experimental PTSD model, the indicators of nitrosative stress in the hearts of rats (total and inducible NO synthase activity and peroxynitrite concentration) significantly exceeded their values in the groups subjected to a single laparotomy and to a sham operation against the background of simulated SPS.

The aim of the study was to evaluate the effect of curcumin on the ratio of constitutive and inducible NOS isoforms in the cerebral cortex of rats under a round-the-clock lighting (RCL) with a high fructose and fat diet. The experiments were performed on 21 white Wistar rats weighing 235±20 g, divided into 3 groups. Animals in the first group (control) received a standard diet (energy value 2720 kcal/kg) and were exposed to an equal alternation of light and darkness. The rats of the second and third groups were kept in RCL conditions against the background of the administration of a high-calorie carbohydrate-lipid diet (HCCLD, 4477 kcal/kg). In addition, animals of the third group received curcumin daily through a gavage, intragastrically, at a dose of 200 mg/kg. The activity of total NOS and its constitutive isoforms (cNOS) in the cerebral homogenate was measured, inducible isoenzyme (iNOS) activity and cNOS coupling index were calculated. Curcumin administration significantly reduced the total and inducible activity of NOS in the cerebral homogenate– by 34 and 38%, respectively, compared with the values of the second group. At the same time, cNOS activity (2.3-fold) and its coupling index (3.8-fold) increased significantly compared with the data of the second group. It is concluded that the use of curcumin in metabolic disorders associated with pathogenic factors of the “Western lifestyle” – light disorders and the use of HCCLD restores the normal ratio of constitutive and inducible NOS isoforms, cNOS coupling in the rat cerebral hemispheres, which prevents the development of oxidative-nitrosative stress.

Introduction. Helicobacter pylori (Hp) is a class I biological carcinogen and the third leading cause of cancer death in the world, according to the World Health Organization. Hp infection represents a global public health problem in the 4.4 billion people living with Hp worldwide. The pathogenesis of helicobacteriosis is multifaceted: disorders in the nitric oxide (NO) system are involved in the development of the disease, along with other mechanisms. These aspects of the pathogenesis of helicobacteriosis are not well understood. In particular, such parts of the general problem as the significance of changes in the level of NO, its metabolites in the development of inflammatory and erosive-ulcer diseases of the gastroduodenal zone caused by different genotypes of Hp are not solved. After HP eradication, the content of NO synthase in the gastric mucosa decreases. However, the expression of the enzyme remains high in areas of intestinal metaplasia, which is considered the source of continued production of NO synthase even after Hp eradication. Aim. To investigate the level of nitrates/nitrites in the blood in patients infected with various genotypes of Hp. Materials and methods. 48 patients with inflammatory and erosive-ulcer diseases of the stomach and CPD infected with Hp were examined. R&D Systems kits were used to determine the level of nitrates/nitrites in the blood. For the diagnosis of helicobacteriosis, a classic respiratory test was used, as well as a polymerase chain reaction. CagA, VacA, BabA, IceA genotyping Hp was performed. Depending on gene detection, Hp strains were divided into 4 serotypes: type I (CagA+, VacA+)/Type Ia (CagA+, VacA-), type Ib (CagA-, VacA+), type II (Vac A-, CagA-). Discussion. Нр harboured the CagA gene in 34 patients (70.8% of cases), VacA gene in 40 patients (83.3%), BabA gene in 6 patients (12.5%), and IceA gene in 8 patients (16.7%). The distribution by Нр serotype showed that serotype I was found in 28 patients (58.3%), serotype Ia in 6 patients (12.5%), serotype Ib in 12 patients (25.0%), and serotype II in 2 patients (4.2%). In general, all surveyed patients had blood levels of nitrates/nitrites that were significantly increased to 54.7±2.4 μmol/L (compared to the levels of healthy individuals, p

