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Vol 24, No 4 (2024)

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Analytical reviews

Role of monocytes in immunopathogenesis of infectious and inflammatory diseases: from theory to practice

Trulioff A.S., Borisov A.G., Kudriavtsev I.V., Lazanovich V.A., Savchenko A.A.

Abstract

Monocytes are circulating blood cells derived from bone marrow. They are the body’s first line of defense against pathogens and are involved in immune responses against viruses, bacteria, fungi and parasites invasion. For a long time, monocytes were considered a homogeneous group of cells, but then by means of flow cytometry development it was shown that they can be divided into three subpopulations according to surface molecules CD14 and CD16 expression: classical (CD14++CD16), proinflammatory (CD14+CD16++) and intermediate (CD14++CD16+). This review focuses on various mechanisms of an implementation of the functional activity of various monocytes subpopulations and their impairment in various viral diseases, bacterial infections and sepsis.

Medical academic journal. 2024;24(4):9-32
pages 9-32 views

Original research

The interconnectedness of the motor and nociceptive systems in the conditions of operative correction of spinal deformity

Bogatyrev M.A., Saifutdinov M.S., Shchurova E.N., Savin D.M.

Abstract

BACKGROUND: The risk of complex neurological disorders after surgical correction of spinal deformity raises the question of the need for special measures for their postoperative treatment. This requires a more detailed study of the mechanisms of interaction between the motor sensory and autonomic structures of the nervous system.

AIM: The aim of the study is to search for a simple and informative method of testing the level of balance of the states of the motor and nociceptive systems in patients with spinal deformity of various etiologies in the conditions of its surgical treatment.

MATERIALS AND METHODS: A retrospective analysis of the results of electromiographic and esthesiometric examinations of 87 patients (30 male, 57 female) aged 15.6 ± 0.6 years with spinal deformities of various etiologies was carried out.

RESULTS: The scatterograms of the paired values of the electromyogram amplitude at the maximum voluntary tension m. tibialis anterior and the heat pain perception thresholds are best approximated by a polynomial of the third degree. But the approximation is acceptable only for electromyographic patterns with an unsaturated structure in the preoperative period. The nonlinear nature of the coupling of the intensity of the electrical activity of the muscle with the heat pain perception threshold contains a significant linear component. After surgical correction of spinal deformity, the approximation quality is reduced to a state of random noise. The reason for this is: postoperative increase in nociceptive activity and the consequences of anesthetic support.

CONCLUSIONS: In patients with spinal deformity, there is a correlation between the levels of voluntary muscle activity and the settings of the nociceptive system, expressed in the values of the heat pain thresholds. The nature of the coupling is expressed in the inverse relationship between the pain threshold and the amplitude of the electromyogram at maximum arbitrary voltage. This type of dependence is quite consistent with well-known physiological phenomena. The maximum severity of this interconnectedness for unsaturated patterns of the electromyogram indicates that the condition for its manifestation is a specific regime of stem centers that regulate the posture-tonic activity of muscles in patients with axial skeleton disorders.

Medical academic journal. 2024;24(4):33-40
pages 33-40 views

Biological properties of the recombinant influenza A/H1N1pdm09 virus expressing a fragment of the Streptococcus pneumoniae surface protein

Desheva Y.A., Rekstin A.R., Mayorova I.V., Kopylova N.V., Kopteva O.S., Petrachkova D.S., Kudar P.A., Kotomina T.S., Matushkina A.S., Leontieva G.F., Kramskaya T.A., Isakova-Sivak I.N.

Abstract

BACKGROUND: Live influenza vaccine strains may serve as a promising system for the delivery of target antigens to the body because such a vaccine is administered intranasally and stimulates multiple chains of immunity against both the target pathogen and the influenza virus, a serious infection that causes significant socioeconomic damage worldwide each year.

AIM: The study was aimed to evaluate the biological properties of a recombinant live influenza vaccine strain of subtype A/H1N1pdm09 expressing a fragment of the Streptococcus pneumoniae Spr1875 surface protein.

MATERIALS AND METHODS: The A/H1N1pdm09 recombinant live influenza vaccine strain expressing a 69-amino-acid fragment of the S. pneumoniae surface protein Spr1875 as part of a chimeric hemagglutinin molecule was prepared by reverse genetics using an 8-plasmid system. The reproductive activity of the recombinant virus was studied in chicken embryos, whereas immunogenicity and protective efficiency were studied in Balb/C mice.

