Том 109, № 5 (2023)

Natural killer cells (NK) and T-lymphocytes with NK functions (NKT) are the leading effectors of the mother’s immune tolerance to a semi-allogeneic fetus and have a fetal trophic effect during physiological pregnancy. Tim-3 (T-cell Ig and mucin domain-containing protein 3) and CD9 molecules play a critical role in the immunoregulatory and fetal trophic functions of NK and NKT, but their expression in peripheral blood cells has not been studied. The aim of this work was to study the expression of Tim-3 and CD9 in peripheral blood NK and NKT during physiological pregnancy. The object of the study was the peripheral blood of healthy women in I and III trimesters of a physiological pregnancy. The control group consisted of healthy non-pregnant women in the first phase of the menstrual cycle. Expression of Tim-3, CD9 molecules was analyzed by flow cytometry on regulatory NK (CD16^–CD56^bright) and NKT (CD16^–CD56⁺), cytotoxic NK (CD16⁺CD56^dim/–) and NKT (CD16⁺CD56⁺). It was found that in the first trimester of pregnancy, the total number and subpopulation composition of NK and NKT cells did not change. Tim-3 expression increased in all NK and NKT subpopulations, except for cytotoxic CD16⁺CD56^dimNK. CD9 expression increased in all NK subpopulations, but in NKT did not differ from non-pregnant. At the same time, a direct correlation between CD9 and Tim-3 expressions was revealed in regulatory NK and NKT in the first trimester of pregnancy. In the third trimester, the regulatory CD16^–CD56^brightNK number increased, while cytotoxic CD16⁺CD56^dimNK and regulatory CD16^–CD56⁺NKT decreased compared to non-pregnant women. The number of CD16⁺CD56^–NK did not change in I and III trimesters of a physiological pregnancy. Tim-3 expression was upregulated in all NK and cytotoxic NKT subpopulations, while CD9 was upregulated only in regulatory NKs. Thus, Tim-3 and CD9 molecule expressions of s on different NK and NKT subpopulations changed during I and III trimesters of a physiological pregnancy, which plays an important role in the regulation of their phenotype and functions.

This study presents a comparison of the effect on EEG electrical activity in the range of infraslow frequencies of two methods: infra-low frequency EEG biofeedback and heart rate variability training. The study involved 17 healthy subjects aged 21 to 50 years with minor symptoms of a physiological or psychological nature, who did not have a history of neurological or psychiatric diseases. To evaluate the results of the training, we analyzed the spectral power of slow EEG oscillations during the performance of the attention test (Visual Go/NoGo), recorded before and after twenty sessions of biofeedback. Both the subjective assessment of the physiological and psychological state and the results of the visual test showed more pronounced positive changes under the influence of EEG biofeedback compared to the cases of heart rate variability training. A significant increase in the amplitudes of oscillations in the infraslow EEG range was observed only after EEG biofeedback.

This study aims to examine the efficiency of intravenous transplantation of human mesenchymal stem cells (hMSCs) performed 7 days after cerebral ischemia/reperfusion (I/R) for recovery of the functional activity of K_ATP-channels of cerebral arteries. Using a device for intravital visualization of pial vessels, the reaction of arteries to the K_ATP-channel blocker glibenclamide (GB), the activator of the same channels of pinacidil (PI), acetylcholine (ACh), and ACh against a background of GB action (ACh/GB) 14 and 21 days after I/R and intravenous hMSC transplantation performed 7 days after ischemic exposure. On exposure to GB 14 days after I/R, 1.5–1.8 times fewer arteries narrowed than in the sham–operated (SO) rats. By day 21 after I/R, the constriction reaction was completely restored, except for arteries with a diameter more 40 μm. In the cell–therapy group, the constrictor response to GB was completely recovered to the level of SO animals in arteries with a diameter less than 40 μm by 14 day after I/R exposure; in arteries with a diameter of more than 40 μm, the constriction reaction did not recover until 21 days. The number of dilations per ACh/GB compared to a clear ACh in SO rats was reduced in 1.6–1.8 times on 14 day after I/R and in 1.6–6.6 after 21 days. In I/R animals on 14 day, the number of dilatations per ACh/GB compared to clear ACh was significantly increased in arteries with a diameter of more than 20 μm by 1.5–1.7 times, and after 21 days in arteries with a diameter of more than 40 μm by 1.2 times. After the introduction of hMSC, GB blocked ACh–mediated dilation in arteries less than 40 μm in diameter both on days 14 and 21 after I/R. In arteries with a diameter of more than 40 μm the functional activity of K_ATP-channels did not recover until 21 days. Conclusion. I/R of the rat cerebral cortex reduces the contribution of K_ATP-channels to maintaining the basal tone of the pial arteries and almost completely excludes these channels from the formation of ACh–mediated dilation during 21 days of the postischemic period. Practically did not participate in the dilatory response. Intravenous transplantation of hMSC, performed 7 days after I/R, results in restoration of participation of SMC K_ATP-channels in maintaining the basal tone and ACh–mediated dilatation of pial arteries with a diameter less than 40 μm already 14 days after I/R.

