Bulletin of Experimental Biology and Medicine最新文献

The involvement of DNA synthesis in the mechanisms of long-term memory reconsolidation in edible snails trained for conditioned food aversion was investigated. Administration of nucleoside analogs, such as 5-bromo-2'-deoxyuridine or 3'-azido-3'-deoxythymidine, which inhibit DNA synthesis, 1 h before or 1-3 h, but not 5 h after reminder with the conditioned stimulus led to memory impairment. One day after the inhibitor application and memory reactivation, a weakly expressed memory impairment (amnesia) was observed, which progressed over the next few days to the complete disappearance of behavioral memory expression. In snails with formed aversive memory for two food conditioned stimulus, a specific memory impairment was observed only for the stimulus that was paired with the presentation of an inhibitor during the reminder, while the memory for the other non-reactivated conditioned stimulus remained intact. It is suggested that DNA synthesis in the brain plays a specific role in the genetic mechanisms of reconsolidation and maintenance of long-term conditioned food aversion memory in snails.

The changes in astrocytes and their role in the development of brain diseases can be identified by morphological analysis of tissue specimens, in particular, by immunohistochemical detection of glial fibrillary acidic protein (GFAP). The study presents analysis of GFAP expression in white matter astrocytes of deceased newborns depending on the duration of the postmortem period. Autopsy material of the brain tissue obtained from 48 deceased newborns was divided into 8 groups depending on the duration of the postmortem period. Immunohistochemical analysis was performed with antibodies to GFAP in tissue samples taken from the superior and inferior brain areas relative to the position of the body stored before autopsy. The area of GFAP+ staining per field of view was determined in the white matter using an image analysis system. Morphometric analysis revealed a decrease in the mean values of the area of GFAP+ staining, i.e. the number of fibrotic astrocytes and their processes decreased with increasing the duration of the postmortem period. The mean areas of GFAP+ staining in the superior and inferior areas of the white matter did not differ significantly between the groups. The identified changes reflect the development of nonspecific postmortem changes which should be considered when taking tissue samples for molecular biological studies and in differential forensic diagnosis with lifetime lesions and diseases.

In adult male mice with high (HR) and low (LR) resistance to hypoxia, on days 21 and 28 after subcutaneous injection of Lewis lung carcinoma cells, a morphological and morphometric study of the primary tumor nodes and metastases in the lungs was carried out. Peripheral blood parameters and subpopulation composition of blood cells, the expression of genes responsible for the development of inflammation (Nfkb, Il1b, Il6, Tnfa, Il10, and Tgfb) and the response to hypoxia (Hif1a) in the liver were also assessed. The tumors were detected in 84.6% HR and 91.7% LR mice. The mitotic index of tumor cells in the subcutaneous nodes of HR animals was statistically significantly higher. The metastases area on days 21 and 28 did not differ. In animals of both groups, an increase in the absolute number of leukocytes, monocytes, and granulocytes, a decrease in the hemoglobin content and the absolute number of erythrocytes in the peripheral blood were detected on day 28 of the experiment. Only in LR animals, an increase in the absolute number of CD11b⁺ monocytes was found on day 28 of the experiment in comparison with the control group. The expression of Hif1a, Nfkb, Tnfa, and Tgfb genes in the liver of LR animals was higher than in HR mice, which attested to more pronounced systemic inflammatory response. These data should be taken into account when developing new approaches for the treatment of neoplastic disorders.

This work presents the method of synthesis and physicochemical characterization of isothiourea and cinnamic acid original derivative α-cyano-4-hydroxycinnamate 1-cyclohexanoy-l-2-ethylisothiourea (T1114). In studies of the cytotoxic and antitumor activity of T1114, it has been found that the combination in one molecular structure of NOS-inhibitory fragment (1-cyclohexanoyl-2-ethylisothiourea) and a fragment inhibiting monocarboxylate lactate transporters (MCT) (α-cyano-4-hydroxycinnamic acid) does not modify the cytotoxic activity of bifunctional NOS/MCT-inhibitor T1114 in vitro. But in vivo inhibition of NOS and MCT is able to realize effects on the tumor microenvironment and hypoxic tumor cells. Such structural and functional modification has significantly extended the antitumor activity of the new NOS/MCT inhibitor. The bifunctional compound not only realized a more pronounced antitumor effect, but also prevented the development of hypoxic adaptation in solid Ehrlich carcinoma and acquired the ability to overcome the resistance of mouse cervical cancer (RShM-5). Therefore, the combination of NOS-inhibitory, anti-vasculogenic and hypoxia-oriented toxic effects can create new opportunities in antiangiogenic therapy of malignant neoplasms.