RESULTS: The recombinant influenza virus strain with hemagglutinin H1-Spr-69 demonstrated active reproduction in chicken embryos and retained the temperature-sensitive phenotypic trait of vaccine viruses. However, its growth in the respiratory tract of mice was limited compared with the original A/H1N1pdm09 vaccine virus. Intranasal administration of the recombinant H1-Spr strain to mice resulted in stimulation of virus-specific serum IgG antibody production comparable to that induced by the classic live influenza A/H1N1pdm09 vaccine. Furthermore, this strain induced an increase in IgG antibodies against the pneumococcal insertion Spr1875. Although the A/H1N1pdm09 variant was more effective than the chimeric H1-Spr virus in preventing weight loss in mice infected with mouse-adapted influenza A/California/07/09 (H1N1)pdm09 (H1N1)pdm09 virus, the titers of the challenge virus in the lungs of mice from both vaccine groups were significantly reduced compared with unvaccinated animals.

CONCLUSIONS: The results demonstrate the ability of the chimeric recombinant H1-Spr strain to stimulate protective immunity against influenza virus.

Medical academic journal. 2024;24(4):41-50
pages 41-50 views

Normobaric intermittent postconditioning corrects development of anxiety-depressive state in the experimental model of post-traumatic stress disorder

Zenko M.Y., Baranova K.A., Rybnikova E.A.

Abstract

BACKGROUND: Despite the rapid increase in the prevalence of post-traumatic stress disorder, there are still no effective drugs for its treatment, therefore, the development of non-drug approaches is an extremely urgent task, which this study is aimed at solving.

AIM: To estimate experimentally the therapeutic effects of hypoxic postconditioning using intermittent normobaric hypoxia in a model of post-traumatic stress disorder-like pathology in rats.

MATERIALS AND METHODS: In the rat model of post-traumatic stress disorder “stress–restress”, the effects of three postconditioning regimes were investigated: three 5-min episodes of hypoxia with 9% oxygen interspaced with 15-min intervals of normoxia (reoxygenation) per day for 3 days after pathogenic stress (hypoxia/normoxia mode); three 5-min episodes of 9% hypoxia interspaced with 3-min intervals of hyperoxia with 30% oxygen in the mixture, per day for 3 days (hypoxia/hyperoxia mode); five 5-min episodes of 12% hypoxia and 3-min 30% O2 hyperoxia per day for 9 days (hypoxia/hyperoxia mode, prolonged). Animal behavior, hypothalamic-pituitary-adrenal axis function and indices of general blood analysis were analysed.

RESULTS: All the modes of normobaric postconditioning to a greater or lesser extent had a corrective effect on the manifestation of pathological symptomatology; however, triple hypoxia/hyperoxia postconditioning was more effective than other modes in terms of the totality of protective and absence of side effects.

CONCLUSIONS: The results suggest that postconditioning using intermittent normobaric hypoxia/hyperoxia for the treatment of anxiety-depressive disorders in humans, including post-traumatic stress disorder, may be a promising approach.

Medical academic journal. 2024;24(4):51-59
pages 51-59 views

Hybrid multiepitope recombinant vaccine for protection against infection caused by group B streptococcus

Leontieva G.F., Kramskaya T.A., Koroleva I.V., Kuleshevich E.V., Duplik N.V., Suvorov A.N.

Abstract

BACKGROUND: Streptococcus agalactiae, commonly known as group B streptococcus, is an important pathogen responsible for severe and sometimes fatal invasive infections in newborns. It also poses a significant risk to older adults and those with weakened immune systems. Current preventive strategies primarily include the use of antibiotics to prevent maternal-to-fetal transmission of group B streptococcus and to treat established infections. The emergence of antibiotic-resistant strains has reduced the effectiveness of these treatments and highlighted the need for alternative preventive measures. Vaccines represent a promising complement to antibiotics, potentially providing broader and more effective protection against group B streptococcus infections.

