Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The activity of APHC2, a new polypeptide modulator of TRPV1 receptors that was isolated from Heteractis crispa, is studied. It was established that APHC2 possessed analgesic properties, did not disturb normal locomotor activity, and did not change body temperature and hemostasis of experimental animals. These attributes could be of great practical value for designing a new generation of efficacious analgesics. A brief increase of heart rate was observed during studies of the hemodynamic activity. Further investigation of the binding specifics of this polypeptide with TRPV1 receptors could open approaches to discovering other antagonists of these receptors.

© 2018 Elsevier Ltd Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin–receptor interaction, we used 25 derivatives of potent cytokinin N6-benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis. The main in planta assay system was based on Arabidopsis double mutants retaining only one isoform of cytokinin receptors and harboring cytokinin-sensitive reporter gene. Classical cytokinin biotest with Amaranthus seedlings was used as an additional biotest. In parallel, the binding of ligands to individual cytokinin receptors was assessed in the in vitro test system. Quantitative comparison of results of different assays confirmed the partial similarity of ligand-binding properties of receptor isoforms. Substituents at positions 8 and 9 of adenine moiety, elongated linker up to 4 methylene units, and replacement of N6 by sulfur or oxygen have resulted in the suppression of cytokinin activity of the derivative toward all receptors. Introduction of a halogen into position 2 of adenine moiety, on the contrary, often increased the ligand activity, especially toward AHK3. Features both common and distinctive of cytokinin receptors in Arabidopsis and Amaranthus were revealed, highlighting species specificity of the cytokinin perception apparatus. Correlations between the extent to which a compound binds to a receptor in vitro and its ability to activate the same receptor in planta were evaluated for each AHK protein. Interaction patterns between individual receptors and ligands were rationalized by structure analysis and molecular docking in sensory modules of AHK receptors. The best correlation between docking scores and specific binding was observed for AHK3. In addition, receptor-specific ligands have been discovered with unique properties to predominantly activate or block distinct cytokinin receptors. These ligands are promising for practical application and as molecular tools in the study of the cytokinin perception by plant cells.

© 2018 Izdatel'stvo Meditsina. All rights reserved. NMDA receptor modulators are a new class of antidepressants with rapid onset of action and lasting antidepressant effect. These drugs increase BDNF level in CNS and adult hippocampal neurogenesis, which events are in common for both NMDA receptor modulators and classical antidepressants. However, unlike classical antidepressants, drugs of this new group produce no direct influence on the monoaminergic system, but regulate the neuroplasticity in the prefrontal cortex and hippocampus via modulation of the glutamatergic neurotransmission. Clinical tests of ketamine and rapastinel confirmed the rapid onset of action and the continuation of stable antidepressant effect (upon single administration per 7 days) for both usual and treatment-resistant forms of depression.

© Saint Petersburg Pasteur Institute. All rights reserved. The aim of the present systematic literature review is to summarize data on the role of TLRs in maintaining homeostasis of the female genitals, in maintaining the physiological development of pregnancy, provision of anti-infective resistance in pregnant women with intrauterine infection. The review substantiates the importance of TLRs of female genitals as a necessary and determining factor in the reaction to various changes in the environment, and also responsible for changes in metabolic, structural, or energy, in the maintenance of anti-infective resistance and homeostasis. As universal regulators of vital activity of organism TLRs in conjunction with other receptors of innate immunity provide maintaining the general reactivity and anti-infective resistance at the physiological level. In physiologically developing pregnancy in a background of immunosuppression in response to pregnancy TLRs during contact with infectious and non-infectious pathogens stimulate the production of nonspecific adaptive immunity factors (defensins, cathelicidins, histatines, etc.), which together with the non-specific innate factors lysozyme, complement, properdin, etc. support anti-infective resistance of the female genitals at a high level at the beginning of the infectious process. Possible violations of the development of pregnancy may be accompanied by changes in the response of TLRs to infectious and non-infectious factors until hyper-reaction, excessive inflammation or apoptosis, which requires adequate management of pregnancy. Was established the significance of the influence of pathogens of infectious and noninfectious origin in intrauterine infection indirectly through TLRs in the homeostasis of the organism, on the formation of breaches in anti-infective resistance at the organism and community level the identification of new pathophysiological and immunological pathogenetic mechanisms of development of pathological processes. IUI is a penetration of microorganisms into the tissues of fetus and it's infection. The inhibition of the functional activity of TLRs is accompanied by the direct effect of the pathogen on the tissues, and during hyper-reaction of TLRs to pathogens revealed a pronounced inflammatory response in the fetus. The level of expression of TLRs correlates directly with the severity of the process that can be considered as early markers of infection. Depending on the nature of the pathogen an increased expression of one or the other TLRs is observed. Explained the lack of symptoms, the possibility of atypical manifestations, the asymptomatic course of infection.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review article considers the modern notions about glucocorticoid hormones. Particular attention is paid to their molecular mechanisms of action, with emphasis on the importance of studying new compounds of the group of selective modulators of glucocorticoid receptors.

