Bulletin of Experimental Biology and Medicine最新文献

The activities of NAD- and NADP-dependent isocitrate dehydrogenases (NAD-ICDH and NADP-ICDH), NAD- and NADP-dependent glutamate dehydrogenases (NAD-GDH and NADP-GDH), and NAD- and NADP-dependent malate dehydrogenases (NAD-MDH and NADP-MDH) in ovarian veins lymphocytes in 183 women of reproductive age with pelvic varicose veins (PVV) and 30 women in the control group were determined. The indicators of intracellular enzymatic activity showed multidirectional changes with increasing severity of the disease. Compared to the control group, women with stage II of PVV had higher median values for lactate dehydrogenase (16.69), NAD-GDH (39.48), NADP-GDH (7.48), NADP-MDH (9.06) and lower values of NAD-ICDH (65.41). Women with stage III of PVV had lower median values for succinate dehydrogenase (9.27), NAD-MDH (26.19), and higher values for glucose-6-phosphate dehydrogenase (8.62), lactate dehydrogenase (24.67), NAD-GDH (63.81), NADP-MDH (21.05) compared to the control group. Studying the activity of NAD(P)-dependent dehydrogenases in lymphocytes at the local level during PVV allows us to evaluate the intensity and dynamics of local varicose veins progression, as well as to optimize its correction.

Highly specialized gap junctions play an important role in the interaction between endothelial (EC) and multipotent mesenchymal stromal cells (MSC). Inhibition of gap junctions with a specific inhibitor carbenoxolone attenuates the effects of the medium conditioned by MSC-EC co-culture on proliferation and migration of cultured EC. In conditioned medium from co-culture, the levels of angiogenic mediators (VEGF-A, FGF-2, MCP-1, etc.) were decreased, which apparently determines lower angiogenic effect of the conditioned medium on the growth of the vascular network in the chorioallantois membrane of quail embryo in ovo. Suppression of communication through gap junctions in associations of MSC and EC, the structural and functional units of physiological and reparative angiogenesis, can directly reduce the level of proangiogenic mediators in the microenvironment, which, in turn, can help to control the regulation of vascular function in pathologies.

Alzheimer's disease was induced in female Wistar rats by bilateral injection of β-amyloid fragment 1-42 into the hippocampal region. After 8 weeks, ensheathing cells of the olfactory mucosa were transplanted into the hippocampus at the same stereotactic coordinates. These cells survived for 8 weeks; large clusters of cells were observed on week 4. On weeks 3-5 after transplantation of ensheathing cells, experimental animals demonstrated a significant cognitive improvement (memory and spatial orientation). The obtained results create prerequisites for further studies of ensheathing cells as a potential cell product for personalized therapy of Alzheimer's disease.

We studied morphological features of the cerebellum in 14-day-old Wistar rats from reduced litters (the number of pups was reduced from 10-12 to 6 on the next day after birth). The control group comprised 14-day-old animals from litters of medium size (10-12 rat pups). Rats from reduced litters had greater body weight and brain weight. The weight of the cerebellum, together with the weight of the adjacent part of the brain stem and the thickness of cerebellar cortex also significantly exceeded the corresponding parameters in control animals. The thickness of the molecular layer of the cerebellar cortex and the numerical density of Purkinje cells in these rats did not differ significantly from the control. The thickness of the external granular (neurogenic) layer of the cerebellar cortex in rats from reduced litters was smaller. This can indicate accelerated reduction of this layer that persists in rats until days 20-22 of age. Numerical density of cells in the external granular layer of control and experimental animals was similar. Numerical density Ki-67⁺ cells in this layer, as well as GFAP⁺ glial cells in the granular layer of the cerebellar cortex in rats from reduced litters significantly exceeded the corresponding parameters in control animals. The cerebellum of rats from litters reduced 1 day after birth had a number of differences in important indicators reflecting the rate of its development during the neonatal and suckling periods of ontogeny.

Using produced polyclonal antibodies specific to the N-terminal sequence (residues 61-298) of rat obscurin, we investigated the isoform composition of this protein in 4 striated muscles: myocardium of the left ventricle, diaphragm, skeletal m. gastrocnemius (containing mainly fast fibers), and m. soleus (containing mainly slow fibers). The m. gastrocnemius, m. soleus, and diaphragm were found to have 2 giant isoforms of obscurin: a smaller A-isoform and a larger B-isoform. Their molecular weights were ~870 and ~1150 kDa in the diaphragm and m. gastrocnemius and ~880 and ~1130 kDa in m. soleus, respectively. The B-isoform to A-isoform ratio was 1:3 in the diaphragm and m. soleus and 1:4 in the m. gastrocnemius. In the left-ventricular myocardium, A-isoform of obscurin with a molecular weight of ~880 kDa was found. No other obscurin isoforms or their fragments within the molecular weight range of 10 up to ~800 kDa were revealed in the investigated rat striated muscles. The antibodies produced are recommended for research into qualitative and quantitative changes of giant obscurin isoforms in rat striated muscles in the norm and during the development of pathological processes.

