Bulletin of Experimental Biology and Medicine最新文献

The study of the newly synthesized 4,10-di(ethoxyacetyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,0,03,11,05,9]dodecane (from the class of hexaazaisovyurcitanes) has revealed that the compound when administered intragastrically and intraperitoneally exhibits high antinociceptive efficacy in tests of nociception of different genesis (chemogenic, thermal, mixed) comparable and/or superior to the effect of Tramadol.

Metabolic profiling of the blood, plasma, and erythrocyte mass in patients with type 2 diabetes mellitus was performed using HPLC. When analyzing the spectra of supernatants obtained from plasma and whole blood, potential biomarkers of type 2 diabetes mellitus with a mass charge number of 314.45, 397.45, and 702.55 atomic mass units were identified. Identification of the molecules requires further investigation.

Recombinant modified vaccinia virus Ankara (rMVA) viruses expressing two forms of SARS-CoV-2 receptor-binding domain (RBD) of S protein fused to viral N protein were constructed and the immunogenicity of these rMVA was evaluated in BALB/c mice. Vaccination of animals with these vaccine vectors led to the production of SARS-CoV-2 neutralizing antibodies and induced a T-cell response targeting both RBD and N proteins.

We studied the effects of glucose and glutamine deficiency on the survival of astrocytes after ischemic injury and examined the mechanisms of cell death. It was found that glutamine can serve as an alternative energy substrate that maintains oxidative phosphorylation and glycolysis in astrocytes. However, the combination of glucose and glutamine reduced the ischemia-induced increase in intracellular calcium and the expression of proapoptotic proteins to a greater extent. The results of the study indicate the possibility of using glutamine to maintain the viability of brain cells under conditions of oxygen and energy substrate deprivation.

We studied the effect of melatonin in the original rectal suppositories on neurological status, microcirculation, and morphology of focal ischemic infarction in experimental acute cerebral ischemia modeled using the Chen technique (simultaneous diathermocoagulation of cerebral pial vessels in the posterior parts of the left frontal lobe and the anterior parts of the left parietal lobe). The animals of the experimental groups were administered either original rectal suppositories weighing 100 mg containing 2.5 mg of melatonin or a citicoline solution of 100 mg/kg intraperitoneally for 7 days. The neurological status was the Garcia and limb-placing test scores, microcirculation, and morphological parameters of the lesion on days 3 and 7. The use of original rectal suppositories reduced neurological deficits, increased the Garcia and limb-placing test scores, decreased the area of focal ischemic infarction, number of chromatolysis neurons, shadow cells, and an increase in the number of intact neurons and small vessels. The effects of original rectal suppositories with melatonin were significantly more pronounced than the effects of citicoline solution. The positive effect of melatonin in experimental acute cerebral ischemia was determined by its angiogenetic (formation of new blood vessels) and reparative (recovery of damaged neurons) effects.

Markers of α2- and β1-adrenergic receptors (AR) were detected immunohistochemically in the liver of db/db mice with obesity and type 2 diabetes mellitus before and after melatonin treatment. Melatonin (1 mg/kg in 200 μl distilled water) was administered intragastrically from the 8th to the 16th week of life. The comparison groups were intact and placebo-treated db/db mice. Melatonin administration resulted in a significant increase in the relative areas of β1- and α2-AR expression, with a tendency towards an increase in the area ratio, as well as a significant increase in the ratio of β1/α2-AR concentrations due to preferential increase in β1-AR parameters. Melatonin administration apparently reduces sympathetic neuropathy of the liver and promotes the shift of lipid metabolism processes in hepatocytes towards lipolysis activation, which allows us to consider this hormone as a promising component of complex therapy of fatty liver disease.

Sex differences were studied under normal conditions and after a single mild stress in inbred Wistar rats. It was found that intact females had higher blood corticosterone and leptin levels than males. In females, locomotor activity and the number of active defense reactions in elevated plus maze were higher, while the number of passive defense reactions was lower than in males. After stress, the blood corticosterone and leptin levels increased in both females and males, while the level of the main sex hormones decreased. We found for the first time that leptin and corticosterone levels positively correlated with anxiety index, locomotor activity, and number of active defense reactions and negatively correlated with testosterone and estradiol levels. A hypothesis was put forward that leptin, together with corticosterone, is involved in the organization of the adaptive behavior under stress conditions.

Metagenomics of bacterial communities in tuberculosis caseous necrotic mass indicates the predominance of facultative anaerobes. Nine strains isolated from the tuberculosis necrosis were identified to species and whole-genome sequencing was performed: Staphylococcus hominis (3 strains), S. epidermidis (3 strains), Corynebacterium ureicelerivorans (2 strains), and C. kefirresidentii (1 strain). Prediction of metabolic pathways and virulence factors showed that Corynebacterium and Staphylococcus possess gene sets that are absent in Mycobacterium tuberculosis: lipases and proteases for the degradation of caseous necrosis, glutamate and polysaccharide capsules, ureases capable of increasing pH of the caseum; and Fe(III) uptake systems. The isolated species can form a bacterial consortium with M. tuberculosis at the early (Corynebacterium) and later (Staphylococcus) stages of necrotization of the tuberculosis focus in the lungs.

We studied the effects of Semax on spontaneous fluctuations of intracellular calcium ion concentration [Ca²⁺]_i in pyramidal neurons on hippocampal slices and on proton-induced increase in [Ca²⁺]_i in cerebellar granule cells in cerebellar slices. Application of Semax (1 μM), significantly increased the frequency of spontaneous [Ca²⁺]_i fluctuations in the pyramidal layer cells of the hippocampal CA1 field, but had no significant effect on proton-stimulated increase in [Ca²⁺]_i in cerebellar granule cells. These data provide insight into the localization of cellular targets and elucidate the dynamics of the initial stages of interaction between the peptide and the hippocampal neuronal network. The primary mechanism of the neuroprotective effect of Semax appears to be unrelated to attenuation of calcium entry through acid-sensing ion channels in cerebellar granule cells.

It was shown that blocking of glycolysis by 2-deoxy-D-glucose (DG) inhibits LPS-induced NO production in glial cell cultures and reduces the mitochondrial membrane potential. Lactate partially prevented the decrease in the mitochondrial membrane potential of gliocytes, but did not affect the inhibitory effect of DG. Immunocytochemical typing showed the presence of a large number of astrocytes and microglia in the culture. In the control, microglial cells had a large number of processes, which is typical of nonactivated cells, whereas in LPS-treated cultures, microglia had a flattened amoeboid morphology typical of activated microglia. In cultures treated with LPS against the background of DG, both cells with processes and amoeboid cells were present. Our results indicate that inhibition of glycolysis is a strong modulating factor in inflammation.