© 2018 Dynasty Publishing House. All rights reserved. The objective: The purpose of the study is to establish the role of infection with herpes simplex viruses type I and II in the pathogenesis of urogenital infection in pregnant women. Patients and methods: 89 patients of I, II trimester gestation, aged 18 to 35 years (average age of 27.5 ± 5.6 years) were examined. The design of the research and the methodology of verification of the UGI pathogens of pregnant women are presented in previously published materials. The establishment of character of pregnancy course (urgent delivery, premature birth, termination of pregnancy and mis-carriage), the presence or absence of infection and/or clinical manifestations of infectious and inflam-matory diseases, as well as evaluating the gene expression of TLR-2, TLR-3, TLR-4, TLR-8 (in relative units - RU) was conducted according to manuals. Results: It is established, that in UGI in pregnant combined viral-bacterial infection is registered. Viral component of UGI pathogens in pregnant women is presented by the association of viruses from the Herpesviridae family - herpes simplex viruses, Cytomega-lovirus, Epstein-Bar virus. Against the background of polyfactorial mechanisms of the pathogenesis of abortion, extra maximum activation of gene expression of TLR (22-23 RU or more) additional external factors, for example, infections can be an aggravating pathogenetic factor of miscarriage. Reduced expression of genes of TLR2, TLR4, TLR3 and TLR8 in the mucous membrane of the cervical canal in UGI of pregnant women in infection with herpes simplex virus due to the oppressive effect of pregnancy on the reaction of TLR, combined with the immunodepressive effect of the virus itself. With the violation of cellular part of immuno-logical reactivity of the body under the influence of adverse endogenous and exogenous factors on the process of pregnancy is activated the infectious process caused by the bacte-rial-viral pathogens association, which is accompanied by hyper reaction and increased reaction from the expression of genes of TLR, determines the pathological development of pregnancy. It is established that in the UGI of pregnant gene expression levels of TLR2-21.2 and above, TLR4-23.0 and above, TLR8 - 26.0 and above (the level of gene expression of TLR8 above 28 is the predictor of the onset of abortion and miscarriage) testify to the acute infectious process with the clinical manifestations of the UGI, and also indicates the possible interruption of pregnancy and miscarriage; levels of gene expression of TLR2 below 21.2, TLR4 below 23.0, TLR8 below 26.0, in-dicated a decrease in the severity of the infectious process and its chronicity, as well as the possibility of direct microbial damage to the tissues of UGT, placenta, and fetus. Conclusion: Verified in preg-nant women in 61% of cases clinical manifestations of the infectious process are necessarily associated with the verification of the association of herpes simplex viruses I and II type - triggers of infectious process deterioration, determining the prognosis and outcome of the development of the UGI in preg-nant.

