Bulletin of Experimental Biology and Medicine最新文献

Sex differences in the development of toxic liver cirrhosis in 12-month-old Wistar rats and the specific features of liver cirrhosis therapy with bovhyaluronidase azoximer were studied. The severity of pathological changes assessed by ultrasound, histological, biochemical, and hematological methods in male rats with liver cirrhosis exceeded that in female rats. The studied drug demonstrated anti-inflammatory and antifibrotic activity in aged rats with toxic liver cirrhosis, and its effect did not depend on the sex. Sex-related mechanisms may underlie the positive changes on liver cirrhosis under the influence of the test drug.

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.

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.

Lantibiotics warnerin and hominin isolated from growth media of Staphylococcus warneri DSMZ 16081 and S. hominis GISK 284, respectively, have pronounced immunomodulatory effects. Both peptides significantly modulated the microbicidal potential of leukocytes; the effect depended on the concentration and presence of the inducer. Warnerin inhibited ROS in high concentrations and stimulated ROS production in low concentrations in both spontaneous and stimulated samples. Hominin, on the contrary, enhanced spontaneous ROS production, but inhibited stimulated ROS production. Both peptides decreased the phagocytic activity of monocytes and neutrophils and activated the spontaneous production of both pro- (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines. Comparison of the two peptides revealed that hominin showed higher immunomodulatory activity.

We studied cytotoxicity and the effect on cell viability in in vitro incubated mammalian embryonic cells of purine derivative aminophylline, indole derivative ergotamine tartrate, as well as the phosphoric acid derivatives 3-ethyl-2-hydroxy-2-oxa-1,4,2-oxazaphosphorinane (EHOOP) and α-ethyl-α-N-(hydroxyethylamino)methylphosphonic acid (ENHEAMPA) after inoculation of the cells with vaccine avipoxviral strain FK (fowl) with initial infectious titer 10⁶ CCID₅₀/ml for 24 or 48 h. The tested substances were applied for 24 or 48 h at concentrations of 10^-11-10^-2 mol/ml (aminophylline and ergotamine tartrate), as well as at 10^-11-10^-3 mol/ml (EHOOP and ENHEAMPA). In cell suspensions, the cytotoxic concentrations CC₅₀ (mol/ml) were determined corresponding to the death or alterations in half of the cells. They were 10^-3 and 10^-2 mol/ml for purine and indole analogues, respectively, whereas similar values for two phosphoric acid derivatives were 10^-5-10^-4 mol/ml. At low concentrations of the test substances, a decrease in cell viability was observed when exposure was prolonged from 24 to 48 h, which can be explained by pathogenic action of the inoculated virus. A decrease in cell viability was also observed when the concentration of the test agents was elevated, which can be explained by their intrinsic cytotoxic action at high concentrations. Overall, purine and indole analogues were less toxic for cultured mammalian cells than the test phosphoric acid derivatives. Purine analogue aminophylline had the lowest cytotoxicity, but exhibited maximum antiviral activity.

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.