AIM: The study aims to evaluate the immunogenic properties and protective efficacy of a newly developed chimeric recombinant protein vaccine (Su4) designed to combat group B streptococcus infections. This vaccine incorporates immunodominant epitopes from five group B streptococcus virulence factor proteins. The research investigated various vaccination methods in mice, followed by an analysis of the effectiveness of the induced immune response in providing protection against multiple forms of group B streptococcus infection.

MATERIALS AND METHODS: Female outbred mice (6–8 weeks of age) were immunized subcutaneously, intranasally, or intravaginally with a hybrid recombinant vaccine polypeptide Su4 at a dose of 20 μg with repeated administration at the same dose after 21 days. Blood samples were taken from the submandibular vein on days 20 and 40 after immunization. Immunogenicity was assessed by measuring the levels of specific IgG, IgG1, IgG2a and IgG3 using ELISA. The plates were coated with Su4 protein or recombinant peptide analogs of each of the five regions of the Su4 complex molecule, and antibody concentrations were determined using standard curves. Protective efficacy was assessed by the bacterial load in the lungs and vaginal lavages of mice infected with the group B streptococcus strain 6224 nasally or vaginally at a dose of 108 CFU/mouse. Bacterial concentrations in lung homogenates and vaginal washings were determined by plating the material on Columbia blood agar.

RESULTS: The study examined the protective effectiveness of vaccination with the polyepitope molecule Su4, consisting of linear determinants of five group B streptococcus proteins. Immunization by subcutaneous, intranasal and vaginal routes showed that the Su4 protein was immunogenic and caused the production of specific IgG. Subcutaneous immunization ensured the accumulation of the highest levels of antibodies. The immune response developed according to the Th2 type and predominantly led to the induction of IgG1 antibodies, potentially capable of opsonizing bacteria and initiating phagocytosis. Vaccination resulted in accelerated clearance of group B streptococcus from the vaginal cavity of mice following infection compared with the control group, demonstrating the protective effectiveness of the stimulated immune response in protecting against group B streptococcus infections.

CONCLUSIONS: The polyepitope chimeric recombinant protein Su4 is immunogenic via subcutaneous, intranasal, and vaginal administration, inducing a systemic IgG response specific to group B streptococcus proteins. This response enhances resistance to nasal and vaginal group B streptococcus infections, indicating that Su4 is a promising candidate for a multi-epitope vaccine against group B streptococcus.

Medical academic journal. 2024;24(4):60-73
pages 60-73 views

Ability of lactoferrin to inhibit oxidative/halogenative stress and improve wound healing in rats with experimental hyperglycemia

Sokolov A.V., Ivanov V.A., Kostevich V.A., Gorbunov N.P., Voynova I.V., Vasilyev V.B., Gusev S.A., Panasenko O.M.

Abstract

BACKGROUND: Leukocyte myeloperoxidase catalyzes the formation of HOCl, which, by oxidizing and chlorinating biomolecules, contributes to the development of oxidative/halogenative stress. The latter in hyperglycemia may interfere with wound healing in patients with diabetes mellitus complications.

AIM: Evaluation of the concentration of markers of oxidative/halogenative stress and NETosis in the blood of experimental rats with hyperglycemia, its correction with lactoferrin, as well as elucidation of the effect of this multifunctional protein on skin wound healing.

MATERIALS AND METHODS: For the experimental modeling of hyperglycemia, the animals were injected once with streptozotocin at a dosage of 43 mg/kg body weight. Blood samples were collected from the tail vein of anesthetized animals. Glucose was measured by the electrochemical method. Markers of oxidative/halogenative stress were detected by the immunoenzymatic and spectrophotometric methods.

RESULTS: It was shown that in rats with streptozotocin-induced hyperglycemia, a “prophylactic+therapeutic” supplementation of lactoferrin (at a dose of 250 mg/kg on days 5, 3, and 1 before and days 2, 4, 6, and 8 after streptozotocin injection) significantly decreased blood concentration of glucose (fasting), myeloperoxidase, chlorinated ceruloplasmin, complexes of myeloperoxidase/DNA, and also prevented the decrease in thiols (SH-groups) and the activity of erythrocyte glutathione peroxidase. Moreover, lactoferrin administered according to the above regimen to rats with experimental hyperglycemia promoted wound healing, which was manifested by a 28% decrease in the wound area compared to the control animals.

