Bulletin of Experimental Biology and Medicine最新文献

Innate immune cells have the ability to acquire non-specific immunological memory (NIM), which provides resistance to a variety of bacterial and viral infections. Experiments in vitro and in vivo have verified the hypothesis that the farnesyl pyrophosphate synthase inhibitor (aminobisphosphonates) can potentiate BCG-induced NIM. The aminobisphosphonate zoledronate induced the NIM phenotype in human monocyte cultures and provided nonspecific protection against staphylococcal infection in mice. Additionally, zoledronate significantly enhanced BCG-induced NIM, resulting in a synergistic protective effect. The phenomenon of potentiation of NIM/anti-infectious resistance discovered by us can form the basis for designing powerful universal vaccines of a new type.

In 24-month-old male Wistar rats, the endothelium-dependent (ED) and endothelium-independent (EI) responses of the arteries of the cranial pia mater (CPM) of branching orders I-V were studied by vital microscopy 30 days after the modeling of myocardial infarction. Sham-operated animals were used as a control. In both groups, a distinct response of the CPM vessels of different branching orders to vasodilators was observed: in pharmacological tests (acetylcholine, nitroglycerin), a dependence of the ED or EI vascular reactivity on the diameter of the arteries was found. In orders I-II branches, the myogenic ED response predominates, and the EI response of the vessels prevails in orders IV-V branches. In order III branches, both mechanisms were approximately equally developed. In most cases, the vascular reactivity and numerical density of arteries that changed their diameter were significantly lower in rats with myocardial infarction compared to control animals. Thus, in myocardial infarction, systemic disorders of the ED and EI reactivity of the CPM vessels of different diameters caused by endothelial dysfunction have been identified; the combination of these disorders with age-related changes determined rapid depletion of adaptive reserves and increased circulatory hypoxia in the brain. These processes lead to neurodegenerative changes, primarily in the oxygen-sensitive neurons of the frontal cortex, and to cognitive impairments.

The aim of this study was to evaluate the quality of manual segmentation of cerebral infarction lesions in experimental animals with modeled brain infarct based on magnetic resonance imaging compared to an automated artificial intelligence approach. For automated infarct segmentation, an artificial intelligence system with the Swin-UNETR architecture was used, while manual segmentation was performed by four independent researchers. It was shown that manual segmentation exhibits significant variability, especially when small brain infarct lesions are analyzed. The obtained data emphasize the need for standardizing methods and applying automated systems to improve the accuracy and reproducibility of the results.

The clinical significance of the total area of mitochondria index in the right atrial appendage cardiomyocytes was evaluated. The index was calculated as the ratio of the total area of interfibrillar mitochondria to the area of the interfibrillar space (S_MT/S_IFS). A total of 39 micrographs of cardiomyocytes from 12 patients with heart failure (left ventricular ejection fraction LV EF<50%) and with obstructive multivessel coronary artery disease were analyzed. The results of the electron microscopy study were compared with the main echocardiography parameters and the functional status of the patients. It was found that the computed S_MT/S_IFS index was associated with general functional status according to the 6-min walk and cardiopulmonary exercise tests.

The correlation between the total activity of the complement system (TACS) and the content of modified LDL (mLDL) in blood serum when modeling microgravity in Earth conditions was evaluated. Healthy volunteers were placed in a state of antiorthostatic hypokinesia for 21 days. Microgravity in ICR mice was modeled by tail suspension for 14 days. TACS, activity of the alternative pathway (in humans), and the content of mLDL in serum from volunteers and mice were measured by turbidimetry. On day 7 of antiorthostatic hypokinesia, volunteers had a significant increase in TACS, which persisted until day 21. The content of mLDL in blood serum increased significantly on day 7. In experiments with mice, TACS increased significantly on day 14, and mLDL content decreased significantly. The limitation of mobility, which is an integral part of microgravity modeling, causes an increase in the overall hemolytic activity of the complement system in both humans and laboratory animals, indicating a response to significant physiological stress.

