Bulletin of Experimental Biology and Medicine最新文献

We compared the pharmacokinetic parameters of liposomal emulsion and aqueous solution of Mexidol after intravenous injection to rats at a dose of 50 mg/kg. The concentrations of Mexidol in blood plasma and homogenates of the lungs, liver, kidneys, testes, and ovaries were measured 30, 60, 120, 240 min, 24 and 48 h after administration by HPLC. The liposomal Mexidol in contrast to its aqueous solution quickly disappeared from systemic circulation (a 5-fold decrease in plasma concentration was noted as soon as 4 h after administration) and was predominantly absorbed and retained for a longer period by the liver and lungs: after 24 h, the concentration of liposomal Mexidol exceeded that of its water-soluble form by 14.2 times in the liver and by 63% in the lungs. In the testes, the concentration of liposomal Mexidol exceeded that of its water-soluble form during the first 4 h postinjection: by 4 times after 1 h and by 2 times after 4 h, whereas in the ovarian tissues, the same concentrations were observed after administration of liposomal and water-soluble forms. In the gonadal tissues, the water-soluble form of Mexidol was retained longer than its liposomal form.

We studied the sensitivity of clinically significant (opportunistic) bacteria to blood serum fraction with a molecular weight <100 kDa containing antimicrobial peptides and proteins. The degree of damage to cytoplasmic membranes of bacterial cells was assessed by a spectrophotometric method. A total of 129 bacterial isolates belonging to 46 species, 19 genera, 13 families, 8 orders, 4 classes, and 3 types were studied. The mean sensitivity varied from -5.2 to 36.6%. The sensitivity depends on the structure of bacterial cell wall: higher sensitivity was demonstrated by taxonomic ranks related to gram-negative bacteria (median 19.1%) and lower values were observed in gram-positive bacteria (median 9.3%) (p<0.01). Among all orders, Lactobacilliales showed the lowest sensitivity (3.6%). Ranking of the studied species by their sensitivity showed that 7 of the first 15 species with sensitivity >19% are among to the leading causative agents of sepsis.

A new approach has been developed to study the pharmacokinetics of 2,6-diisobornyl-4-methylphenol, a phenolic antioxidant, after intragastric administration at a dose of 10 mg/kg to male Wistar rats with ischemia/reperfusion liver injury. The control group consisted of rats without pathology. A catheter previously implanted into the jugular vein of the animals, allowed repeated blood sampling and monitoring of the pharmacokinetic profile of the substance in each animal. Pharmacokinetic studies usually involve healthy animals, but the ischemia/reperfusion injury of the liver disrupted its functions, potentially altering drug metabolism and pharmacokinetics. Analysis of actual blood plasma samples confirmed the effectiveness of the proposed approach: changes in the pharmacokinetics of the phenolic antioxidant were revealed during liver ischemia/reperfusion injury in rats.

Infectious and inflammatory processes during pregnancy in women provoke maternal immunity activation (MIA) and increase the risk of neuropsychiatric disorders in children. These disorders can lead to neurodegenerative diseases later in life. To study these effects, we evaluated the morphological and molecular biological changes in the hippocampus and prefrontal cortex of male and female Wistar rats on the 1st day of postnatal ontogenesis after LPS-induced MIA. The level of calprotectin in the blood serum of postpartum rats, the number and morphological properties of microglial cells in the hippocampus, and the expression of proinflammatory, stem, and adaptation markers in fragments of the prefrontal cortex in offspring of both sexes were determined. It was found that LPS-induced MIA had a negative effect on the developing offspring, with an increase in the level of expression of Nfκb and App in the prefrontal cortex of newborns being observed. Sex differences in morphological and molecular biological changes in the brains of newborn Wistar rats were also revealed: the number of microglial cells increased in male rats, while the number of ramified microglial cells decreased in female rats. In addition, only in females, the expression levels of the mRNA markers for stem cells, Sox2 and Sox9, decreased, while the expression level of Hif1α, which has a neuroprotective effect, increased only in males. These data may explain the differences in the incidence of neurodegenerative diseases among elderly patients of different sexes.