© 2018, SPb RAACI. The aim of this work was to study features of gene expression TLR2, TLR4, and TLR9 in the course of acute respiratory infection, depending on the time elapsing since the contamination, and dose of infection. The studies of in vivo models of acute respiratory infections caused by Gram-negative Klebsiella pneumoniae showed that, at infection dose of 104 CFU/ml, the TLR4 gene expression levels in epithelium of upper respiratory tract at 1, 3, 10 days were increased 30 times and more, complete elimination of the pathogen was observed at 3 days. At the dose of infection of 107 CFU/ml, persistence of the pathogen in upper respiratory tract was observed within a few days, accompanied by a significant increase in the level of TLR9 expression in epithelium of upper respiratory tract, and TLR4 levels in the lungs 1 day after infection, in parallel to elimination of the pathogen from the lower respiratory tract. Thus, the characteristic features of TLR4 and TLR9 gene expression in the upper respiratory tract may be considered a potential diagnostic and prognostic factors in evaluation of the course of acute respiratory infections caused by Klebsiella pneumoniae.

to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. Subjects and methods. The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. Results. According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. Conclusion. Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

© 2019, SPb RAACI. Inhibitory receptors CTLA-4 and PD-1 (immune checkpoints) play a key role in regulation of immune reactions. They suppress excessive immune response against pathogenic microbes and prevent autoimmune reactions. The immune checkpoints are targets of the modern effective therapy based on human and humanized monoclonal antibodies (ipilimumab and nivolumab, tremelimumab, pembrolizumab, etc). However, despite its high efficiency compared to standard chemotherapy, the therapy based on blocking immune check points is facing several problems, i.e., high therapy cost and severe negative autoimmune-related side effects. Unfortunately, this therapy helps to minority of the patients. Hence, further studies are required to improve its efficiency and safety, as well as to search for selection criteria of the patients who would benefit from the therapy. An appealing approach to reduce negative side effects from immune checkpoint inhibition is application of the blocking antibodies, aiming for ex vivo generation of patients’ activated immune cells for cancer therapy, thus avoiding systemic drug administration. Our aim was to elucidate influence of immune checkpoint blocking antibodies on the expression of CTLA-4 and PD-1 in such an in vitro model. First of all, we have determined quantities of lymphocyte receptors in peripheral blood of healthy volunteers, or cancer patients with disseminated melanoma. Moreover, we defined effect from the addition of antibodies against immune checkpoints on proportions of cells expressing CTLA-4 and PD-1 in the population of phytohemagglutinin-activated lymphocytes. Our study demonstrated that, in presence of antibodies to either of the two checkpoints during in vitro cell activation, the blockade of specific target receptor is accompanied by reduced number of cells positive for another checkpoint. Hence, the antibodies directed against PD-1 or CTLA-4 seem to suppress both negative signal cascades at once, if tested under such experimental conditions. Noteworthy, the response to blocking antibodies for different immune checkpoints varied for different donors. Our data may be used for development of effective combinations of lymphocyte activators and immune check-point inhibitors, for in vitro generation of activated lymphocytes applied for adoptive cancer therapy, as well as for prediction of possible responses to antibodies against CTLA-4 or PD-1, aiming to select the best personalized cancer immunotherapy.

© 2018 Ruslania. All rights reserved. This literature review is devoted to modem notions about molecular mechanism of action of the selective modulators of progesterone receptors. The superfamily of nuclear receptors represents ligand-activated transcription factors and includes receptors for steroid hormones, lipophilic vitamins, sterols, and bile acids. These receptors serve as targets for creating numerous drugs. As a result, a new class of compounds (ligands) appeared exhibiting agonistic/partial agonistic/antagonistic functional activities depending on the context (tissue or gene target). This class of ligands is called selective modulators of nuclear receptors. Initially, mifepristone was developed as the progesterone receptor antagonist, but further it demonstrated the properties of a selective modulator of progesterone receptor and became the ancestor of this group. At present, the development of new selective modulators of progesterone receptor is aimed at obtaining higher selectivity with respect to progesterone receptors and decreasing the anti-androgenic and anti-glucocorticoid properties. Unfortunately, most of the subsequent selective modulators of progesterone receptors exhibited hepatotoxicity, which limited their wide introduction into clinical practice.