CONCLUSIONS: The results obtained indicate that lactoferrin has an ability in a hyperglycemia model in animals to reduce not only the hyperglycemia level, but also to prevent the development of oxidative/halogenative stress and NETosis, which leads to improved wound healing.

Medical academic journal. 2024;24(4):74-83
pages 74-83 views

Increased somatic polyploidization in chorion of arrested pregnancies conceived through assisted reproductive technologies

Tikhonov A.V., Krapivin M.I., Petrova L.I., Chiryaeva O.G., Pashkova E.P., Golubeva A.V., Staroverov D.A., Trusova E.D., Efimova O.A., Bespalova O.N., Pendina A.A.

Abstract

BACKGROUND: The search for markers of disorders leading to miscarriage with normal embryonic karyotype is an important clinical and diagnostic problem, especially in pregnancies conceived with assisted reproductive technologies.

AIM: Analysis of chorionic cells ploidy in naturally and assisted reproductive technologies conceived pregnancies.

MATERIALS AND METHODS: A total of 52 chorion samples were included in the study. The samples were divided into groups depending on the developmental status of pregnancy (progressing/arrested), the way of conception (natural/assisted reproductive technologies) and karyotype (normal/trisomy 16). The ploidy of chorionic cells was studied using fluorescence in situ hybridization on interphase nuclei preparations. A total of 50,657 interphase nuclei were analyzed.

RESULTS: Along with predominant diploid cells, polyploid cells were detected in all chorionic samples. Their frequency varied among samples from 0.1 to 8.22%. Polyploid cells comprised mainly tetraploid cells which were detected in all samples; triploid cells were also detected in 45 samples, and octoploid cells — in 5 samples. The highest total frequency of all polyploid cell types was found in chorion from assisted reproductive technologies-conceived arrested pregnancies, and the lowest — in chorion from progressing pregnancies. Frequency of tetraploid cells demonstrated the same pattern. Frequency of triploid cells was not associated with a developmental status of pregnancy and the way of conception. However, in chorion samples with trisomy on chromosome 16 in naturally conceived arrested pregnancies, a tendency towards a decrease in the frequency of triploid cells was noted.

CONCLUSIONS: An elevated frequency of polyploid cells in chorion may indicate placentation abnormalities, leading to miscarriage even in the absence of embryonic karyotype anomalies. Therefore, an increase in somatic polyploidization in chorion may be considered a promising diagnostic marker of disorders in the placenta formation and functioning.

Medical academic journal. 2024;24(4):84-96
pages 84-96 views

Correction of neuro-immune disorders in a model of post-viral chronic fatigue syndrome with an IL-1 receptor antagonist

Filatenkova T.A., Shanin S.N., Fomicheva E.E., Ishchenko A.M., Serebryanaya N.B.

Abstract

BACKGROUND: Chronic fatigue after a viral infection is common, and physical weakness is accompanied by cognitive impairment, leading to a decrease in the individual’s quality of life, loss of working capacity and, as a result, depression. Effective treatment methods have not yet been developed.

AIM: Therefore, the aim of this study was to identify the possibility of fatigue correction with a recombinant cytokine IL-1 receptor antagonist in an experimental model of post-viral chronic fatigue syndrome in rats.

MATERIALS AND METHODS: The work was performed on male Wistar rats; experimental chronic fatigue syndrome was induced by a single injection of polyinosinic:polycytidylic acid. We analyzed changes in behavioral reactions, the level of physical activity (degree of fatigue), changes in lactate concentration in blood and the expression of IL-1β, IL-10, INFα, 5-HTT, TLR3 genes in hypothalamus, and also assessed the splenocytes cytotoxic and proliferative activity.

RESULTS: Medication of IL-1 receptor antagonist leads to improved physical activity, a decrease in the concentration of lactat in the blood serum and a decrease in anxiety compared to untreated animals, which may indicate a milder course of chronic fatigue syndrome during the period of its maximum manifestations. Inhibition of peripheral cells of the immune system after administration of polyinosinic:polycytidylic acid and correction of this parameter with IL-1 receptor antagonist were shown. On the 10th day of the experiment, all parameters in the group of treated rats normalized and only TLR3 expression still remained elevated at the level of untreated rats which is regarded as activation of reparation processes.

