Bulletin of Experimental Biology and Medicine最新文献

The protective properties of argon-oxygen mixture were studied in the culture of M-22 human fibroblasts, piglet thymus cells, and rat brain cells. To induce damage to cell membranes, 200 μM H₂O₂ and 500 μM acetic acid were used. The cells were exposed in the presence of a gas mixture containing 70% argon and 30% oxygen (ArgOx 70/30) at 37°C for 6 h. The ArgOx 70/30 mixture produced no toxic effect on the cells of all studied cultures. In culture of M-22 fibroblasts, acetic acid-induced cell death decreased by 1.5-1.9 times under the influence of ArgOx 70/30 and the cell membranes remained better preserved. In none cultures, ArgOx 70/30 mixture significantly protected cells from hydrogen peroxide-induced damage. Piglet thymus culture cells demonstrated very high resistance to high concentrations of hydrogen peroxide and acetic acid, while rat brain cells, on the contrast, had low resistance.

We studied the distribution and survival of mesenchymal stem cells (MSCs) transplanted within a fibrin hydrogel into the spinal cord of immunocompetent rats without spinal cord injury (SCI) and with contusion SCI within the first hours after injury. MSC migration was monitored by MRI, and cell survival was assessed by immunofluorescence and immunohistochemistry on spinal cord sections. It was shown that transplanted allogeneic MSCs remain viable for at least 7 days in case of intrafocal administration 30 min after experimental contusion SCI and for at least 28 days in case of subdural and intramedullary transplantation into the intact spinal cord. MSCs are predominantly located at the injection site. Thus, our data demonstrate that allogeneic MSCs transplanted into the SCI site in the acute phase can survive for at least 7 days without migrating into surrounding tissues.

Since hypergravity and simulated microgravity alter the morphological and physiological properties of the heart and the quantity of gene transcripts for mechanically gated channels (MGCs), it was hypothesized that cardiomyocyte sensitivity to stretching would be altered. Using the whole-cell patch-clamp technique during stretching of isolated cells, we have demonstrated that hypergravity in rats increases cardiomyocyte sensitivity to stretching, which manifests as a pronounced increase in the ion currents through MGCs in response to cell stretching. On the contrary, simulated microgravity substantially decreases cardiomyocyte sensitivity to stretching, which manifests as a significant reduction in stretch-induced currents through MGCs. Considering previously published data, we believe that these effects are based on the respective increase or decrease in MGC gene transcripts.

Here we studied the effect of partial hepatectomy in patients with liver cancer (n = 48) on the level of serum iron and whether it can be corrected with iron supplementation therapy (IST; daily for 9 days). To identify whether the rapid decline in serum iron occurs only after hepatectomy, we studied this parameter in patients after pneumonectomy (n = 41). The hematocrit (HCT) and hemoglobin (HGB) levels were assayed by complete and differential blood counts, serum transferrin (TRF) and serum iron levels were measured by immunoturbidimetry and TPTZ (2,4,6-tri-(2-pyridyl)-5-triazine) method, respectively. After partial hepatectomy, the levels of serum iron and TRF in peripheral blood significantly decreased in comparison with the levels before surgery (p < 0.001). No significant elevation of serum iron and TRF was observed immediately after termination of IST, although these levels increased significantly 30 days after the onset of the therapy. Similar changes were observed in the control group in the same time points after the surgery, so IST exerted no positive effect. In contrast, both the incidence of intensive care unit admission and iron overload were higher in the IST group in comparison with the control. Serum iron sharply decreased after partial hepatectomy, which could be mainly due to the decrease in TRF. IST after hepatectomy did not improve HGB level. Thus, IST after partial hepatectomy was ineffective.

Disturbances in calcium signaling and, in particular, store-operated calcium entry are associated with a wide range of diseases, including neurodegenerative, oncological, and autoimmune pathologies. Inhibitors of store-operated calcium entry have a neuroprotective effect and suppress metastasis, which makes store-operated channels an attractive target for drug design. Previously, we showed that 1,2,3,4-dithiadiazole derivatives are negative modulators of store-operated calcium channels that are normally activated by STIM1 and STIM2 proteins. Here, we studied the specificity of action of one of the most effective compounds of this class, 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide, on STIM1- and STIM2-mediated store-operated calcium entry and concluded that it blocks calcium entry through store-operated channels activated by both STIM1 and STIM2.