Progressive toxic liver fibrosis in Wistar male rats was characterized by the migration of CX3CR1⁺ and CD34⁺ cells from the bone marrow, accompanied by a mild increase in their numbers. From weeks 3 to 5 and 9 to 13, the number of CX3CR1⁺ cells remained approximately the same. The area occupied by CD34⁺ cells increased by 2 times (p<0.001) only by the end of the experiment. At week 3, the correlation between Cxcl12 and Notch2 mRNA was lost, while at week 9, a correlation of Cxcl12 with Notch1 and Notch2 was observed. From week 11 onwards, a correlation of Cxcl12 with Notch2 was revealed and a correlation with Notch1 disappeared. miR-3558-3p was correlated with Cxcl12 mRNA level at the stages of progressive fibrosis and nodular remodeling of the liver parenchyma. The greatest number of miRNAs showed direct and inverse correlations of moderate to medium strength, with Cxcl12 gene at the stage of complete cirrhosis. The mRNA levels of Cxcl12 and Yap1 showed a significant correlation with each other throughout the experiment. This suggests that they may be involved in the process of cell migration from the bone marrow to the liver and play a role in fibrosis and cirrhosis. They could be considered as potential targets for the development of new treatments.

Angiogenesis is regulated by various types of endothelial cells: tip cells, stalk cells, and phalanx cells. In this study, the changes in cerebral angiogenesis and the characteristics of angiogenesis in the prefrontal cortex of Alzheimer's disease (AD) mice were investigated. AD was induced by injection of β-amyloid into the hippocampus. The animals underwent cognitive testing, and their brains were analyzed using immunohistochemical techniques to evaluate angiogenesis. The results showed an increase in the proliferation of endothelial cells and altered ratio of tip, stalk, and phalanx cells. Vascular branching and density in the prefrontal cortex were decreased, indicating an unproductive form of angiogenesis in AD. Obtained results highlight the link between changes in angiogenesis and cognitive decline, confirming the importance of vascular dysfunction in AD progression.

We studied the effects of recombinant human angiogenin on in vitro proliferation, migration, apoptosis, and secretion of human skin fibroblasts (FB) and endothelial cells (EC; EA.Hy926). The most potent stimulation of migration and proliferation of EC and FB was observed at angiogenin concentration of 125 ng/ml in a serum-free medium. Angiogenin had little effect on apoptosis/necrosis of EC and FB. It promoted IL-1β production by EC in a serum-free medium and did not affect FB. Angiogenin had the opposite effects on the production of TNFα and IL-10 by cells: it suppressed the production of these factors by EC in a serum-free medium and enhanced their production by FB in media with and without serum. In a serum-free medium, VEGF production by EC increased and by FB drops. NO production by EC in response to angiogenin stimulation did not depend on the culturing conditions, while NO production by FB increased in complete culture media. Thus, the presence of FCS in the culture medium considerably modulated the effect of angiogenin.

Chromosomal composition of micronuclei of phytohemagglutinin-stimulated peripheral blood T lymphocytes in women chronically exposed to radiation due to their residence in the Techa riverside settlements in the Sothern Urals (mean age 76.4±1.2 years, mean cumulative dose for the red bone marrow 1.4±0.3 Gy) was analyzed using the cytochalasin-block micronucleus assay and multicolor fluorescent in situ hybridization (mFISH). Exposed women demonstrated an increase in the number of chromosomes eliminated from cell nucleus, but the frequency of micronuclei did not differ from that in the comparison group. High variability of the frequency of micronuclei was also noted in the group of exposed women. In all the women, X-chromosome and autosomes 2, 16 were significantly more often eliminated than other chromosomes.

The study examined the quantitative variations in the levels of pro-oncogenic miRNAs (miRNA-21, miRNA-27a, and miRNA-221) and tumor-suppressive miRNA-429 in blood serum and lymph of female Wistar rats with breast cancer after photodynamic therapy and controls (without treatment). The levels of pro-oncogenic miRNA-21 and miRNA-221 in the blood serum and lymph increased in the control group. Photodynamic therapy significantly reduced the levels of these miRNAs, suggesting the effectiveness of the treatment. The levels of pro-oncogenic miRNA-27a in the blood serum and lymph of both groups were multidirectional. The levels of tumor-suppressing miRNA-429 decreased significantly in the control group and remained low after photodynamic therapy. Therefore, miRNA-21 and miRNA-221 in the blood serum and lymph can be used as markers of the effectiveness of photodynamic therapy.

The rapid formation and high stability of addictive memory are the main causes of frequent relapse of alcohol and drug diseases, which limits the possibility of complete recovery and necessitates the search for ways to disrupt the formation or enhance the extinction of addictive memory. The present work shows that myelopeptide MP5 accelerates the extinction of morphine-induced conditioned place preference in C57BL/6 mice and supports synaptic plasticity in the hippocampus, while MP2 produced no such effects.