Type 2 diabetes mellitus (T2D) is one of the most common endocrine diseases in the world. It is characterized by dysfunction of pancreatic β-cells, insulin resistance, and hyperglycemia. Despite numerous studies on the pathogenesis and risk factors of diabetes, there is still no consensus on how best to diagnose, classify, and treat the disease. Accumulating evidence suggests that antidiabetic drugs can course unwanted side effects. S-15176 difumarate salt, a novel derivative of trimetazidine, inhibits the rate-limiting enzyme of fatty acid β-oxidation carnitine palmitoyltransferase I and has anti-ischemic properties, which makes it useful as an antidiabetic agent. Here, the effect of chronic treatment with S-15176 difumarate salt on the leukocyte formula and cytochemical indices of the peripheral blood neutrophils (myeloperoxidase activity, free phospholipids, and lysosomal cationic proteins) of C57Bl/6 mice in control and experimental T2D was studied. It was found that in the control group, S-15176 difumarate salt decreased the number of neutrophils containing lysosomal cationic proteins and the cytochemical coefficient of the cells. The treatment of diabetic mice with S-15176 had no significant effect on the activity of myeloperoxidase and free phospholipids in neutrophils. The results obtained suggest that the use of S-15176 difumarate salt as an antidiabetic drug does not induce changes in peripheral blood markers associated with immune-related adverse effects.
| Attachment | Size |
|---|---|
 3 Effect of the Trimetazidine Derivative S-15176 Difumarate Salt.pdf | 731.32 KB |
Photodynamic therapy is a minimally invasive cancer treatment modality based on the production of the reactive oxygen species by photoactive dye under light irradiation in the presence of molecular oxygen. During the development of the photodynamic reaction, various types of reactive oxygen species are formed, among which hydrogen peroxide is of the greatest interest since it can act as an extracellular and intracellular signaling molecule. Using a genetically encoded sensor of hydrogen peroxide, we have registered the development of oxidative stress in non-irradiated cells in response to local photodynamic exposure of a single cell using Photosens as a photosensitizer. The effect manifested when the cells were closely contacted to each other; if the irradiated cell was at some distance from the bulk of the population, the response of non-target cells was not observed. The oxidative stress in the irradiated cell is assumed to be the initiator of the signal transmission and triggering the response of non-target cells. That this response is more likely mediated by gap junction intercellular signaling. Нowever, the mechanisms involved in the propagation of damaging effects to cells outside the area of photodynamic exposure have to be further investigated.
| Attachment | Size |
|---|---|
| 2 Photodynamic Treatment сan Induce Enhanced Generation of Hydrogen Peroxide.pdf | 709.13 KB |
This work is devoted to the study of the individual characteristics of cerebral circulation, galvanic skin response and heart rate during mental, sensorimotor and sensory activity. In two groups, differing in the level of behavior control (precise and imprecise), a comparative analysis of behavioral and physiological indicators was carried out. Imprecise subjects before the test (readiness state) GO/NOGO showed higher indices of the tone of the arterioles and venules of the cerebral vessels in the basin of the carotid arteries. During the GO/NOGO trial, a more reactive increase in vascular tone was observed in the precise group, more pronounced in the right hemisphere. In the imprecise group, a higher level of mental stress was registered in terms of GSR and heart rate during mental counting. GSR was also more pronounced in this group when viewing images. The optimal and non-optimal types of information load portability are discussed.
| Attachment | Size |
|---|---|
| 1 Study of Neurophysiological and Hemodynamic Indicators.pdf | 369.78 KB |
Photodynamic therapy (PDT) is a promising approach in the treatment of various tumors. The presence of three essential components: a photosensitizer, a light source and oxygen is required for generating reactive oxygen species and subsequent tumor destruction. In this study, we investigated the cell death pathway induced by Photodithazine (PD) mediated photodynamic therapy (PD-PDT). We found that PD localizes in the endoplasmic reticulum and Golgi apparatus of cancer cells. Upon irradiation at 20 J/cm2, PD induced death of tumor cells at concentrations exceeding 100 nM. Based on dying cell morphology, exposure of phosphatidylserine to the cell surface, presence of phosphorylated form of mixed lineage kinase domain like pseudokinase (pMLKL) and protective action of pan-caspase inhibitor and inhibitor of receptor-interacting protein kinase 1 (RIPK1), we hypothesize that Photodithazine forces cells to enter mixed-type cell death with features of apoptosis and necroptosis.
