Fedosov Alexey
@rudn.ru
FEDOSOV Aleksey
RESEARCH, TEACHING, or OTHER INTERESTS
Histology, Immunology
Scopus Publications
- EFFICACY OF USING MELATONIN PER RECTUM FOR EXPERIMENTAL ACUTE CEREBRAL ISCHEMIA
, MV Osikov, AV Shelomentsev, , , , MS Boyko, YuS Shishkova, AA Fedosov
Bulletin of Russian State Medical University, 2025
With limited efficacy and safety of the methods to treat ischemic stroke (IS), melatonin (МТ) can be considered a promising neuroprotective agent having a pleiotropic mechanism of action. The study aimed to assess the effect of MT contained in original rectal suppositories on the neurological status and microcirculation in the injury focus in experimental acute cerebral ischemia (EACI) in vivo. A total of 30 sexually mature rats were divided into three groups, 10 animals per group: shamoperated (SO) animals; animals with EACI; animals with EACI receiving original rectal suppositories weighing 100 mg with 2.5 mg of melatonin (МТ) throughout 7 days. On days 3 and 7, neurological status was assessed using the Garcia JH score, Placing test, Bederson test; microcirculation rate (MR) was assessed in the brain injury focus by laser flowmetry. A significant decrease in the Garcia JH scores by 58.3% (p = 0.001), Placing Test scores by 57.9% (p = 0.002), along with the significant increase in the Bederson Test scores in animals with EACI compared to SO animals was reported on day 3; the significant decrease in the Garcia JH scores by 75% (p < 0.001), Placing Test scores by 78.9% (p < 0.001) and the significant increase in the Bederson Test scores were reported on day 7. MR decreased by 30% on day 3 (p = 0.02), by 38% on day 7 (p = 0.005). The use of the MT-based rectal suppositories resulted in the neurological deficit restoration in the form of the significant increase in the Gаrcia JH scores by 53.3% (p = 0.008), Placing Test scores by 50% (p = 0.016) and the significant decrease in the Bederson Test scores by 50% (p = 0.029) on day 3; on day 7, the significant increase in the Garcia JH scores by 233% (p < 0.0001), Placing Test scores by 325% (p < 0.0001) and the significant decrease in the Bederson Test scores by 100% (p < 0.0001) were reported. MR increased by 12.5% on day 3 (p = 0.016), by 43.9% on day 7 (p = 0.005). The correlation analysis revealed the association between the neurological status and MR values: the neurological deficit improvement in animals with EACI in the context of receiving the MT-based rectal suppositories was associated with the MR increase in the ischemic focus in the brain. Thus, partial neurological status restoration in the context of using the MT-based rectal suppositories for EACI resulted from the MT vasoactive properties, which was reflected in the MR increase in the ischemic focus in the brain. - OXIDATIVE PROTEIN DESTRUCTION PRODUCTS AS MARKERS OF CHRONIC KIDNEY DISEASE PROGRESSION IN DIABETES MELLITUS
MV Osikov, LA Efros, LYu Zhuravleva, AA Fedosov
Bulletin of Russian State Medical University, 2025
Chronic kidney disease (CKD) represents one of the most common complications of type 1 diabetes mellitus (T1D). Oxidative stress (OS) can be considered as a key link of pathogenesis of CKD associated with T1D, therefore, identification of the redox status markers is important for prevention of the development and progression of this disorder. The study aimed to assess the substances generated during oxidative destruction of proteins and their correlation with glomerular filtration rate (GFR) in patients with T1D and stage 1–3 CKD. The study involved healthy individuals (n = 14), patients with T1D showing no signs of CKD (n = 30), as well as patients with T1D and stage 1 CKD (n = 60), stage 2 CKD (n = 38), and stage 3 CKD (n = 31). Healthy participants were matched to the index group by age and gender: 42.9% were males, 57.1% were females, the average age was 30.6 ± 4.2 years; body mass index, systolic and diastolic blood pressure, lipid profile were within normal. It has been found that patients with T1D and stage 1–3 CKD demonstrate plasma accumulation of early and delayed neutral and base products of oxidative protein modification (OPM): spontaneous 157% based on median, metal-induced 143% based on median relative to healthy individuals. We have revealed a decrease in overall antioxidant status (OAS) of plasma in 51% of patients with T1D and stage 3 CKD compared to patients with T1D without CKD. Estimated GFR, the integral indicator of renal function, decreases with increasing plasma levels of OPM products, decreasing OAS. The data obtained allow us to consider plasma levels of OPM products, OAS as affordable and informative methods to assess progression of early stage CKD in patients with T1D. - The Role of Changes in the Redox Status in the Pathogenesis of Chronic Lymphocytic Leukemia
M. V. Osikov, E. A. Korobkin, A. A. Fedosov, A.V. Sineglazova
Doklady Biochemistry and Biophysics, 2024
