Bulletin of Experimental Biology and Medicine最新文献

The expression of somatostatin receptors (SSTRs) of types 1, 2, and 5 was studied in the small intestine of rats from different age groups (1, 10, 20, 30, 60 days, and 2-year-old) using Western blotting. The expression of SSTR1, SSTR2, and SSTR5 increased in the first 30 days of life, but decreased in older rats compared to 2-month-old animals. These findings suggest that there is differential expression of SSTRs during age-related development of the small intestine. Further studies will determine the role of individual SSTRs in the growth and development of target organs.

Extracellular Ca²⁺ is the first ligand that has been confirmed to function by activating the calcium-sensing receptor (CaSR), a member of G-protein coupled receptors. CaSR controls not only calcium homeostasis, but also plays a pivotal role in many cellular processes such as cell proliferation and apoptosis; moreover, it is implicated in the development of cardiovascular diseases. TGF-β/Smads signaling pathway is a classical pathway of renal fibrosis. Here we used a culture of mesangial cells to evaluate the mechanisms of the renoprotective effects of Ca²⁺. We found that Ca²⁺ inhibits TGF-β-induced phosphorylation of Smad2 and deposition of fibronectin (FN), in turn, down-regulation of FN and phosphorylation of Smad2 was closely related to the degradation of Smad2 through the proteasomal pathway. We found that Ca²⁺ only downregulates the expression of Smad2 at the protein level, but has no effect on its gene expression. However, Ca²⁺ could downregulate TGF-β-induced expression of FN both at the protein and gene level. Hence, Smad2 acts as a transcription factor of FN, and its degradation definitely inhibits the expression of its target gene FN.

The effect of optical stimulation at a frequency of 10 Hz (OS_10Hz) on temporal parameters of sensorimotor activity in healthy subjects (n=32) was studied. The expression of the activation response was determined by the ratio of spectral power values (SPα2, μV²) of the high frequency (10-13 Hz) subrange of the α-rhythm of the initial EEG with closed and opened eyes and the frequency of the maximum α-peak (IAPF). A test for simple motor reaction time was performed under normal and OS_10Hz conditions. According to the change in the variability of simple motor reaction time (SD_SMRT) under OS_10Hz compared to the normal conditions, the subjects were classified into two groups: those who showed a decrease (group 1) and those who showed an increase (group 2) in SD_SMRT. The subjects of group 1 had significantly higher IAPF (in the O1 lead with eyes closed) and activation reaction intensity (in the O2, O1, P4, P3, and F3 leads) compared to the subjects of group 2. The obtained data suggest that OS_10Hz changes the parameters of psychomotor reactions of an individual, and the direction of changes is mediated by individual features of the initial EEG.

Using magnetic resonance imaging (MRI) with radial scanning, images of intact rat lungs and rat lungs with pulmonary hypertension were obtained. The retrospective gating method was applied to construct images of rat lungs during inspiration and expiration phases. Lung volumes at both respiratory phases, relative tidal volume, and the percentage of lung lesions were calculated. Lung volumes at inspiration and expiration were greater by ~4 and ~18%, respectively, and the relative lung tidal volume was lower by ~2.8 times than in intact rats. Constructed fractional ventilation maps showed a ~2.6-fold decrease in ventilation values in the pathological area. Thus, the application of the retrospective gating method allows detecting changes in lung volumes and ventilation, confirming the presence of pathology and its impact on the respiratory function.

It was previously found that the severity of LPS-induced systemic inflammatory response (SIRS) in rats is determined by resistance to hypoxia and the level of Hif1a expression. Individual differences in the level of Hif1a and NFkb expression in the liver were studied in relation to the severity of inflammatory and immune reactions in LPS-induced SIRS in rats without previous placement in a ventilated decompression chamber. During the early periods after SIRS modeling, rats with high expression of the Hif1a and NFkb genes associated with increased expression of pro- and anti-inflammatory cytokines are identified. These animals have a high blood level of corticosterone, low number of neutrophils in the interalveolar septa, and a predominance of T cells over B cells in the peripheral blood. The obtained data can be used to develop new approaches to the individual prediction of the severity of sepsis and SIRS in intensive care units, which will increase the effectiveness of therapy and reduce mortality rate.