Nitric oxide as a therapeutic approach to the treatment of cardiovascular diseases attracted the attention of researchers at the end of the 19th century. As a vasodilator, nitric oxide may be a unique therapeutic agent for the treatment of hypertension and, as a result, renal failure and left ventricular hypertrophy.The aim of the article is to analyze the literature data on possible ways of modulating the activity of various nitric oxide synthases as an approach to the treatment of endothelial dysfunction.Materials and methods. When searching for materials for writing a review article, such abstract databases as PubMed, Google Scholar, e-Library, etc., were used. The search was carried out on the publications for the period from 1990 to 2021. The following words and phrases were chosen as parameters for the literature selection: nitric oxide; NO synthase; endothelial dysfunction; NO synthase activator; NO synthase inhibitor.The following words and phrases were chosen as parameters for the literature selection:Results. The article presents the history of the nitric oxide discovery and its biological role, the process of its biosynthesis, as well as the isoforms of its synthesizing enzymes (NOS): neuronal – nNOS, endothelial – eNOS and inducible iNOS, and their role in normal and pathological physiology. The process of NOS uncoupling (its molecular mechanisms) has been considered as the basis of endothelial dysfunction.The examples of the pharmacological correction (BH4, arginase inhibitors, statins, resveratrol) are presented. In addition, NO synthase activators (calcium dobesilate, cavNOxin, and some NOS transcription activators), as well as non-selective (L-NMMA, 1-NNA, L-NAME, ADMA, 546C88, VAS203) and selective (L-NIO, 7-nitroindazole, aminoguanidine, L-NIL, GW273629, GW274150, cavtratin) inhibitors of nitric oxide synthasehave been described.Conclusion. Nitric oxide synthases continue to be promising targets for the development of agents that modulate their activity to correct various pathologies. As a therapeutic approach, modulation of the nitric oxide synthase activity can be implemented to treat endothelial dysfunction, which is the cause for complications of many diseases.

One of the important medical and social present-day problems is atrial fibrillation (AF) which prevalence in the adult population is 2 % for persons under 65 and 9 % for those over 65 years of age and it is a common cause of ischemic stroke. The embolic complications incidence is 2.1 % per year in patients with paroxysmal AF, and 3.0 % per year in patients with persistent AF. The aim of the study is to analyze the modern literary sources related to the role of gene polymorphisms regulating some neurohumoral systems in group of patients with atrial fibrillation. A combination of certain genes polymorphisms can contribute to AF risk. Especially important are gene studies of the renin-angiotensin-aldosterone system (RAAS) role in the pathogenesis of AF which are currently being studied with a particular intensity. Recent data show that activation of RAAS plays an important role in the development and recurrence of AF. These studies are of great practical interest as the associative effect of angiotensin converting enzyme (ACE) inhibitors in the prevention of AF has been identified. AGT gene encodes a plasma protein known as angiotensinogen. This protein is expressed in the liver and is cleaved by the enzymatic renin action in response to lower blood pressure. The resulting product, angiotensin I, is then cleaved by ACE to the physiologically active enzyme angiotensin II. Defects in this gene may also be associated with non-hereditary AF. More than 16 spot mutations in the AGT gene were discovered, most of which resulted in amino acid substitutions. Conclusions. The analysis of the literature allows to conclude that, first, genetic polymorphisms may influence both the severity of pathological changes in the body and the efficacy of pharmacotherapy, and second, the study of RAAS gene polymorphisms may allow early detection of persons with increased risk of persistent AF recurrence and its prevention.

The purpose of this study was the assessment of asymmetric dimethylarginine (ADMA) and its links with carbohydrate and lipid metabolism parameters in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus following determination of asymmetric dimethylarginine and NO synthase plasma levels. Materials and methods. The study included examination of 73 patients with acute myocardial infarction and type 2 diabetes mellitus, 57 patients with AMI without type 2 diabetes and 20 conditionally healthy individuals. The content of ADMA and NO synthase was measured by using an enzyme-linked immunosorbent assay kit (ADMA Xpress ELISA kit;Immundiagnostik,Austria) and Bender MedSystem (Austria), respectively. The parameters of carbohydrate and lipid metabolism were determined by a standard biochemical method. Results. A significant 2.64 times increased level of ADMA (1.24 ± 0.04 μmol/L) was found in the patients with AMI and type 2 diabetes compared to the practically healthy persons (control group) (0.47 ± 0.05 μmol/L), and 2.53 times increased (P < 0.05) in comparison with the patients without type 2 diabetes. In the presence of type 2 diabetes the 40.1 % (P < 0.05) decrease in NOs level was noted compared to the control group (3.12 ± 0.11ng / ml and 5.21 ± 0.19 ng/ml, respectively) and the 26.1 % (P < 0.05) decrease compared to the patients with AMI without type 2 diabetes. The study provided a possibility to determine a direct correlation between ADMA and total cholesterol (r = 0.47; P < 0.05); LDL cholesterol (r = 0.28; P < 0.05), HDL cholesterol (r = -0.39; P < 0.05), triglycerides (P = 0.35; P < 0.05), glucose (P = 0.46; P < 0.05), insulin = 0.49; P < 0.05), glycosylated hemoglobin (r = 0.39; P < 0.05). Correlation analysis showed an inverse correlation between ADMA and NO synthase levels (r = -0.67; P < 0.05). Conclusions. The association between asymmetric dimethylarginine high levels and pathological changes in the parameters of carbohydrate, lipid metabolism and endothelial dysfunction has been established, which increases ischemia in the vessel wall and adversely affects the course and prognosis of acute myocardial infarction in patients with type 2 diabetes mellitus.