Bulletin of Experimental Biology and Medicine最新文献

Formation of abdominal adhesions is accompanied by the synthesis of collagen monomers by fibroblasts and deposition of type I and III collagens. This process is regulated by various factors, including TIMP-1, MMP-1, TGFβ, IL-10, and IFNγ. Oxidized dextran prevents fibrosis, adhesion formation, affecting the functional state of macrophages and fibroblasts. Collagen formation and fibroblasts in abdominal adhesions of Wistar rats were studied against the background of intraperitoneal administration of oxidized dextran. Electron and light microscopy and immunohistochemical method (collagen I, TIMP-1, MMP-9, FGF) were used. Administration of oxidized dextran prevented tropocollagen secretion into the extracellular matrix, the assembly of collagen I fibers, while functional activity of fibroblasts was preserved, and was accompanied by fibroblast apoptosis. Macrophages formed contacts with fibroblasts and phagocytosed apoptotic cells.

Na,K-ATPase activity is critical for maintaining electrogenesis and skeletal muscle function. Isolated rat diaphragm muscles were studied after 3-h high-altitude hypobaric hypoxia (HAH, corresponds to an altitude of 6000 m) in a pressure chamber. LPO activation was observed over 24 h after HAH; no significant changes in other markers of oxidative stress and energy metabolism were detected. During this period, stable hyperpolarization of the sarcolemma developed due to increased electrogenic activity of the α2-Na,K-ATPase isoform, while the total muscle level of the α2-subunit protein remained unchanged. Our findings may have practical implications for developing measures to maintain skeletal muscle functions during high-altitude adaptation.

Mice were subjected to vestibular stimulation (rotation at 80 rpm for 8 h) and behavioral disturbances and morphological changes in the Deiters' vestibular nuclei were studied 1 h and 2, 5, and 7 days after stimulation. Horizontal and vertical motor activity decreased after long-term vestibular stimulation and recovered after 1 day. Short- and long-term disturbances in the morphology of Deiters' neurons and neuropil were detected. Disturbances in the structure of neurons were no longer detected 2 days after stimulation, while disturbances in myelinated axons in the neuropil persisted for up to 7 days. These disturbances manifested by abnormal water distribution and pronounced damage to the myelin sheath. It is assumed that long-term edema of myelinated axons is a target for therapeutic intervention in diseases associated with axonal demyelination.

Pancreatic stellate cells (PSCs) are involved in the homeostasis maintenance in the pancreas, but upon activation, they are capable of excessive production of extracellular matrix proteins, which can aggravate the course of the pathological process, in particular diabetes. The changes in the functional activity of PSCs in the acinar and islet parts of the pancreas in rats with experimental type 2 diabetes mellitus were assessed by the expression of GFAP and α-SMA markers, as well as by the intensity of collagen proportion. During the development of experimental type 2 diabetes mellitus, PSCs are activated in the pancreas as evidenced by enhanced expression of α-SMA accompanied by increased collagen production. We revealed a direct correlation of the levels of glucose and HbA1c with relative collagen content in the islets and the number of α-SMA+ cells. The results obtained can further contribute to the development of therapeutic strategies for the treatment of type 2 diabetes mellitus.

We studied the effects of exogenous melatonin (administrated ad libitum at a concentration of 4 mg/liter in drinking water for 4 weeks) on the differentiation of B lymphocytes (PAX-5⁺) and apoptosis (Casp3⁺) of spleen cells in outbred laboratory mice kept under conditions of natural photoperiod, constant darkness, or constant illumination. Constant darkness increased the number of B-lymphocyte precursors and caspase-3 lymphocytes in the lymphoid follicles of the spleen. Constant light exposure reduced the number of B lymphocyte precursors, increased the number of Casp3⁺ lymphocytes and the content of caspase-3 and transcription factor PAX-5 in these cells. Melatonin administration under artificial photoperiods (24/24 and 0/24 regimens) reduced the number of Casp3⁺ cells and increased the number of PAX-5⁺ cells in the white pulp.