In vitro and in vivo effects of mesoporous silica nanoparticles (MSN) on the functional activity of platelets were studied in experiments on white rats. MSN particles, neither uncoated nor coated with calcium alginate, induced spontaneous platelet aggregation when added to platelet-rich plasma, but significantly enhanced ADP-induced platelet aggregation. Subcutaneous administration of uncoated and calcium alginate-coated MSN resulted in increased maximum size and rate of platelet aggregate formation 1 day post-injection. In contrast, cellulose-coated MSN had no significant effect on platelet function in vitro or in vivo, suggesting their potential as carriers for targeted drug delivery.

We studied the effect of reprogrammed CD8⁺ T cells (rT cells) from the bone marrow of intact mice on tumor cells and neovasculogenesis in mice with orthotopic Lewis lung carcinoma (LLC). Reprogramming of T cells was carried out using a MEK inhibitor and a PD-1 blocker; the targeting of rT cells to tumor cells was achieved by preincubation with LLC cell lysate. It was shown that the antitumor effect of rT cells was based on apoptosis of tumor cells. In addition, cell therapy reduced the number of endothelial cells (CD45^-CD309⁺) and angiogenic cell precursors (CD45^-CD117⁺CD309⁺), mesenchymal stem cells (CD45^-CD31^-CD34^-CD44⁺), myeloid (CD45⁺CD34⁺CD31^-) and non-myeloid (CD45⁺CD34^-CD31^-) fibrocytes, and leukocytes (CD45⁺) in the lungs and increased their number in the blood. Thus, rT cells impaired the recruitment of neovasculogenic cells to the lung. The antitumor effects of rT cells are superior to those of naive CD8⁺ T cells. The proposed reprogramming method can be useful in developing effective approaches to the therapy of lung cancer, as it allows obtaining cytotoxic rT cells capable of reducing the activity of neovasculogenesis.

Micromycetes from the genus Alternaria are commonly found in plant food raw materials, and their produced emerging mycotoxins (EMT) pose a risk to human health. Based on polyphase taxonomy, we studied the species composition of the Alternaria spp. population in samples of Russian grain and berries; non-toxinogenic species of Alternaria of the Infectoriae section and toxinogenic species of the Alternaria section were found. Using in vitro HPLC-MS/MS, a high potential for EMT production was revealed in strains from the Alternaria section: alternariol and alternariol methyl ester, tenuazonic acid, altenuene, and tentoxin. These findings indicate that species of the Alternaria section play a significant role in the contamination of plant foods with EMT. The proposed algorithm for in vitro analysis of toxin formation can be implemented in screening for toxin-producing species within the Alternaria spp. population, allowing the differentiation of chemotypes and an expansion of the understanding of the biodiversity within the Alternaria spp. population.

Changes in the lipid and carbohydrate metabolism, adipokines, and growth factors during the development of metabolic disorders were studied in three mouse models: C57BL/6 (alimentary obesity), db/db (leptin-resistant obesity), and NOD (diabetes mellitus) lines. In the group of alimentary obesity, moderate fatty infiltration of the liver and hypertrophy of the adipose tissue, hyperglycemia, and increased concentrations of adiponectin, transforming growth factor β1 (TGF-β1), leptin, and cholesterol were detected. In the group of leptin-resistant obesity, multiple pathological changes in tissues, severe hyperglycemia and hyperleptinemia, hyperinsulinemia, and reduced concentrations of triglycerides, adiponectin, myostatin, and TGF-β1 were detected. In NOD mice, reduced number of insulin-positive β cells, hyperinsulinemia, and a decrease in adiponectin, TGF-β1, leptin, and myostatin concentrations were detected.

We studied the effect of acteoside on a model of human corneal epithelial cells (HCEC) injury induced by H₂O₂. HCEC were divided into 4 groups and cultured for 24 h in normal medium (intact and control groups, respectively), or in a medium containing DMSO or 160 μM acteoside (DMSO and acteoside groups, respectively). Then, H₂O₂ solution was added to HCEC for 4 h, except for intact cells. The cell viability was assessed by the CCK8 method to determine the working concentrations of acteoside and H₂O₂ for further experiments. Quantitative PCR and Western blotting were used to determine the effect of acteoside and H₂O₂ on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH:quinone oxidoreductase-1 (NQO-1), and cyclooxygenase-2 (COX-2). The effects of these agents on cell proliferation were assessed by staining with 5-ethynyl-2'-deoxyuridine (EdU). It was found that acteoside protected HCEC against H₂O₂-induced damage by inhibiting the expression of Nrf2, HO-1, NQO-1, and COX-2.