Changes in the gut microbiome are recognized as an important component of obesity in both adults and children. One factor in the gut microbiome formation is the infant feeding type, which may also have a prolonged effect on the microbial community. Breast milk contributes to the formation of mucosal tolerance to the intestinal microbiota. In turn, trefoil factors (TFF2 and TFF3) are important components of the mucosal barrier. The aim was to study the composition of the gut microbiota and the trefoil factors level in the blood of children and adolescents with obesity, depending on the infant feeding type. The study included 93 non-obese children (Group 1) and 92 obese children (Group 2). Serum TFF2 and TFF3 levels were determined by enzyme immunoassay in each study participant. The taxonomic composition of the fecal microbiome was determined by metagenomic sequencing of the 16S rRNA gene. In general, the taxonomic composition of the gut microbiota in Groups 1 and 2 was similar. However, Group 2 had less by [Prevotella], Epulopiscium and Haemophilus and more by Clostridium and Catenibacterium. Neither obesity nor the infant feeding type of influenced the serum concentration of TFF2 and TFF3. However, the infant feeding has a prolonged effect on the gut microbiota, and in Group 2 this effect was less pronounced. In Group 1, breastfeeding led to the formation of a complete mucosal tolerance to the microbiome, which did not occur with mixed and bottle feeding. In Group 2, most of the “TFFs–gut microbiome” associations were positive, indicating an unfavorable interaction between intestinal wall and microbiome in obese children and adolescents. Thus, infant feeding type seems to be a weak but significant factor in the gut microbiome formation in children and adolescents, which also affects the formation of mucosal tolerance to the intestinal microbiota.

Adipokine leptin plays an important role in the regulation of the reproductive system. It stimulates the activity of the hypothalamic-pituitary-gonadal axis by indirectly acting on GnRH-secreting neurons and modulates testicular steroidogenic function by binding to leptin receptors in Leydig cells. A leptin fragment 116–122 (LF) including the main receptor-binding determinants of this adipokine, normalizes metabolic parameters in animals with diet-induced obesity. However, its ability to influence the steroidogenic function of the testes, including through interaction with GnRH neurons of the hypothalamus, has not been studied. The aim of this work was to study the effects of a single and three-day intranasal administration of LF (200 μg/rat) on the blood testosterone level and the expression of steroidogenic genes in the testes in mature male Wistar rats. To evaluate the effect of LF on testicular steroidogenesis upon stimulation with human chorionic gonadotropin (hCG, 15 IU/rat, s/c), a stimulator of testosterone synthesis and an antagonist of the GnRH receptor cetrorelix (75 μg/kg, s.c.) an inhibitor of testicular steroidogenesis. It has been shown that LF increases the level of testosterone in the blood after a single injection, and after a three-day administration it enhances the steroidogenic effect of hCG. LF and hCG increased the expression of the Star gene encoding the key regulatory protein of steroidogenesis StAR. Administration of cetrorelix reduced testosterone levels and Star expression, and compensatory increased expression of the luteinizing hormone receptor gene. The potentiating effect of LF on hCG-induced stimulation of testosterone levels and Star expression was not detected under conditions of GnRH antagonist treatment. Thus, LF is capable of stimulating steroidogenesis in rat testis by itself and potentiating the steroidogenic effects of hCG. Since its effects are suppressed in the presence of a GnRH antagonist, there is reason to assume that the effect of LF is realized through stimulation of hypothalamic GnRH neurons.