Genetic contribution of pre-Slavic populations to gene pools of modern Russia is increasingly relevant, along with genetic footprints of the Golden Horde invasion. The novel genome-wide approaches enable advanced solutions in this field. The study aimed at searching for the footprints of genetic interaction among Finnicspeaking, Slavic and Turkic-speaking populations of Central Russia and Volga Region and their reflection in pharmacogenetic landscape. Modeling ancestral components by ADMIXTURE software and their mapping involved genome-wide genotyping data for 248 individual genomes representing 47 populations of 9 ethnic groups. Of specific ancestral components identified in each of the Finnic-speaking peoples, only Mordovian ancestral components are common for all populations within the studied geographic area, regardless of their linguistic affiliation. Gene pools of Russian populations include 80% of intrinsic component, 19% contribution from Finnic-speaking peoples, and 1% of Central Asian influence. The Tatar gene pool combines all identified ancestral components, including 81% contribution from Finnic-speaking peoples and only 12% of Central Asian influence, which prevents using it as a reference for the assessment of Golden Horde footprints in Russian gene pools. A map of genetic distances from Ryazan Russians based on a panel of 42 pharmacogenetic markers reveals a landscape strikingly independent from the selectively neutral ancestral genomic patterns. For instance, populations of Mordovia, Kaluga, Smolensk, and Kostroma regions are the closest to Ryazan Russians in pharmacogenetic status, whereas populations of Ryazan and Nizhny Novgorod regions have strikingly divergent pharmacogenetic status despite the similarity of the selectively neutral ancestral genomic patterns. These findings confirm the relevance of targeted pharmacogenetic characterization for gene pools of Russia.
VIEWS 3811
Autoimmune mechanisms have been implicated in the negative effects of vaccines on female reproductive health. This study evaluates the endogenous levels of self-reactive antibodies and ovarian reserve-associated hormones before and after immunization with the domestically developed Gam-COVID-Vac combined vector vaccine to check for possible reproductive sequelae. The prospective study enrolled 120 women aged 18–49, subject to vaccination with Gam-COVID-Vac. Ovarian reserve was assessed prior to vaccination and 90 days after the first component injection. Profiles of specific antibodies to self-antigens, including phospholipids, nuclear antigens, FSH, progesterone, and also thyroid, ovarian, trophoblast, and zona pellucida antigens, were assessed at the same time points by enzyme immunoassay. Overall, the vaccination had no effect on the levels of ovarian reserve-associated hormones and autoantibodies, apart from a transient increase in positivity for antiphosphatidylethanolamine IgM and anti-dsDNA IgG. Seroprevalence of elevated serum autoantibodies constituted 70.8% before and 75% after vaccination. According to the results, immunization with Gam-COVID-Vac does not affect ovarian reserve or autoimmune status, thus being safe for the female reproductive potential.
VIEWS 3099
Severe form of COVID 19 has been linked to the phenomenon of dysregulated inflammation with excessive cytokine release and elevated interleukin 6 (IL6) levels. Suppressive agents enabling specific inhibition of cytokines, notably monoclonal antibodies to IL6 and its receptors, have been applied as a rescue therapy in COVID 19 despite the underexplored clinical scope for these biologic medications. This study aimed to evaluate the clinical utility of IL6 receptor antagonist tocilizumab in moderate symptomatic COVID 19 prone to aggravation. The retrospective cohort study enrolled two groups of hospitalized patients (a total of n = 72) diagnosed with moderate COVID-19. The main group received a single 400 mg dose of tocilizumab (TCZ) on top of standard therapy. The comparative analysis included statistical evaluation for a number of clinical and laboratory parameters at reference time points and disease outcomes with regard to treatment strategy. Overall, TCZ administration provided no advantages in terms of oxygen supplementation status, disease progression, or survival. Lethal cases constituted 19.2% (10 pts) and 5% (1 pt) in TCZ and comparison groups, respectively. The results indicate that administration of monoclonal antibody drugs in hospital patients with COVID-19 must follow differential schemes with regard to the disease severity and comorbidities, as well as proper commencement schedules.
VIEWS 2851
Skin wound healing mechanisms and new ways of improving their efficiency represent an important focus in medicine. In this regard, regulatory peptides, which exhibit physiological polyfunctionality and modulate cell growth and differentiation, are of special interest. This study evaluates the effects of Gly-His-Lys (GHK) and Gly-His-Lys-D-Ala (GHK-D-Ala) peptides in the infected skin wound healing. The wounds were modeled in rats (n=150) by full-thickness dorsal skin defects. The peptides were administered intracutaneously at daily doses of 0.5 or 1.5 µg/kg. The healing was assessed on days 3, 7, and 10 by histomorphometric examination of the wounds with adjacent intact skin. GHK-D-Ala administered at daily doses of 0.5 µg/kg had pronounced positive effect on regeneration processes in the wound, as indicated by significantly reduced numbers of granulocytes and lymphocytes with increased representation of fibroblastic lineages and macrophages, and the resulting higher cellular index (p < 0.05–0.001). At higher doses of GHK-D-Ala (1.5 µg/kg), the beneficial effects were less pronounced. According to the comparative morphological examination, the highest positive effect was achieved with 0.5 µg/kg of GHK-D-Ala. Thus, local administration of the GHK peptide with extra D-alanine at carboxy-terminus significantly mitigated the inflammatory reaction and facilitated the healing of infected skin wounds in rat model.