CONCLUSIONS: The obtained data indicate that the use of the recombinant IL-1 receptor antagonist alleviates the manifestations of post-viral chronic fatigue syndrome in rats and completes the pathological process at an earlier date. With a recombinant IL-1 receptor antagonist is included in the treatment regimen for chronic fatigue syndrome in humans, positive results can also be expected.

Medical academic journal. 2024;24(4):97-108
pages 97-108 views

Nerve growth factor: impact on migration, clonogenicity, and bioenergetic metabolism of mitochondria of glioma U251 cells

Chernov A.N., Glushakov R.I., Landynya S.S., Sharapov Y.A., Galimova E.S., Shamova O.V.

Abstract

BACKGROUND: Glioblastoma is the most malignant tumor of the central nervous system. Temozolomide is the standard treatment for gliomas, and its use often leads to drug resistance and relapse of glioblastoma. Therefore, further research is needed to find other drugs that can improve the effectiveness of standard treatments.

AIM: The goal is to study the effects of nerve growth factor, temozolomide on clonogenicity, migration and energy metabolism of mitochondria of human U251 glioma cells.

MATERIALS AND METHODS: The study was conducted on human U251 glioma cells. A colony formation test was used to evaluate the ability of glioma cells to form colonies in vitro. Migration of U251 glioma cells was assessed by the Scratch Assay. To study mitochondrial metabolism in glioma cells, oxygen consumption rate and extracellular acidification rate were measured using the Seahorse XF CellMito and Seahorse XF Glycolysis Stress Test kits, respectively.

RESULTS: We found that nerve growth factor (7.55 × 10–3 µM) and temozolomide (155 µM) inhibited the clonogenicity of U251 glioma cells by 66.2% and 73.5–81.3% within 1–2 days, respectively. Exposure to nerve growth factor (7.55 × 10–3 µM) also suppresses U251 glioma cell migration on days 3 and 4. Temozolomide (155 µM) inhibits glioma cell migration on days 1–3. The anti-clonogenic and anti-migratory activities of nerve growth factor and temozolomide may be associated with their ability to reduce the basal rate of oxygen consumption, inhibit adenosine triphosphate synthetase and maximum mitochondrial respiration in human U251 glioma cells. Nerve growth factor and temozolomide did not affect glycolysis, glycolytic capacity, and glycolytic reserve in U251 glioma cells compared to controls.

CONCLUSIONS: Thus, nerve growth factor and temozolomide inhibit migration, clonogenicity, and bioenergetic metabolism of mitochondria in U251 glioma cells, exhibiting anti-mitogenic, anti-migration, and reducing energy metabolism effects.

Medical academic journal. 2024;24(4):109-123
pages 109-123 views

History of medicine

Dedicated to the memory of the staff of the Pavlov Biostation in Koltushi

Zakharova E.T., Kuznetsova T.G.

Abstract

The article presents the events associated with the opening of the Scientific and Experimental Biological Station in Koltushi. The events of one of Pavlov’s informal visits to the Biostation on September 26, 1929, to celebrate his 80th anniversary, are reconstructed from discovered archival photographs. The stories of Pavlov’s closest collaborators are told – a participant in the event described, physiologist Stanislav N. Vyrzhikovsky (1892–1937), the first head of the Pavlov Biostation and Pyotr M. Elagin (1879–1937), head of the dog kennel at the Biostation. After the murder of S.M. Kirov (December 1, 1934), the “Kirov Stream” descended on Leningrad in March 1935, sending out “superfluous people” called by the new government – church ministers, former tsarist officers, representatives of the nobility and merchant class. The former captain of the tsarist army, nobleman P.M. Elagin, was exiled from Leningrad with his family. Pavlov, who held Elagin in high esteem, achieved his return from exile. “As long as Pavlov is alive, they will not touch me,” the head of the Biological Station, former lieutenant of the tsarist army, nobleman S.N. Vyrzhikovsky, reassured his wife. On February 27, 1936, Ivan Petrovich died... In her memoirs, M.K. Petrova wrote, without naming names, about about two “suspicious employees” of the Biostation, expelled after Pavlov’s death. Today, few people know that these memoirs were about Elagin and Vyrzhikovsky, who died during the political repressions of 1937, whose names are good to remember in Pavlov’s anniversary year (1849–2024).

Medical academic journal. 2024;24(4):124-138
pages 124-138 views

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