Bulletin of Experimental Biology and Medicine最新文献

Capillary-like network (CLN) formation on Matrigel is a classical model for assessing the angiogenic properties of cells, though the underlying mechanisms vary across cell types. We identified two distinct CLN formation patterns and evaluated how each type characterizes the angiogenic potential of cells. Only endothelial cells (ECs) capable of elongating during CLN assembly on Matrigel exhibited angiogenic activity in other in vitro models (2D and 3D). Transcriptional profiling of ECs in a 2D co-culture with MSCs showed that CLN formation coincided with the upregulation of genes encoding tight junction proteins, Notch pathway components, and syndecan-2. Stromal cells are also capable of forming CLNs on Matrigel and in 3D model, underscoring their physiological role in tissue remodeling and homeostasis through network assembly.

Anxiety-like behavior in rats was assessed using a model of chronic unpredictable mild stress of varying duration, with prior administration of LPS. Chronic unpredictable mild stress induced biphasic changes in anxiety levels: an initial reduction during the early phase of stress exposure followed by a significant increase at later stages. Pre-treatment with LPS modulated the trajectory of anxiety development under conditions of chronic unpredictable mild stress: it exacerbated anxiety-like behavior during the early phase but attenuated its progression in the later stages. These findings suggest promising insights for the development of novel therapeutic strategies targeting stress-induced behavioral disorders.

The study examined the relationship between ultradian rhythms of body temperature (BT) in young (1-month-old) Djungarian hamsters (Phodopus sungorus) and fluctuations in atmospheric pressure (AP). A stable positive correlation was identified between BT variations and AP changes, most prominently during the animals' daily active phase. This association was especially pronounced during periods of rising AP. Harmonic analysis revealed synchronized rhythmic components in both BT and AP within the 12-30-min period range. However, experimentally induced (artificial) oscillations in AP did not elicit corresponding changes in BT, indicating that AP fluctuations alone do not drive the observed physiological rhythms. These findings suggest that the natural 12-30-min AP oscillations observed under stable weather conditions likely serve as external markers of an underlying biotropic factor that modulates the animal activity rhythms rather than acting as a direct causal stimulus.

Using real-time PCR, changes in the gene expression of TNFα and its receptor TNFRSF1A, factors involved in the regulation of inflammatory processes and synaptic plasticity, were examined in the hippocampus, frontal cortex, and cerebellum of adult male Wistar rats following either the formation of long-term spatial memory in the Morris water maze or forced swimming stress using a comparable time protocol. An increase in Tnfa gene expression was observed in all three brain regions. In contrast, elevated Tnfrsf1a expression was detected only in the hippocampus and frontal cortex but not in the cerebellum of both trained and stressed rats in comparison with the intact controls. Notably, Tnfa expression in the hippocampus of trained animals was significantly lower than that in untrained stressed rats. Furthermore, Tnfrsf1a expression showed a negative correlation with the success rate of long-term memory formation. These findings suggest the existence of adaptive mechanisms associated with long-term memory formation that act to suppress proinflammatory signaling pathways in the brain.

Coagulation hemostasis parameters were assessed in non-human primates of the genus Macaca spp. specifically Macaca mulatta and Macaca fascicularis (age 1-34 years) housed in open enclosures at the Kurchatov Complex of Medical Primatology, National Research Centre "Kurchatov Institute" under humid subtropical climatic conditions. A high degree of interspecific variability in the measured hemostatic parameters was observed among sexually mature individuals of both species. Statistically significant differences were found in the mean values of coagulation parameters between immature and mature animals. Furthermore, in the age group of 20 years and older (classified as aged animals), significant sex-dependent differences in the mean values of the studied hemostasis indicators were also detected. The quantitative reference ranges obtained in this study can serve as a baseline for interpreting hemostasiological data in laboratory studies involving these primate species.