VIEWS 3156
Simultaneous pancreas and kidney transplantation (SPK) provides effective treatment in patients with type 1 diabetes mellitus (T1DM) and end-stage renal failure (ESRF), mitigating the hyperglycemia and uremic syndrome. The study aimed at the assessment of morphofunctional status of the macula and macular hemodynamics in patients with T1DM after SPK. The study enrolled 45 patients subdivided into three groups: Group A — patients with T1DM after SPK; Group B — patients with T1DM and ESRF, maintained on programmed hemodialysis (PH), on waiting list for SPK; and Group C — individuals without ophthalmic or systemic pathologies. All patients were subject to the standard ophthalmological examination complemented by measurements of the central retinal thickness (CRT) and the average perfusion density (PD) in four vascular layers: superficial capillary plexus of the retina (SCP), deep capillary plexus of the retina (DCP), choriocapillaris, and choroid. The patients after SPK had significantly lower CRT (241 ± 33 µm in Group A, 309±10 µm in Group B; p < 0.05) and significantly higher PD of the macular region in both the retina (Group A: SCP — 19.0 ± 1.6%, DCP — 10.7 ± 1.3%; Group B: SCP — 11.7 ± 0.8%, DCP — 4.8 ± 0.8%; p < 0.05) and the choroid (Group A: choriocapillaris — 28.1 ± 1.8%, choroid — 31.3 ± 1.6%; Group B: choriocapillaris — 20.4 ± 1.6%, choroid — 21.8 ± 1.3%; p < 0.05), as well as significantly higher visual acuity (Group A: 0.7 ± 0.1; Group B: 0.5 ± 0.1; p < 0.05) and macular light threshold (Group A: 25.9 ± 1.4 dB; Group B: 22.3 ± 1.1 dB; p < 0.05) compared with the patients on PH. Thus, the normalization of carbohydrate metabolism and the mitigation of uremic syndrome in patients with T1DM and ESRF after SPK favorably affect the functional condition of the macular area, as indicated by the improvement in macular blood flow and visual functions.
VIEWS 2798
Alterations in intracellular signaling pathways affecting immune cell activation, proliferation and differentiation of keratinocytes in psoriasis could explain the complex pathogenesis of the disease. NF-κB is one of the intracellular signaling pathways, which is involved in regulation of numerous pro-inflammatory genes, and affects the synthesis of pro-inflammatory cytokines directly involved in the development of psoriasis. The study was aimed to assess the number of cells with NF-κB translocation in lymphocyte populations of children with psoriasis depending in the disease severity and therapy. A total of 130 children with psoriasis vulgaris were examined. The comparison group included 30 healthy children. The study was conducted using the imaging flow cytometry Amnis ImageStreamX system. It was found that there were significant differences in the number of cells with NF-κB translocation in the lymphocyte populations of both children with psoriasis and comparison group. Children with psoriasis had a higher number of cells with NF-κB translocation in the populations of T helper cells, Tact, Treg, and Th17 compared to healthy children (p < 0.05). The number of cells with NF-κB translocation in children with psoriasis correlated with the disease severity PASI (Rmul = 0.32) and BSA (Rmul = 0.31) scores, as well as with the disease duration (p < 0.05). NF-κB determination could be considered an additional criterion for the disease severity assessment in children with psoriasis. The differences in the degree of reduction of the number of cells with NF-κB translocation 24 h after administration of biologics (adalimumab, etanercept, ustekinumab) have been shown. Studying NF-κB in cell populations offers the prospect of understanding pathogenetic mechanisms of inflammation and developing new therapeutic methods for psoriasis.
VIEWS 3081
Optimization of the educational process, including distance learning, requires orderly arrangement of the information presented, which translates into the need to factor in oculomotor reactions accompanying the search for solutions to simple cognitive tasks. This need supports the relevance of the present study, which aimed to investigate the age-dependent parameters of the oculomotor reactions occurring in solving a simple cognitive task. The sample included 97 persons, 47 males and 50 females, ages 21 to 36. For the purpose of rating the oculomotor reactions, the sample was divided into age groups: 21–26 years (n = 34); 27–32 years (n = 29); 33–36 years (n = 34). The methodology that governed the rating procedures was developed by the authors of the study and relied on the Tobii EyeX eye tracking hardware and software solution (GazeControl software). The study revealed a significant correlation between orientation of the image (presentation angle) and distribution of the visual fixations: regardless of the image presentation angle and its properties (schematic monochrome or full color image), the fixations tend to fall predominantly into the top and left parts of the image (the first quadrant). Other findings include a) a significant dependence of the capability to solve simple cognitive tasks and recognize the contents of the image on the spatial orientation of the presented stimuli, and b) the number of errors made in image contents recognition increasing with age, this dependence being significant and observed for both the schematic monochrome image (p1 = 0.014; p2 = 0.016; p3 = 0.014) and the full-color image (p1 = 0.015; p2 = 0.015; p3 = 0.017). The researchers have also identified the significant angles of rotation of the presented face images that stably caused recognition errors.
VIEWS 3061