The receptor mechanism of the antinociceptive effect of the diterpene alkaloid songorine was investigated in an experiment on mice. Antagonists of peripheral opioid, κ-opioid, and cannabinoid 1 receptors eliminated the analgesic effect of songorine. These findings suggest that these receptors are involved in the antinociceptive action of songorine.

Therapeutic efficacy of olfactory ensheathing cells and type I collagen administered separately or in combination was studied in a model of chronic spinal cord injury in rats. The introduction of collagen hydrogel at a concentration of 4 mg/ml with and without olfactory ensheathing cells into spinal cord cysts reduced cyst volume and restored hindlimb motor function. The introduction of collagen hydrogel at both concentrations (1 and 4 mg/ml) with and without ensheathing cells stimulated remyelination of damaged nerve tissue. The results show that further study of this bioengineered preparation, as well as other combinations with cells or hydrogels is promising for the treatment of spinal cord injuries.

The effects of low- and medium-dose X-rays on mitochondrial function in mesenchymal stem (stromal) cells (MSCs) were compared. Irradiation at a dose of 80 mGy did not lead to mitochondrial disorders in MSCs by all analyzed parameters, while 24 h after irradiation at a dose of 2000 mGy, damage to mitochondrial and nuclear DNA was recorded, as well as the initiation of replicative synthesis of mitochondrial DNA involving damaged molecules, which led to an increase in the level of heteroplasmy. The increased level of mitochondrial DNA heteroplasmy after irradiation at a dose of 2000 mGy was accompanied by a decrease in the expression of genes involved in the process of oxidative phosphorylation and regulating mitochondrial dynamics.

In the context of relevance and social significance of the problem of attention deficit disorder among schoolchildren, we performed 3D-visualization of the brain in children (n=17; age 9-12 years) and adolescents (n=16; age 13-15 years). We found correlations between fractional anisotropy of the white matter fiber tracts (reflecting the quantity of axons and myelinization) assessed by diffusion-weighted magnetic resonance imaging (dMRI) and attention indicators (accuracy and task completion time) in children and adolescents. The improvement of attention between the ages of 9 and 12 years (the second childhood period) was accompanied by an increase in fractional anisotropy in the corpus callosum, while the decrease of attention was associated with the increase in the level of anisotropy in the third segment of superior longitudinal fasciculus (SLF_III). The opposite results were obtained for adolescents. In both groups, the improvement in attention was associated with an increase in fractional anisotropy in the SLF_I. A relationship of the obtained results with the data on different terms of maturation of the median (earlier development) and lateral (later development) cerebral structures in ontogeny is discussed.

Nephroblastoma overexpressed protein (NOV, also named CCN3), a member of the CCN (Cy61, CTGF, and NOV) family, is a critical biological marker of the severity of acute respiratory distress syndrome (ARDS). However, no evidence has been presented that CCN3 directly affects acute lung injury (ALI) or ARDS. Intratracheal infusion of LPS is an established method to simulate sepsis and induce ALI. To examine the effect of CCN3 on ALI, we developed in vivo and in vitro models of this disease on mice and type II alveolar epithelial A549 cells, respectively. To further clarify the role of CCN3 in ALI, we constructed a CCN3 overexpression model based on plasmid transfection. The results showed that CCN3 expression was up-regulated in LPS-induced ALI both in vivo and in vitro; this effect was time- and dose-dependent. ELISA revealed that overexpression of CCN3 increased the levels of proinflammatory cytokines IL-1β and TNFα. Flow cytometry and Western blotting showed that overexpression of CCN3 increased the expression of proapoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2, thereby promoting apoptosis of A549 cells. The results suggest that CCN3 antagonists can inhibit progression of inflammation and the development of apoptosis in lung epithelial cells, thereby exerting a possible therapeutic effect in ALI.