A recombinant modified human transferrin (N413D and N611D) was produced by the Pichia pastoris strain pPIC9pGAPZalpha-short_hTFNG (Yst-TFNG2). A multi-step protocol for isolation and purification of recombinant transferrin was developed achieving the target protein yield of 70.29% and a purity of at least 95%. Structural correspondence of the recombinant transferrin to the natural protein was confirmed by mass spectrometry and circular dichroism analysis. Functional analysis demonstrated the protein's ability to bind and release iron ions, as well as support the proliferation of eukaryotic cells.

We studied the effect of gaseous transmitter H₂S on the cytokine-producing activity of perivascular adipose tissue in rats with metabolic syndrome modeled by high-fat high-carbohydrate diet for 12 weeks. It was shown that the serum concentration of H₂S and the level of H₂S biosynthesis enzyme (CSE) were decreased in animals with metabolic syndrome. The secretory activity of perivascular adipose tissue cellular elements after high-fat high-carbohydrate diet is characterized by increased synthesis of proinflammatory cytokines (IL-6, TNFα, MCP-1) and decreased production of anti-inflammatory IL-10. It was found that exogenous H₂S donor (NaHS, 100 μM) shifted the balance of cytokines secreted by the perivascular adipose tissue by reducing the concentration of proinflammatory mediators, thereby exerting an anti-inflammatory effect on the perivascular adipose tissue.

Male Wistar rats were subjected to mild, moderate, and heavy physical exercises (10 swimming sessions), after which they were euthanized (immediately or 30 days after the last session). Animals of the experimental groups received meldonium (100-120 mg/kg of body weight) with food for 10 days of swimming. Heavy exercise led to the development of degeneration, necrotic patches, and cellular infiltration in the liver and a decrease of the TGF-β1 level. In 30 days after the last swimming session, an increase in both the level of TGF-β1 in the cytoplasmic fraction and the expression of the tgfb1 gene were observed. The level of TGF-β1 increased by 1.8 times against the background of meldonium treatment and decreased by 1.6 times in 30 days; tgfbl expression also decreased by 1.3 times in comparison with that in rats exposed to a similar exercise without meldonium (p < 0.05). The use of meldonium against the background of heavy physical exercise contributed to the achievement of gene expression and cytokine levels approaching the target values observed in intact animals and prevent severe alterative changes in the liver.

We studied changes in the content of obscurin and the corresponding mRNA in the left ventricle of rat heart during the development of isoprenaline-induced myocardial injury. Myocardial injury was induced by subcutaneous injection of β-adrenoreceptor agonist isoprenaline hydrochloride at a dose of 150 mg/kg of body weight twice with a 24-h interval. On day 14, the animals were euthanized. An increase (by 28.7%; p ≤ 0.01) in heart weight, as well as an increase (by 17.7%; p ≤ 0.01) in the heart-to-body weight ratio in rats after isoprenaline injection were observed, indicating the development of cardiac muscle hypertrophy. Western blotting with antibodies specific to the N-sequence of rat obscurin previously produced by us revealed a 1.2-fold decrease (p ≤ 0.01) in the content of the A-isoform (880 kDa) of this protein in the left ventricle of the rat heart after isoprenaline injection. This decrease was observed against the background of elevated content (4.2-fold; p ≤ 0.01) of obscurin mRNA. The role of reduced obscurin content in the deterioration of heart function during the development of isoprenaline-induced myocardial injury is discussed.

The anxiolytic effects of Gly-His-Lys-Pro-Gly-Pro peptide (GHK-PGP) and its proline-containing analogs were studied in a test with punished behavior. Peptides Gly-His-Lys (GHK), Pro-Gly-Pro (PGP), GHK-PGP, Gly-His-Lys-Gly-Pro (GHK-GP), and Gly-His-Lys-Pro (GHK-P) were used. Anxiolytic activity was assessed in the Vogel conflict test. The peptide GHK had no anxiolytic effect, while PGP and GHK-PGP produced an anxiolytic effect in certain doses. Presumably, the anxiolytic effect of the peptide GHK-PGP is determined by the action of PGP in the absence of the blocking effect of GHK. The peptides GHK-P and GHK-GP also had anxiolytic effects, which may indicate the presence of anxiolytic activity in various proline-containing amino acid sequences attached to GHK.