In an experiment on Wistar rats, a Heymann's active nephritis model was reproduced. After the chronic course of the disease was confirmed, we compared the effectiveness of single systemic and local transplantation of allogeneic cultured stromal cells of the mononuclear fraction of the bone marrow. Both methods of cell therapy reduced clinical manifestations of active Heymann's nephritis: proteinuria decreased and glomerular filtration rate increased 30 days after cell administration. At the histological level, signs of the inflammatory process manifested in an increase in the number of CD68⁺ cells. Thus, in the case of autoimmune glomerulonephritis, two transplantation methods provide a comparable level of correction of functional disorders in Heymann's active nephritis model.

The functioning of the ventricular myocardium in hypertrophic cardiomyopathy (HCM) under high hemodynamic load leads to depletion of its resources and is associated with the risk of developing a dilated stage. In patients with HCM, the cardiomyocytes of the interventricular septum are hypertrophied, the proportion of cardiomyocytes in which myofibrils constitute less than 50% of the sarcoplasm volume increases with increasing the cardiomyocyte length and correlates with echocardiographic signs of left ventricular obstruction. These cardiomyocytes are characterized by ultrastructural signs of synthetic activity. In the myocardium of patients with HCM, single cardiomyocytes with "critical" loss of myofibrils and nonspecific degenerative changes corresponding to the picture of irreversible changes in the cardiomyocyte ultrastructure were revealed. The presence of cardiomyocytes with this ultrastructural phenotype is an early marker of exhaustion of the compensatory capabilities of the myocardium in HCM.

We studied the association of polymorphisms in the aminopeptidase N gene (ANPEP) with the development of diabetic retinopathy and nephropathy in patients with type 2 diabetes mellitus (T2DM). DNA samples from T2DM patients (n=1425) were genotyped for 23 single nucleotide polymorphisms (SNPs) using the MassARRAY system. Associations of SNP rs13380049 of the ANPEP gene with a lower risk of diabetic retinopathy (OR=0.54, 95%CI 0.36-0.82, p=0.0032) and nephropathy (OR=0.66, 95%CI 0.44-0.99, p=0.048) were found in T2DM patients. In addition, SNP rs25653 was associated with retinopathy, and polymorphisms rs6496608, rs72756574, rs9920421, and rs4932143 were associated with diabetic nephropathy. The study demonstrated the contribution of ANPEP gene polymorphisms in the determination of microvascular complications in T2DM patients.

The rheographic parameters of the segments of brachial and femoral arteries were measured in situ after a 14-day-long hindlimb unloading (HU) of rats. HU significantly increased electrical impedance Z of a segment of femoral artery indicating its constriction; in parallel, HU resulted in a decreasing trend of Z of a segment of brachial artery attesting to its dilation. In both arteries, HU significantly or as a trend decreased the swing ranges of active and passive pulsations, respectively. BP reduction during bloodletting induced transition from passive to active pulsatile mode in the femoral artery only in 33% experimental rats in contrast to 87% control ones. We suppose that degradation of active pulsatile mode is responsible for the negative influences of microgravity and weightlessness on blood circulation. The study determined the rheographic parameters that reliably reflect changes in the functional activity of arteries after chronic redistribution of hydrostatic load.

The effectiveness and safety of two types of samples based on a biocompatible polymer material made of methacrylic oligomers (Reperen) as a potential antiadhesion pericardial barrier were evaluated in in vitro and in vivo experiments. Two kinds of samples, reinforced with a polyamide mesh and without reinforcement, were used. In in vitro experiments, no adhesion and aggregation of human fibroblasts to the test samples were detected. In in vivo experiments, the samples implanted to rats into the thigh muscles were easily separated from the surrounding tissues 1, 2, and 3 weeks after implantation, being weakly fixed only in the area of the edges. Histological examination at week 2 after implantation revealed no differences between the experimental and control groups. At week 1 and 3, fibrosis and inflammation were more pronounced in animals of the control group (with simulated implantation). The properties demonstrated by both samples of Reperen barriers (with and without polyamide mesh reinforcement) in vivo and in vitro allow considering them as a potential antiadhesion pericardial barrier for clinical use.