| Attachment | Size |
|---|---|
| 7 Mechanisms of photodynamic killing of cancer cells by photodithazine.pdf | 1.13 MB |
We have explored the features of PPARγ2 gene alleles expression in elderly patients with comorbid conditions such as obesity and coronary artery disease. 140 patients of both sexes (54.3% men and 45.7% women) aged 60-89 were examined. The main group included 70 pts with CHD; the control group included 70 pts without CHD. Pro12 allele carrier state in the main group was 85%, and Ala12 allele carrier state – 15%. Pro12Ala and Ala12Ala genotypes, Ala12 allele were detected more often in patients with coronary artery disease than in the control group (p = 0.0008 and p = 0.0003, respectively). Pro12Ala genotypes (OR = 2.02, CI = 1.28–3.19, p = 0.003) and Ala12Ala (OR = 2.002, CI = 1.32–3.04, p = 0.0006) of Ala12 gene PPARγ2 carrier state increases the risk of CHD developing by 2 times. It was confirmed that nuclear PPARs are capable of controlling development, differentiation, metabolic homeostasis and reproduction. The role of various genotypes of the PPARγ2 gene in the regulation of lipid metabolism and angiogenesis in comorbid conditions in elderly patients may help to identify new methods of their treatment.
Currently, radionuclide therapy of tumors using sources of alpha and beta radiation is actively developing. However, the radiosensitivity of tumor cells has been studied mainly using acute gamma radiation. In this regard, studies aimed at determining the ranges of radiosensitivity of cells of various origins in relation to beta-emission radionuclides are gaining relevance. The study was carried out on A431, CHO and SK-BR-3 cell lines using beta-emission sealed sources Sr-90+Y-90. Cell viability was assessed via MTT-assay. Dose dependences were obtained for irradiating cells with a beta source: the LD50 range was from 17 to 19 Gy, and LD37 was from 24 to 36 Gy. It was shown that at the same dose of radiation, the percentage of viable cells relative to the control of 72 hours after irradiation is significantly less than after 24 hours. The revealed LD50 values for tumor cells under chronic beta-irradiation are higher than with acute gamma-irradiation, which should be considered when selecting doses during the development of potential radiopharmaceutical treatment. Decreased cell viability in response to beta radiation is due to both cytotoxic and cytostatic manifestations.
CuO in the form of micro- and nano-sized colloidal particles enters the human body from environment. The aim of the study is the identification of morphological changes in rat liver tissues during chronic oral intake of micro- and nanosized CuO by image analysis. The experiments were performed on 45 male Wistar rats (3 groups: experimental (nanosized CuO); comparison (micro-sized CuO); control (water without CuO)). Suspensions CuO were administered to the rats orally once a day. Quantitative morphological parameters were determined by pathomorphological examination and image analysis using the method of constructing Voronoi diagrams (the ratio of cells of various shapes); average cell area; the average size of the cell perimeter and the number of cells per unit area. As a result of the analysis by the constructing Voronoi diagrams, was found that the main part of the model cells corresponding to hepatocytes has the shape of a hexagon. In the control group, their share is 35.89%, in the experience group – 29.09%, and in the comparison group – 30.59%. The density of cells’ distribution in the comparison group is 7 times higher than in the control group; in the experimental group the same indicator is 4 times higher than in the control group. Collectively, the characteristics of morphological changes in liver tissue indicate greater toxicity of nano-sized copper oxide compared to its micro-sized analogue.
The world’s biggest killer is ischemic heart disease, responsible for 16% of the world’s total deaths. Since 2000, the largest increase in deaths has been for this disease, rising by more than 2 million to 8.9 million deaths in 2019. In recent years, many studies have shown that hydrogen has therapeutic and preventive effects in various human and animal disease models. In this study, we investigated the possible antioxidant effects of molecular hydrogen in erythrocytes and blood plasma in rats with the experimentally simulated chronic heart failure. We estimated the intensity of lipid peroxidation processes by the contents of diene and triene conjugates, Schiff bases, malonic dialdehyde, catalase activity. The results from this study suggest that inhalation of 2% molecular hydrogen leads to a decrease in pro-oxidant and an increase in antioxidant parameters. The results of this study provide the basic data for the mechanism research and application of molecular hydrogen in the future.
Achieving both deep penetration of photons into biological tissue and highly sensitive recording of optical probes' response are the key goals of non-invasive optical imaging. In comparison with the traditional fluorescence imaging in the visible (400–700 nm) and near-infrared (700–900 nm) regions, optical fluorescence imaging in the second optical tissue transparency window (1000–2300 nm) demonstrates low photon scattering, deeper penetration into the tissues and lower autofluorescence. In the present study, biocompatible upconversion nanoparticles with different contents of doping lanthanides, capable of luminescence in the visible and short-wave IR regions, were obtained and characterized. Also, targeted complexes based on Gd-containing nanophosphors were obtained as potential contrast agents for magnetic resonance imaging. Selective binding of targeted complexes to the surface of tumor cells expressing the HER2 receptor was shown.