We studied the effect of hypoxic stress on the efficiency of intercellular communication through gap junctions (GJ) in cultured endothelial cells. The cells were maintained under conditions of normoxia (20% O₂; group 1), after which GJ were either pharmacologically blocked (group 2), exposed to hypoxic stress (< 0.1% O2, 24 h; group 3), or simultaneously blocked and exposed to hypoxic stress (group 4). Carbenoxolone, a specific GJ inhibitor, was used to suppress connexin-mediated signaling. Hypoxic stress induced a 2.1-fold increase in HIF1A expression (p ⩽ 0.05) and stimulated directed cell migration (by 1.6 times), without significantly affecting the formation of capillary-like structures. In contrast, inhibition of GJ reduced both directed and random migration (by more than 2 times; p ⩽ 0.05), completely suppressed the formation of capillary-like networks, and was accompanied by reduced expression of HIF1A (by 1.6 times) and GJA1 (by 2 times; p ⩽ 0.05). Hypoxia moderately increased the proportion of necrotic cells without substantially influencing overall viability, whereas GJ blockade reduced necrosis, possibly due to disruption of intercellular transmission of death signals. These findings indicate a critical role of functionally active GJ in mediating the hypoxia-induced angiogenic response of endothelial cells, including modulation of key gene expression, migration, and capillary-like structure formation in vitro.

The systemic effects of thermo-photobiomodulation (TPBM) on mesenchymal stem cells (MSCs) and influence of repeated sessions in vivo were studied. The impact of local laser irradiation (λ = 970 nm, moderate power) of rat tibial bone marrow on MSC counts in other bone marrow organs and in the spleen was evaluated. A significant temporary increase in MSCs counts after TPBM was found not only in the irradiated area, but also in distant tissues. Repeated irradiation enhanced MSC growth in the injured area compared to single session, highlighting the potential of repeated TPBM for regulating stem cell activity. These findings open prospects for developing new cell therapy methods aimed at accelerating tissue and organ regeneration.

We studied the effectiveness of poloxamer-188 solution (Myotive) administered orally and intravenously at a dose of 48 mg/kg to female BALB/c mice before and after inoculation of colon carcinoma. After oral and intravenous administration of the poloxamer, active tumor necrosis and body weight loss for this reason were observed; a decrease in the tumor volume and normalization of the differential blood cell count and hematological parameters were also seen. Thus, poloxamer-188 is a promising antitumor agent presumably affecting the modified lipid bilayer of tumor cells.

We studied the effect of the water-soluble fraction of the extract containing β-glucans from Pleurotus ostreatus (oyster mushroom) on myelosuppression and colitis induced by 5-fluorouracil (5-FU) in male BALB/c mice. A decrease in the toxic effect of 5-FU was observed after single oral administration of the extract at a dose of 500 mg/kg. Treatment with 5-FU led to body weight loss by 7% relative to the initial value on day 21, while after addition of the extract with β-glucans, we observed an increase in body weight by 1% by that time in parallel with normalization of blood erythrocyte count. In mice treated with the extract containing β-glucans, the severity of the toxic effect of 5-FU on the colonic mucosa was significantly reduced on day 21: 99.7 ± 1.2 vs 91.8 ± 1.7 viable crypts in animals receiving 5-FU alone (p < 0.01). The results of the study prove the possibility of using β-D-glucans of P. ostreatus extract for the prevention and treatment of gastrointestinal side effects of antitumor drugs.

Aluminum ions are an immunostimulating agent and a promoter of the production of ROS that play a key role in the pathogenesis of age-related diseases. The severity of morphological signs of neurodegeneration caused by chronic intake of AlCl₃ aqueous solution (100 mg/kg, 60 days) and mRNA expression of genes encoding the neuroprotective factor BDNF and the antioxidant enzyme GPX4 were compared in adult and aged male Wistar rats. In comparison with the adult control rats, aged animals showed a more pronounced immunohistochemical reaction with antibodies to tau protein (pTau) in the entorhinal and temporal cortex. In adult animals of the experimental group, a significant increase in the aluminum level in the hippocampus and temporal cortex was observed, which was accompanied by enhanced Gpx4 mRNA expression. In aged rats of the experimental group, no significant accumulation of aluminum in the brain was observed in comparison with the corresponding control, while the expression of Bdnf and Gpx4 was markedly reduced and the content of intracellular amyloid fibrils and pTau⁺ inclusions in neurons, mainly localized in the entorhinal and temporal regions, was higher. The obtained data complement previous studies and confirm the high relevance of this model for further study of the mechanisms of initiation and progression of neurodegenerative processes in humans.