Bulletin of Experimental Biology and Medicine最新文献

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.

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.

The structure of the nucleoid observed after standard aldehyde fixation did not correspond to modern ideas about its spatial organization: DNA strands are not seen in Staphylococcus aureus and appear stuck together (2-15 nm) in Pseudomonas aeruginosa. The Ryter-Kellenberger (RK) fixation involving incubation in 1 % osmium tetroxide (pH 6.0) followed by 0.5 % uranyl acetate (pH 3.0) effectively preserves DNA strands (2 nm). The RK method also revealed additional details of the envelope structure in gram-positive and gram-negative bacteria. However, ribosomes, observed as spherical particles in aldehyde-fixed samples, were not visualized in the cytoplasm of S. aureus after RK fixation. The study provided a new information on the ultrastructure of bacteria, which is necessary for understanding the mechanisms of antibacterial compounds effects.

Hyperpolarization-activated currents blockade (I_f) (ZD7288, 10^-9 M) had a multidirectional effect on the left ventricular developed pressure in sham-operated (SO) rats and decreased this parameter in rats with long-term consequences of myocardial infarction (lcMI). The I_f blocker (10^-5 M) increased the left ventricular developed pressure in SO rats and decreased it in the lcMI group. Heart rate of the isolated heart after I_f blockade decreased in both experimental groups. I_f blockade (10^-9 M) produced multidirectional changes in coronary flow (CF) in the lcMI group and decreased CF in the SO group. The maximum concentration of the blocker reduced CF in both experimental groups. The duration of contraction of the isolated heart decreased after addition of I_f blocker at a minimum concentration, while the maximum concentration of I_f blocker increased this parameter in both groups. The I_f blocker increased the duration of relaxation of the isolated heart at both concentrations in all groups, the greatest changes were observed in the SO group. The duration of the contraction cycle during I_f blockade (10^-9 M) increased in the SO group and did not change significantly in the lcMI group. At a concentration of 10^-9 M, the blocker increased the duration of the contraction cycle in both groups.

Listeria monocytogenes, a causative agent of sapronoses, can enter the human body through ingestion of contaminated marine hydrobionts, posing a significant public health risk. Mono- and polycultural biofilms of microorganisms were detected spectrophotometrically. The study demonstrated that metabolites from marine-origin Bacillus bacteria stimulate the formation of L. monocytogenes monocultural biofilms, as well as mixed biofilms of L. monocytogenes and the marine bacterium Micrococcus luteus. In mixed biofilms of L. monocytogenes and a marine Flavobacterium bacterium genus, Bacillus megaterium metabolites exhibited both stimulating and inhibitory effects, depending on concentration. These findings suggest that Bacillus-derived metabolites can enhance the growth and proliferation of L. monocytogenes in biofilms, potentially influencing the epidemic risks in recreational areas of Peter the Great Gulf.

The antimicrobial activity of Escherichia phage Ec1-7 and Escherichia phage Ec2-7 was evaluated both separately and in a phage cocktail. The combination of phages significantly extended the spectrum of lytic activity and effectively inhibited the growth of bacteria, including strains with emerging resistance. The phage cocktail exhibited higher efficacy (3.6-4.8 lg(CFU/ml)) in comparison with monophages (1.3-2.8 lg(CFU/ml)) during a 6-h incubation period: it prevented secondary bacterial growth and reduced the likelihood of resistance development. Our findings corroborate the potential of phage cocktails in combating antibiotic-resistant strains.

According to current knowledge, hypoxia is a key mechanism mediating the detrimental effects of prenatal alcohol exposure on the nervous tissue. However, comparative analysis of these interrelated conditions has only been partially addressed. We conducted a morphometric analysis of fetal brain tissue affected by chronic alcohol exposure and hypoxia. A decrease in the specific area of neuroblasts, glioblasts, and microvascular elements was found. Hypoxia promoted enlargement of neuroblasts and their differentiation into immature neurons, whereas alcohol exposure led only to a decrease in their number. In the brain subjected to hypoxia, glioblasts were characterized by size variability with a general trend toward reduction, while alcohol had no significant effect on their size. Both experimental groups showed a decline in vascular density.

The studied substances of the prostate extract have vasomotor activity of varying degree. The substance-mixture Prostatilen at concentrations of 2 and 5 μg/ml causes a positive chronotropic effect increasing the frequency of contractions by 23.7% (p ⩽ 0.01) and 37.6% (p ⩽ 0.01), respectively. The substance-powder Samprost did not affect motor activity of lymphatic vessels at a concentration of 2 μg/ml and inhibited the frequency of contractions by 6.7% (p ⩽ 0.05) at a concentration of 5 μg/ml. The substance Biofac at a concentration of 2 μg/ml has a negative effect on the motor activity of lymphangions changing the parameters of contractile activity in different directions, and at a concentration of 5 μg/ml it inhibits the contractile activity of lymphatic vessels (a 14.2% decrease in contraction frequency; p ⩽ 0.05).