Vol 28, No 3 (2024): PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY

Relevance. The use of radiation therapy in the treatment of malignant neoplasms actualizes the study of ways to protect healthy tissues from radiation damage. Due to the small number of studies aimed at studying structural and functional changes of kidneys both at their direct irradiation with electrons and at radiotherapy of adjacent organs, it is necessary to carry out complex research. One of the promising directions of radiation nephropathy treatment is the use of antioxidant preparations, in particular ascorbic acid. Aim. Morphofunctional evaluation of the kidney after local electron irradiation and ascorbic acid administration. Materials and Methods. Wistar rats (n=90) were divided into groups: I — control (n=15); II — irradiation, 2 Gy dose (n=15); III — irradiation, 8 Gy dose (n=15); IV — irradiation, 2 Gy dose + ascorbic acid (intraperitoneal injection; dose 50 mg/kg) (n=15); V — irradiation, 8 Gy dose + ascorbic acid (intraperitoneal injection; dose 50 mg/kg) (n=15); VI — ascorbic acid (intraperitoneal injection; dose 50 mg/kg) (n=15). Kidney slides were stained with hematoxylin and eosin. In addition, blood biochemical examination was performed for creatinine, urea nitrogen, C-reactive protein, cystatin C to creatinine ratio was calculated, and kidney homogenate for malonic dialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) concentration levels. Results and Discussion. It was found that pre-radiation administration of ascorbic acid (intraperitoneal injection; dose 50 mg/kg) in the model of acute radiation nephropathy induced by local irradiation with electrons at doses of 2 Gy and 8 Gy contributed to a pronounced reduction of pathomorphologic and biochemical changes. Conclusion. Local irradiation with electrons at doses of 2 Gy and 8 Gy leads to the development of radiation nephropathy. At the same time, pre-irradiation administration of ascorbic acid reduces the strength of radiation-­induced kidney damage, as well as enhances the efficiency of antioxidant defense.

Relevance. The search for new methods of effective therapy for traumatic brain injury is one of the important tasks of modern biomedicine. One promising approach for treating traumatic brain injury is cell therapy. The aim of the work is to study the therapeutic effect of glial progenitor cells derived from induced pluripotent stromal cells in an experimental model of traumatic brain injury. Materials and Methods. Modeling of traumatic brain injury was carried out on mature male Wistar rats. The therapeutic group was administered a single dose of 750*10³ cells/ml glial progenitor cells with a volume of 1 ml, and the control group — 1 ml of phosphate-­buffered saline. Administration was carried out intra-­arterially 24 hours after injury. To analyze the therapeutic effectiveness, an MRI study was performed on the 14th day, as well as a limb-placing test on the 1st, 3rd, 7th and 14th days. Histological examination was carried out on days 1, 3 and 7 after administration to assess the migration and distribution of stained cells (concentration 750*10³ cells/ml) by lipophilic dye PKH26 (Sigma, USA) at the rat’s brain tissues after traumatic brain injury. Measurements of injury volume and counts of PKH26-stained cells were performed using ImageJ software (Wayne Rasband, National Institute of Mental Health, Bethesda, MD, USA). The statistical analysis was carried out using GraphPad Prism 8.2.0 program (GraphPad Software, Inc., USA). Results and Discussion. Administration of GPCs led to decreasing the damage volume. Significant decrease in sensorimotor deficit was observed on days 3, 7 and 14 after injury compared with the control group. Intra-arterial administration resulted in successful delivery of glial progenitor cells to brain tissue. Cells were detected in the cerebral cortex, hippocampus, and striatum on day 1, and were not observed on days 3 and 7 after administration. Conclusion. Intra-arterial administration of GPCs leads to efficient migration of cells into brain tissue. Glial progenitor cells therapy promotes neurorecovery processes after traumatic brain injury. This therapy is a promising treatment for traumatic brain injury.