Epilepsy affects around 1% of the population in the world. Thus, it is imperative that new more effective and safe treatments be found. In order to understand the nature of epilepsy, new and better animal models are needed in that they offer valuable resources for researchers. Such models provide an opportunity to characterize seizures in the whole organism, to understand the molecular basis of these processes and to test the effectiveness of treatments and therapies. In this study, we have shown that screening after chemical mutagenesis can be used as a tool to identify new genes that may be involved in the mechanism of epilepsy formation.
| Attachment | Size |
|---|---|
| 1 ENU mutagenesis as a tool for identifying novel mouse models of epilepsy.pdf | 663.99 KB |
Over the past two decades, developments in the field of nanobiomedicine have come a long way despite the unresolved hindrances. The creation and development of effective theranostic agents based on nanomaterials are urgent needs of modern medicine. Upconversion nanoparticles (UCNP) appear to be the most promising agents for developing theranostics due to their unique optical properties. There has been extensive research on new approaches to obtain stable colloids capable of prolonged circulation in the bloodstream, particularly with bovine serum albumin (BSA). The present work contributes to solving the problem of obtaining stable agents based on UCNP by coating water-soluble UCNPNOBF4 with a stable protein corona layer of BSA. The assembled nanocomplex is promising for usage as a diagnostic agent and is set for further investigation.
| Attachment | Size |
|---|---|
| The Assembly оf а Photoluminescent Nanocomplex Based оn Upconversion Nanoparticles.pdf | 487.42 KB |
Methylation of DNA cytosine bases is a key epigenetic modification that plays an important role in the regulation of gene expression and the formation of the epigenome. Numerous studies of the human genome show that there is a close relationship between DNA methylation, age and sex of a person. Until now, the popular model has been the linear change in the methylation level with age. Here we find a fundamentally different DNA methylation behavior, namely the nonlinear dependence of the methylation level on age. We identify CpG probes whose methylation changes exponentially with age or according to a power law, and perform Gene Ontology enrichment analysis of the latter. Our results are relevant to understanding how DNA methylation changes with age and the found nonlinear CpG sites can be used to construct new epigenetic clocks.
| Attachment | Size |
|---|---|
| DNA Methylation in Aging- Beyond the Linear Processes.pdf | 729 KB |
3D bioengineering constructs are currently a promising area of research in the regeneration of various tissues. In our work, several modifications of scaffolds based on hyaluronic acid glycidyl methacrylate are presented. Scaffolds have been tested for biocompatibility with nerve cells in an in vivo model of traumatic brain injury. Throughout the experiment, the neurological status of the animals was monitored, and at the end, a histological examination of the brain was carried out. It has been shown that scaffolds are non-toxic to nerve cells and reduce the development of neurological deficit in animals in the post-traumatic period. The possibility of using the scaffold with a lower biodegradation rate as a carrier of a therapeutic drug has also been demonstrated.
Decellularized matrices of animal organs can serve as a promising platform for creating highly relevant threedimensional in vitro models of tumor growth. In this work, the applicability of two decellularization protocols for obtaining the extracellular matrices of various murine organs was examined. The resulting decellularized matrices were characterized by visual integrity and preservation of the tissue architectonics. A high degree of the cellular component elimination was demonstrated while maintaining the basic structures of the extracellular matrix. From the point of view of convenience and ease of use, as well as the quality of the obtained matrices, the method based on the use of detergent sodium dodecyl sulfate and trypsin-aprotinin complex has demonstrated the greatest suitability. In the future, the developed protocol will be used to study tumor-matrix interaction and tissue-specific characteristics of growth and morphology of tumor cells.
An experimental trauma was performed for the studying of morphological changes characteristics of the brain under the action of neuroprotectors soon after the brain injury. The closed craniocerebral injury was modeled by the free fall of a load on the parietooccipital area of the brain. We made repeat studies of the influence of succinate medicaments (cytoflavin and mexicor) on histological examination and morphometric analysis of the microcirculatory bed of the cerebral cortex. The experiments were made on the 1st, 3rd, 7th, and 12th day after the traumatic brain injury. An experimental morphological study has established that the use of neuroprotetors after the trauma recovers of brain tissue and positively affects the angio- and cytoarchitectonics of the cerebral cortex in the posttraumatic period.
| Attachment | Size |
|---|---|
| Morphological Disturbances of Brain Structures in Traumatic Brain Injury.pdf | 1.05 MB |
ADHD is considered one of the most common neurobehavioral disorders of childhood and among the most prevalent chronic health conditions affecting school-age children. This makes research of psychophysiological correlates of ADHD very important. The aim of our pilot study was to find out the specific aspects of autonomic regulation of a sensorimotor activity in children with ADHD. To assess objectively the functional state dynamics of the children, the technology of event-related telemetry of the heart rate was used (cogni-nn.ru, Lobachevsky State University). This technology integrates the ApWay.ru Web platform for the controlled activation of primary cognitive functions. The conducted study allowed us to reveal some specific aspects of sensorimotor activity and autonomic regulation for children with ADHD. A digital map of psychophysiological status based on the integration of indicators of sensorimotor activity and event-related parameters of autonomic regulation can be an effective tool to increase the specificity, sensitivity and reliability of the diagnosis of ADHD in children.