Virulence genes are often present on pathogenicity islands (PAIs) and serve as markers for specific pathogenic types of Escherichia coli. We studied the prevalence of PAIs associated with diarrheagenic (DEC PAI markers) and uropathogenic (UPEC PAI markers) E. coli among strains isolates from various sources, considering their phylogenetic group affiliation and pathogenic potential. DEC PAI markers were detected in 41.7% of fecal E. coli (FEC), 46.4% of avian pathogenic E. coli (APEC), and 84.6% of UPEC. UPEC more frequently contained PAIs carrying the siderophore biosynthesis gene clusters in comparison with FEC or APEC. UPEC PAI markers were equally prevalent in ExPEC groups (APEC and UPEC); however, PAIs exhibited greater diversity in uropathogenic strains. A positive correlation was found between the prevalence of the PAI genes and phylogenetic group B2, as well as the number of virulence genes present.

We studied functional state of liver mitochondria in 5-6-week-old SHR rats. Parameters of respiration and oxidative phosphorylation were assessed. The obtained data were compared with the results of the Western blotting of protein subunits forming the mitochondrial respiratory chain complexes in the liver. The activity of antioxidant enzymes (SOD, catalase, and glutathione peroxidase) and the rate of H₂O₂ production were also examined in comparison with the control (WKY rats). An increase in the level of respiratory-chain complex V protein subunit, as well as a decrease in the activity of major mitochondrial antioxidant enzymes in SHR rat liver, was shown. The obtained results indicate the appearance of pathophysiological changes in the mitochondrial function in the liver (the organ that is not a primary target of the disease) of 5-6-week-old SHR rats (the age of first manifestations of arterial hypertension). These changes should be considered in future research into the pathogenesis of essential hypertension at its early stages.

We studied the expression of checkpoint molecules in monocyte subsets and monocytic myeloid-derived suppressor cells (M-MS) and the effect of homeostatic cytokines (IL-2, IL-7, IL-15) on the expression of PD-1/PD-L1 and Tim-3/Galectin-9 by myeloid cells. Monocytes and M-MS were shown to express PD-1 and Tim-3, and the proportions of PD-1⁺ monocytes and M-MS increased in multiple myeloma patients. Homeostatic cytokines enhanced the expression of inhibitory receptors (especially PD-1) by donor myeloid cells, the greatest effect was observed in M-MS. In addition, homeostatic cytokines increased PD-L1 expression in CD14⁺CD16^- monocytes and M-MS, and Galectin-9 in M-MS. Increased expression of checkpoint molecules by myeloid cells under the stimulation of IL-2, IL-7, and IL-15 is discussed as a feedback mechanism of T-cell homeostatic proliferation induced by lymphopenia.

Alloxan has been proposed as a diabetogenic agent due to its ability to destroy pancreatic β cells through the formation of free radicals, leading to oxidative stress, which has a significant role in the etiology and pathogenesis of diabetes and its complications. In Wistar rats with alloxan-induced diabetes, the levels of liver glycogen in the liver and the levels of total lipids and triglycerides in the liver, adipose tissue, and muscles were assessed over two months. Experimental diabetes was accompanied by a decrease in the levels of liver glycogen and an increase in the levels of triglycerides and total lipids in the liver, muscles, and adipose tissue. Treatment with insulin and metformin led to improvements in these parameters, with insulin having a more pronounced effect. The glycogen levels in the liver in rats receiving insulin was significantly higher than in animals treated with metformin (2767.86 and 1075.40 mg/100 g of tissue, respectively). The total lipid content in the liver significantly decreased against the background of insulin treatment compared to metformin (5730.90 and 8486.87 mg/100 g of tissue, respectively). Metformin administration led to an 11.9% reduction in liver triglycerides, while insulin reduced them by 25%. Oral administration of metformin for two months did not affect liver glycogen levels in alloxan-induced diabetic rats. Insulin injections increased liver glycogen levels and reduced total lipid and triglyceride levels in the liver. The hypolipidemic effect of these drugs appears to be due to the regulation of metabolism at the liver and adipose tissue levels.

The anti-parkinsonian activity of benzolsulfonamide selective MAO-B inhibitors was evaluated in a model of experimental parkinsonism in white mice (systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP). Six candidate compounds (laboratory codes S6-S8 and S11-S13) were analyzed. Rasagiline was used as the reference drug. Only compound S13 was comparable to rasagiline in preventing the development of rigidity and hypokinesia in animals and surpassed the reference drug in correcting emotional and behavioral activity.