Relevance. Aging is a natural biological process of a retrograde nature, during which there is an imbalance of all systems, including the matrix metalloproteinase (MMP) system and tissue inhibitors of matrix metalloproteinases (TIMP). And vascular aging is associated with functional and structural changes primarily in the arterial vasculature with age. Aging may be a trigger factor for pathological changes in the endothelium. The molecular mechanisms underlying the process of vascular endothelial dysfunction include increased expression and activation of matrix metalloproteinases, the concentration of which changes with aging. Numerous studies report the role of MMP-1, –2, –9, –12 in the pathogenesis of premature aging of the endothelium; they initiate cell apoptosis, which contributes to increased permeability, but there are no studies in which all age categories of both men and women were analyzed, not burdened by somatic pathology. This study examines the features of the proteolysis/antiproteolysis system in apparently healthy people of different ages and genders. Materials and Methods. As part of the pilot study, 347 apparently healthy people took part (226 women and 121 men, divided by age, according to the WHO classification), who underwent the first stage of clinical examination at the State Budgetary Institution “Consultative and Diagnostic Center of the Mountains. Yuzhno-­Sakhalinsk”, in which the level of MMP and TIMP in the blood serum was determined by solid-­phase ELISA, ng/ml. Statistical processing of the research results was carried out using the IBM SPSS Statistics Version 25.0 software package. Results and Discussion. Changes in the proteolysis/antiproteolysis system were determined in both a group of men and women of different ages, which can be characterized as not pathological, but close to such. It was found that in men aged 60-74 years, discoordinated work of matrix metalloproteinases and their inhibitors was recorded in the direction of enhancing the profibrosing effect, and in women in the same age category, the exact opposite component was identified — anti-fibrosing. Conclusion. The current development has demonstrated the influence of age and genetic resources on the system of matrix metalloproteinases and their tissue inhibitors, in addition, a special age group has been identified — the elderly group, which requires protection of the vascular system in order to monitor the impaired proteolysis/antiproteolysis system.

Relevance. Despite significant improvement, the epidemiological situation regarding tuberculosis in Russian prisons remains not entirely favorable. It is advisable to assess the epidemiological situation regarding penitentiary tuberculosis in Russia in the post-pandemic period and against the backdrop of a special military operation. Aim: to assess the dynamics of the development of the tuberculosis epidemic situation and the state of provision of TB care in prisons of the Russian Federation in 2023. Scientific novelty: for the first time, a study of the epidemic situation of penitentiary tuberculosis was carried out in the context of a special military operation and in the period following the COVID-19 pandemic. Materials and Methods. Data from official (federal and departmental) statistical observation for 2000-2023 was studied. Results and Discussion. In 2023, there is an acceleration in the rate of decline in the incidence of tuberculosis in pre-trial detention centers to 15.8% (p<0.001), while maintaining a stable rate of decline in correctional institutions. In general, in penitentiary institutions, the incidence of tuberculosis decreased from 580,4 in 2022 to 540,0 per 100,000 in 2023. The share of new cases of tuberculosis detected in penitentiary institutions among all new cases of tuberculosis decreased from 6.49% in 2022 to 5.63% in 2023. Mortality from tuberculosis changed statistically insignificantly (from 5.8 in 2022 to 4.5 per 100,000 in 2023; p=0.5). The prevalence of tuberculosis fell to 1982.3 per 100,000. The proportion of patients with tuberculosis combined with HIV in 2023 was 36.4%. Conclusion. The special military operation and the COVID-19 pandemic did not have a negative impact on the epidemiological situation of tuberculosis in Russian prisons. There may be some positive impact of the special military operation on the epidemic situation regarding tuberculosis, associated with the involvement of socially vulnerable sections of the population in economic and defense activities, which resulted in an increase in their standard of living and a decrease in the incidence of tuberculosis, which manifested itself in a decrease in the incidence of tuberculosis in pre-trial detention centers to a historical minimum.