| Attachment | Size |
|---|---|
| Heart and Mind Interaction for ADHD.pdf | 642.68 KB |
The development of clinical forms of infection and endoscopic changes in the gastric mucosa depends on the H.pylori genetic diversity in a given region. The aim of this work was to study the relationship of the genetic profile of H.pylori pathogenicity factors with clinical and endoscopic features of Helicobacter-associated gastritis in Nizhny Novgorod. A number of H.pylori pathogenicity genes of DNA isolates obtained by endoscopy from 151 patients with chronic H.pylori-associated gastritis (non-destructive, erosive, and atrophic) were studied by PCR. Results. In destructive processes in the gastric mucosa, the detection frequency of cagA, vacA s1 m1 genes and a combination of several pathogenicity factors, including iceA A1 and babA was higher than in other forms of gastritis. Atrophic gastritis is characterized by the genetic profile cagA and vacA s2 m2. Infection with several H.pylori strains is determined more often in erosive gastritis and atrophy of the gastric mucosa. Conclusions. In chronic gastritis in Nizhny Novgorod, a predominantly "European" character of the pathogen population structure was revealed - with a moderate content of the most pathogenic cagA, vacA s1-positive strains. Colonization of the gastric mucosa by H.pylori with a genetic structure containing pathogenicity factors cagA, vacA, babA, ice A2, in chronic H.pylori-associated diseases, it is a factor in increasing the severity, activity and prevalence of the inflammatory process, the appearance of signs of atrophy of the gastric mucosa. The greatest influence on these indicators is exerted by the presence of cagA and vacA s1 in the microorganism genome, as well as a combination of several pathogenicity factors.
| Attachment | Size |
|---|---|
| Genetic Variants of H.pylori in Different Forms of Chronic Gastritis.pdf | 474.77 KB |
Genomic instability is one of the biomarkers of aging. Studies show that the spontaneous level of chromosomal aberrations in lymphocytes increases with age. However, it is not yet fully understood whether there is an agedependent increase in genomic instability. The aim of this study was to establish the patterns of the influence of age on the level of chromosomal aberrations in human lymphocytes. For this purpose, the spontaneous frequency of chromosomal aberrations, mitotic activity and the number of aneuploidies in the lymphocytes of centenarians (people over 85 years old) were assessed. A standard cytogenetic research method was used. It was shown that the overall frequency of chromosomal aberrations in peripheral blood lymphocytes in centenarians was significantly higher than in the control group. It was revealed that there is a decrease in the mitotic activity of lymphocytes in the sample of centenarians, while the level of aneuploidies corresponds to the control group. It was also found that, despite the fact that the total number of aberrations increases with age, a decrease in the frequency of deletions is observed in the group of centenarians. No correlation was found between biological age and the frequency of aberrations.
| Attachment | Size |
|---|---|
| Features of Karyotype Changes in Centenarians.pdf | 398.86 KB |
The research of stress reaction under the influence of bee venom and immobilization on rat is made in this paper. It is demonstrated that the stress reaction is developed under the influence of both factors. However, it’s shown that the second phase of stress reaction connected with hypothalamo-pituitary-adrenal axis activation and glucocorticoid concentration increase predominates in case of bee venom injection. The revealed prolongation of the second, compensatory phase may define the organism resistance increase after the bee venom injection and bee venom therapeutic action.
| Attachment | Size |
|---|---|
| The Particularities of Organism Stress Reaction Development under the Influence of Bee Venom.pdf | 610.34 KB |
The possibility of using laser interference microscopy to explore the morphological and functional state of erythrocytes was studied. The possibilities of this method based on the rapid determination of the structure and physiological state of erythrocytes were shown. The analysis of erythrocytes by laser interference microscopy showed that erythrocytes have a typical biconcave discocyte shape. On erythrocytes’ surface, there is a slight heterogeneity due to the presence of membrane-bound proteins. The impact on erythrocytes of stress hormones caused changes in erythrocyte surface that were different from physiologically normal. Numerous loosening of the structure appeared on cell surface during erythrocyte incubation with cortisol. Incubation of cells with adrenaline caused a greater effect of erythrocyte membranes deformation which was expressed by the appearance of convex seals and spicules on the surface. The molecular mechanisms of membrane modifications arising under the action of adrenaline and cortisol were discussed. The results of the work may be interesting both for basic research of erythrocyte properties and for practical medicine.
| Attachment | Size |
|---|---|
| Research of Erythrocytes Membranes Change by Laser Interference Microscopy.pdf | 691.41 KB |