© 2018 Russian Academy of Sciences. All rights reserved. The current theoretical and experimental data about the impact of the lipid A structure on interactions of lipopolysaccharide (LPS) with serum lipid-binding protein (LBP) are presented. LBP interacts more efficiently with the LPS lipid A from Rhizobium, Escherichia, and Neisseria spp. than with the LPS lipid from Francisella, Porphyromonas, Helicobacter, Chlamydophila, as well as with the lipid A synthetic analogue-compound E5564. It is shown that the lipid A hydrocarbon chain of 14 carbon atoms is most favorable, while that of 16 carbon atoms is ultimate for interaction of LBP with lipid A. A high content of unusually long chains and branched-chain acyl residues in lipid A will further complicate the interaction of LBP with LPS. The reviewed data provide a deeper insight into the mechanisms of the LPS delivery and cell activation accomplished by serum cationic proteins such as LBP. A direct relation between the efficiency of the LBP interaction with a particular lipid A of LPS and the development of the fulminant acute inflammation is proposed.

THE PURPOSE OF THE STUDY: determination of the optimal parameters of the action of various types of current, which have the most pronounced irritating effect on the receptor apparatus of the tooth pulp. The study involved 102 volunteers aged 19 to 72 years (53 females and 49 males). The study was conducted on 217 teeth: 86 molars, 25 premolars, 19 canines and 98 incisors. 137 (63%) teeth were intact, in 48 (22%) teeth caries were found, in 32 (15%) teeth there was pulpitis or teeth were depulpated. Electroexcitability of the teeth was determined with the help of various types of electric current: an impulse variable, an impulse constant and a sinusoidal variable. The optimal current for carrying out an electroodontodiagnosis proved to be sinusoidal variable current with a frequency of 50 Hz. This current does not cause polarization of tissues, it is easy to dose, it causes a clear, but not painful sensation, gives the smallest spread of the indicators during repeated studies. The obtained results allowed formulating requirements for electroodontodiagnosis devices.

© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved. background. Adrenocortical cancer (ACC) is a rare malignancy of the adrenal cortex. Therapeutic options for advanced ACC are limited. It is necessary to study new and more effective drug combinations and tumor biological targets. the purpose of the study was to determine the expression of somatostatin receptor subtypes 2A and (SSTR 2A and SSTR 5) using immunohistochemical (IHC) analysis of tumor tissue samples in patients with ACC, as well as to study the feasibility of using prolonged analogues of somatostatin in the treatment of advanced ACC. material and methods. The expression of SSTR 2A and SSTR 5 was analyzed using imunohistochemistry of tumor tissue samples from 20 patients with advanced ACC. results. The negative (0) IHC status of SSTR 2A and SSTR 5 was determined in 10 patients (50 %). A different staining intensity of SSTR 2A and SSTR 5 expression was found in tumor cells of 10 patients (50 %). The low SSTR expression was associated with low membrane immunoreactivity and high SSTR expression was associated with moderate and strong immunoreactivity. High level of somatostatin receptor expression was detected in 7 patients (35 %). Conclusion. The detection of SSTR 2A and SSTR 5 expression in tumor tissue of patients with advanced ACC, as well as the study of feasibility of using prolonged somatostatin analogs are promising in the treatment of patients with high receptor expression, however, further research is required.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The problem of childbearing in patients with myasthenia gravis (MG) is extremely important, since the disease most often affects women in the reproductive period. Has not yet been determined neither the prognostic criteria for myasthenia exacerbation during pregnancy, nor the predictors for the development of the transient neonatal myasthenia gravis (TNM). The article analyzes the literature data from the first descriptions of pregnancy in patients with myasthenia and TNM until the present days. The evolution of the concept of the role of a high titer of antibodies to acetylcholine receptors (anti-AChR Ab) in the development of exacerbations of MG in the mother and TNM in her newborn is shown. The role of Ab against γ-subunits of AChR in the development of arthrogryposis and THM is discussed. The importance of planning the pregnancy in myasthenic mothers is emphasized. These observations show that the same woman has either a favorable course of MG with the birth of a healthy child, or has a severe exacerbation until the postpartum myasthenic crisis with the birth of baby with TNM depending on quality of remission before pregnancy. Based on the literature data and own experience, the indisputable role of thymectomy in the prevention of exacerbations of MG and TNM is shown. Own observation of cases of TNM demonstrates the crucial role of neostigmine test in the recognizing of «floppy baby» syndrome. For the first time in Russia, a study of anti-fetal/anti-adult AChR Ab ratio in the umbilical cord blood was conducted. For the first time in the world, a unique case of the birth of a healthy child in a couple of patients with juvenile MG is presented. The husband suffering of the severe refractory MG with elevated titre of anti-AChR Ab up to 20.8 nmol/l and a lot of congenital stigmas of dysembryogenesis. The wife had a mild course of MG. She was carefully prepared for pregnancy by thymectomy and glucocorticoid-therapy and had a stable condition for more than 10 years at the time of pregnancy. The titer of anti-AChR Ab was relatively low (9.0 nmol/L), however, the pool of anti-AChR Ab in the umbilical cord blood mainly contained anti-fetal AChR AB (92%). This example shows that it is the quality of remission of the mother's MG at the time of pregnancy determines the course of the disease during pregnancy and the risks of TNM. This case allows us to consider genetic factors as secondary and once again emphasizes the autoimmune nature of myasthenia gravis.