Relevance. The recent increase in inflammatory, allergic and infectious diseases needs to update new ways of raising non-specific resistance of the organism. Innate immunity provides the first line of defense against pathogens through the activation of receptors that detect microorganisms: TLRs, NLRs and CLRs. Muramyl peptides that form the cell wall of all known bacteria are recognized by NLRs and trigger immune responses to eliminate pathogens. The aim of this study was to investigate the effect of muramyl peptides on the production of chemokines, growth factors, pro-inflammatory and anti-inflammatory cytokines by human mononuclear cells. Materials and Methods. Mononuclear cells were isolated from the peripheral blood of healthy volunteers using the Cell Separation Media Lympholyte CL 5015 reagent and cultured for 4 hours in the presence of glucosaminyl muramyl dipeptides GMDP, GMDP-OH, GMDP-Lys, GMDP-LL; an adequate amount of medium was added to the control wells. The levels of chemokines, growth factors, proinflammatory and anti-inflammatory cytokines were measured using magnetic beads with antibodies according to the manufacturer’s instructions Luminex 200, Merck (Millipore) equipment, and software (Burlington, Massachusetts, USA). Results and Discussion. It was found that muramyl peptides GMDP, GMDP-ON and GMDP-Lys enhance the production of cytokines IL-1a, IL-1b, IL-1RA, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12P40, IL-12P70, IL-15, MDC, sCD40L, IFNα2, IFN-γ, TNF-a, TNF-β, GM-CSF. GMDP-LL does not affect the production of cytokines. At the same time, muramyl peptides with the L-configuration of alanine and the D-configuration of isoglutamine (L-D muramyl peptides) did not change the values of IL-2, IL-3, IL-5, IL-9. Conclusion. The D-configuration of isoglutamine is fundamental for the implementation of the regulatory activity of muramyl peptides. A wide range of bacterial bioregulators, the source of which are microorganisms, regulate the host homeostasis and trigger immune reactions, which, depending on the context, can have opposite effects. L-D muramyl peptides activate mononuclear cells, which begin to produce proinflammatory cytokines and chemokines, as well as growth factors necessary for the destruction of pathogens. In addition, anti-inflammatory cytokines are also triggered, which have a regulatory role in the appearance of memory cells and the weakening of inflammatory reactions. Thus, normally, muramyl peptides participate in maintaining tolerance to microflora and maintaining immune homeostasis.

Relevance. Infantile hemangiomas are the most prevalent vascular tumors in children. Since the natural progression of infantile hemangiomas is typically benign, over 90 % of cases do not require medical intervention. However, treatment is necessary for infantile hemangiomas that present local complications, functional impairments, or a risk of disfigurement. In this article we presented two children with mixed and deep infantile hemangiomas, with satisfactory therapeutic responses after treatment with topical timolol maleate. Conclusion. Timolol maleate is an effective, well-tolerated, and safe treatment option for various types of infantile hemangiomas.

Relevance. A key factor influencing the effectiveness of assisted reproductive technology programmes is the quality of the embryo transferred into the uterine cavity. The aim is to investigate the possibility of using quantitative assessment of genomic (gDNA), mitochondrial DNA (mtDNA) levels in spent culture medium (SCM) and mtDNA in the trophectoderm (TE) as a marker of successful implantation and pregnancy lasting more than 12 weeks. Materials and Methods. The study included 195 SCM samples from 93 couples with infertility. Frozen embryo transfer (FET) was performed in 43 patients. The level of gDNA, mtDNA in SCM by real-time PCR and mtDNA in TE by NGS was analysed depending on the chromosomal status of embryos and the outcome of FET. Statistical analyses were performed in Jamovi software. Results and Discussion. Depending on the outcome of transfer, the patients were divided into groups: Group 1 — negative result, n=18; Group 2 — pregnancy continuing for more than 12 weeks, n=25. mtDNA and gDNA in SCM were statistically significantly lower in group 2 compared to group 1 (p=0.007 and p=0.01, respectively). When mtDNA levels in SCM were <95 copies, the odds of pregnancy rate and ongoing pregnancy were increased 3.2-fold (95 % CI=1.1–31.6). Prediction formulas for the probability of ongoing pregnancy after FET were proposed for continuous (sensitivity was 67.0 %, specificity was 91 %, area under the curve (AUC) was 90.0 %) and binary (sensitivity was 75.0 %, specificity was 70 %, AUC was 83.8 %). Thus, the level of gDNA and mtDNA copy number in the embryo culture medium is a significant prognostic factor for the onset and prolongation of pregnancy in ART programmes. Depending on the ploidy of the blastocysts, we analysed the level of mtDNA in TE, gDNA and mtDNA in the SCM of embryos in groups 1.1. (euploid, n=98) and 2.1. (aneuploid, n=97). No differences were detected in the compared groups. Conclusion. Assessment of gDNA and mtDNA levels in SCM may be an additional non-invasive marker for selection of the most promising euploid embryo for transfer into the uterine cavity.