We analyzed the state of neuroendocrine regulation and LPO-antioxidant defense systems in reproductive age women with metabolic syndrome (MetS), representatives of the Russian and Buryat ethnic groups. Compared to the corresponding control groups, women from the Russian ethnic group with MetS had elevated levels of thyroid-stimulating hormone and free androgen index (FAI) and reduced levels of sex hormone-binding globulin, while women from the Buryat ethnic group had increased levels of prolactin and FAI. Changes in the LPO system in women of the Russian ethnic group with MetS consisted in an increase in the levels of substrates with double bonds, TBA-reactive substances, and fat-soluble vitamins. Buryat women with MetS had a higher content of primary oxidation products and reduced levels of glutathione. The results of the study indicate a hyperandrogenic shift in the neuroendocrine regulation system, as well as compensatory influences from different parts of the antioxidant defense system in women of reproductive age with MetS, depending on their ethnicity. These findings indicate the need for assessing and monitoring the levels of these metabolites in women with MetS, considering their ethnicity.

We studied heart rate variability (HRV) and the concentrations of heavy metals in the heart tissue after 14-fold peroral administration of heavy metal salts: lead acetate (50 mg/kg), cadmium chloride (5 mg/kg), and their combination. After administration of lead, its concentration in the myocardium exceeded the control values by 1.2 times or did not change in case of combination with cadmium; after administration of cadmium, its concentration in the myocardium exceeded the control value by 6.1 times or by 2 times after combined administration. After lead administration, a moderate increase in HR, low values of stress and centralization indices, and an increase in the power in all ranges of the HRV spectrum were recorded. After cadmium intoxication, a tendency to a decrease in heart rhythm variability, a moderate increase in HR, stress and centralization indices, and an increase in the contribution of VLF waves in the HRV spectrum were observed. After combined administration, a pronounced increase in HR and stress index and a moderate increase in the centralization of heart rhythm control were recorded, which was similar to changes in HRV observed after administration of cadmium alone. In the experiment, the concentration of cadmium in the myocardium increased to a much greater extent than the concentration of lead. After lead administration, the autonomous type of regulation persisted and parasympathetic influences increased. Cadmium apparently acts as a stress factor and increases the role of sympathoadrenal influences and central ergotropic structures in the heart rhythm regulation.

The expression of markers associated with epithelial-mesenchymal transition (EMT) and extracellular matrix degradation in human uveal melanoma tissue samples and postequatorial zone of the choroid was assessed by immunohistochemical staining. Increased expression of EMT markers E-cadherin and vimentin was observed in the tumor. The ratio of MMP-9 to TIMP-1 proteins related to the extracellular matrix degradation was higher in the tumor. These results may indicate activation of EMT-like process in the uveal melanoma cells and degradation of the extracellular matrix, which can contribute to the development of collective invasion in uveal melanoma.

To study the para- and transcellular permeability of columnar epithelium and follicle-associated epithelium of Peyer's patches in the rat intestine, LPS was applied from the mucosal side to simulate the action of endotoxins from gram-negative bacteria of gut microbiota. LPS did not affect transepithelial resistance or sodium fluorescein permeability, but increased the levels of claudin-3 and claudin-4 in enterocytes, suggesting strengthening of the paracellular intestinal barrier. Transcellular permeability was evaluated by electron microscopy based on the number of vesicular structures in the cytoplasm of different cell types. LPS increased the number of small vesicles in follicle-associated epithelium of Peyers' patches. In columnar epithelial cells, LPS reduced the number of smaller vesicles and increased the number of larger ones. LPS did not damage the tissue barrier, but enhanced transcytosis, which could potentiate the effects of endotoxin on its receptors in the intestinal mucosa.

The concentrations of nitric oxide (NO) donors in the plasma of pregnant women with preeclampsia is several times higher than in healthy pregnant women. Antihypertensive drugs acting not through the NO-mediated mechanisms normalized BP in some women with preeclampsia, but did not significantly reduce the levels of NO donors in the plasma. It appears that preeclampsia is associated with insufficient NO availability for the targets, rather than low intensity of NO synthesis. The concentration of NO donor molecules in the plasma can therefore be a useful additional diagnostic marker of preeclampsia.