© 2018, SPb RAACI. The theory of polyetiological tumorigenesis is one of the most important theories of carcinogenesis. A great place in this theory is given to the role of inflammatory component, which is implemented via the factors of innate immunity. I.e., toll-like receptors (TLRs), chemokines and their receptors are related to innate immunity. Activation of TLRs may lead to regress or progression of cancer process. It is known that TLR3, TLR5, TLR7, TLR9 have the greatest anti-Tumor effect due to the dendritic cells (DCs)-mediated activation of type I T helpers, activation of M1-Type macrophages and Treg inhibition. Stimulation of TLR2 and TLR4 exerts an activating effect upon the tumor, by the MyD88 hyperactivation and secretion of IL-6 and TNFα, but exact mechanisms are not fully understood. In addition to TLRs, chemokines and their receptors have a great influence on the cancer development. It is shown that CCL2, CCL4, CCL17, CCL22 and CXCL12, which are secreted by cancer microenviroment, activate chemotaxis of tumor cells. It is also known that the chemokines activate CXCR4 and CCR7 (expressed by tumor cells) thus leading to metastasis. It is shown that there is an association between some gene polymorphisms of TLRs', chemokines and their receptors, and development of cancer. Thus, we may conclude that the role of TLRs and chemokines is important in oncogenesis. Further study of innate immunity factors influencing tumorigenesis are important for finding new approaches to cancer therapy and new potential vaccines against cancer.

© 2018 Stavropol State Medical University. All Rights Reserved. Type I Diabetes mellitus (DM), or insulin-dependent diabetes, is the most common endocrine pathology among children and teenagers. The purpose of this study is to research the content of 1A melatonin receptor and antibodies to it in blood serum of children and teenagers. We examined 71 children and teenagers aged 1.9 to 17 years. We measured the content of 1A melatonin receptor and antibodies to it in hemolymph using an immunofluorescence assay test system (IFA). We found that the lowest levels of the 1A melatonin receptor were prevailing in children with a serious condition at the DM decompensation stage, median values were diagnosed in children in a state of moderate severity, and the maximum quantities are fixed in children against the background of the compensation of DM. The obtained data confirm the hypothesis about the possible involvement of the corpus pineale (epiphysis) in the pathogenesis of Type I Diabetes mellitus.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Results of investigation of the analgesic activity of the natural recombinant peptide PT1, which specifically binds to P2X3 receptors, are presented. The test for hypersensitivity provoked by complete Freund's adjuvant (CFA) showed evidence of the analgesic activity of PT1 peptide in CD-I mice after single intravenous administration in a dose range of 0.01-1 mg/kg.

© 2018 John Wiley  &  Sons Ltd. While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.

© 2018 Bentham Science Publishers. Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders. In this concern, the involvement of UT II in the pathophysiology of many processes determines the perspectives for the development of blockers of urotensin receptors for the treatment of the aforementioned diseases. It is important that even today this kind of perspective is feasible due to the synthesis of a series of GPR14 blockers. The objective of this review is to discuss current molecular mechanisms of biological activity, regulatory functions of UT II, its role in the pathogenesis of different nosologies, as well as analysis of the possible routes of exposure to GPR14 as potential therapeutic targets.

Background: The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions.

Conclusion: In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.