B lymphocytes with lymphocytosis, damage to the lymphatic organs, occurring in the older age group, the etiology and pathogenesis of which are not fully understood. Oxidative stress is an important factor in the regulation of stem cells and the activation of intracellular survival signaling pathways in chronic lymphocytic leukemia cells. The aim of the study was to analyze the current data on the role of redox status changes in the pathogenesis of chronic lymphocytic leukemia. A review of published relevant studies 2018-2023, scientific articles in scientific electronic bibliographic databases PubMed and Social Sciences Citation Index, devoted to the pathogenesis of chronic lymphocytic leukemia and the role of free-radical oxidation processes in it was carried out. In chronic lymphocytic leukemia, oxidative stress with a systemic excess of reactive oxygen species, an imbalance in the effectiveness of antioxidant defense is caused mainly by activation of oxidative phosphorylation in mitochondria, low levels of NADPH-oxidase type 2, increased expression of heme oxygenase-1, glutathione peroxidase and glutathione recycling enzymes, superoxide dismutase-2, thioredoxins and decreased expression of catalase. One of the mechanisms of resistance to drug therapy and oxidative stress of chronic lymphocytic leukemia cells is the intracellular signaling pathway dependent on erythroid nuclear factor-2, due to the activation of expression in cells of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, heme oxygenase-1, thioredoxin-1 and -2, reduced glutathione, natural killer cell activity, which is associated with lifespan, chemotaxis, proliferation, and survival. FOXO family proteins are believed to suppress carcinogenesis. FOXO3a increases the expression of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, and the activity of natural killer cells, which promotes the survival of tumor cells. The development of new targeted pharmacological agents that are capable of accumulating reactive oxygen species and reducing antioxidant protection due to the degradation of erythroid nuclear factor-2 and activation of NADPH-quinone oxidoreductase-1 is underway, which modernizes the therapy of chronic lymphocytic leukemia. - DYNAMIC CHANGES OF INFLAMMATORY MARKERS IN THE EARLY STAGES OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH TYPE 1 DIABETES MELLITUS
MV Osikov, LA Efros, LYu Zhuravleva, AA Fedosov
Bulletin of Russian State Medical University, 2024
Diabetes mellitus (DM) is one of the major factors contributing to the development and aggravation of chronic kidney disease (CKD). The accurate and convenient markers for early detection, estimation of progression, and adequate control of CKD therapy in individuals with DM are limited to glomerular filtration rate (GFR) and albuminuria. Given the role of chronic inflammation in the pathogenesis of DM and CKD, the study aimed to assess indicators of inflammation and the correlation of those with GFR in patients with type 1 DM (T1D) and early stage CKD. The study involved healthy individuals (n = 14), patients with T1D showing no signs of CKD (n = 30), as well as patients with T1D and stage 1 CKD (n = 60), stage 2 CKD (n = 38), and stage 3 CKD (n = 31). GFR was calculated using the formula СКD-ЕРI (eGFR); serum levels of IL1β and TNFα, C-reactive protein (CRP), and ceruloplasmin (CP) were determined by enzyme immunoassay; the neutrophil-to-lymphocyte index and the leukocyte intoxication index (LII) were calculated. It has been found that serum concentrations of IL1β, TNFα, CRP, and CP are elevated; LII and the neutrophil-to-lymphocyte index are increased. The inflammation and acute phase response severity progresses and reaches its maximum in stage 3b CKD, when the serum concentration of IL1β is increased 2.4-fold (р = 0.042), TNFα concentration by 34% (р = 0.005), CRP concentration 33-fold (р < 0.000), CP concentration by 73% (р = 0.008), LII 8.4-fold (р < 0.000), neutrophil-to-lymphocyte index 5-fold (р = 0.013). The integral kidney function indicator, eGFR, decreases with increasing serum levels of the above indicators. Thus, IL1β, TNFα, CRP, CP, LII, and the neutrophil-to-lymphocyte index can be considered as affordable and informative indicators for estimation of inflammation, the levels of which increase with progression of early stage CKD in patients with T1D. - RELATIONSHIP OF THE PHENOTYPE OF PERIPHERAL BLOOD LYMPHOCYTES AND SIGNS OF OSTEOPENIA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
M. V. Osikov, E. A. Korobkin, A. A. Fedosov, G. P. Dimov
Russian Journal of Immunology, 2024
Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries, characterized by the development of a number of complications, including osteoporosis, which is a prerequisite for studying its predictors. The purpose of the work is to investigate the relationship between immunophenotyping indicators of blood lymphocytes and osteodensitometry indicators in CLL. The study was conducted on 48 male patients with CLL aged 50-70 years with an average disease duration of 12 months and 14 apparently healthy men of the corresponding age (group 1). In the blood, CD5+, CD19+, CD20+, CD22+, CD23+, CD43+, and CD200+ lymphocytes were differentiated in the blood using flow cytometry. The international FRAX questionnaire was used to assess the probability of fracture. Osteodensitometry assessed bone mineral density (BMD), T-score (standard deviation, SD), Z-score (SD) in the lumbar spine (LS), proximal femoral neck (FNA), proximal femoral bone (PFB). Patients with CLL were included in group 2 (n = 34) with BMD within normal limits (T- and Z-score – 1.0 SD) or group 3 (n = 14) with signs of osteopenia (OP) (T- and Z-score from – 1.0 SD up to – 2.5 SD). In patients with CLL in group 3, compared with patients with CLL in group 2, there is a significant increase in the number of lymphocytes in the blood expressing markers CD5+, CD19+, CD20+, CD22+, CD23+, CD43+, and CD200+. In patients with CLL in group 3, signs of AP in the SPBC increase with the increase in lymphocytes with the CD5+, CD19+, CD20+, CD22+, CD23+, CD43+, CD200+ phenotype in the blood. Signs of AP in the PBC increase with the increase in lymphocytes with the CD5+, CD19+, CD20+, CD23+, CD43+ phenotype in the blood. The strongest connections were found between the number of lymphocytes in the blood with the markers CD5+, CD19+, CD23+, CD43+ and the T-score, Z-score, and BMD in the FNA. The data obtained are a prerequisite for further study of the interaction between the clone of tumor lymphocytes in CLL and cells involved in bone tissue remodeling to identify the mechanism of development of OP, osteoporosis and the risk of bone fractures, and changes in the quantitative composition of the lymphocyte phenotype in the blood can be considered as potential laboratory predictors of a decrease in BMD. - CURRENT IDEAS ON THE PATHOGENESIS OF OSTEOPOROSIS IN CHRONIC LYMPHATIC LEUKEMIA (LITERATURE REVIEW)
M. V. Osikov, E. A. Korobkin, A. A. Fedosov, A. V. Sineglazova
Acta Biomedica Scientifica, 2024
Background. Chronic lymphocytic leukemia (CLL) is the second most common hematological malignancy without a trend towards a decrease in its incidence. 66 % of patients with CLL experience bone fractures as a result of osteoporosis in all age groups, and the detection frequency is no more than 15 %. Insufficient understanding of the osteoporosis pathogenesis in CLL leads to problems in diagnosis, prevention and therapy.The aim of the study. To analyze modern data on the features of the osteoporosis pathogenesis in chronic lymphocytic leukemia.Results and discussion. Osteoporosis is formed when osteoresorption prevails over osteosynthesis due to intercellular interactions of bone tissue and the immune system, dysregulation of intracellular signaling pathways RANKL/RANK/OPG, Wnt, FoxO, RUNX2, initiated by cytokines, growth factors, prostaglandins, and hormones. The degree of osteoresorption in CLL is associated with the severity of the clinical course, chemotherapy and hormonal deprivation. The osteoporosis pathogenesis in CLL is considered as part of a complex set of events, including, firstly, the interaction between leukemic cells (overexpression of PTHrP, RANKL) and bone cells (synthesis of growth factors), which forms a vicious circle of osteoresorption and tumor growth. Secondly, pro-inflammatory markers in CLL (tumor necrosis factor α, interleukin (IL) 1β, IL-6, IL-8, IL-11, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, transforming growth factor β, prostaglandin E2) limit osteoblast-induced osteosynthesis and stimulate the expansion of osteoclasts from monocytic suppressor cells of myeloid origin with or without the participation of the RANKL/RANK system. Thirdly, oxidative stress in CLL and impaired efficiency of antioxidant protection with the participation of fibroblast growth factor 23, transcription factor Nrf-2 with activation of JNK, ERK1/2, NF-κB, and also an increase in the RANKL/OPG ratio lead to inhibition of osteoblastogenesis.Conclusion. Analyzing and systematizing data on the osteoporosis pathogenesis in CLL are instrumental for the development of diagnostic criteria for osteoporosis in chronic lymphocytic leukemia that are much-needed in clinical practice and for the improvement of therapeutic tactics. - CLINICAL AND IMMUNOLOGICAL ANALYSIS OF THE EFFECTIVENESS OF LOCAL APPLICATION OF VITAMIN D3 IN EXPERIMENTAL COLITIS
M. S. Boyko, M. V. Osikov, A. A. Fedosov, I. V. Grekova
Medical Immunology Russia, 2023
The pathogenesis of inflammatory bowel diseases has not been fully studied, and the therapies used have side effects that limit their use.The purpose of this study is to conduct a clinical and immunological analysis of the effectiveness of vitamin D3 in the original rectal suppositories in experimental colitis (EC).EC was modeled with oxazolone. Original suppositories with vitamin D3 in group 3 and 5-ASA in group 4 were used per rectum. The clinic was evaluated on the Disease activity index scale. The expression of MPO and TNFa, the content of neutrophils, lymphocytes, eosinophils, histiocytes, plasmocytes, fibroblasts, ulcerative defect, tissue damage index were determined in the focus of colon injury. The study was carried out on days 2, 4 and 6.With EC, DAI increases for the entire day, MPO and TNFa increase in the lesion, ulcerative defect isfixed, neutrophil-lymphocytic infiltration increases, and TDI increases. When comparing the morphometric parameters of the alteration zone in EC under the conditions of vitamin D3 use, in contrast to the use of 5-ASA, a decrease in the number of lymphocytes, an increase in fibroblasts was revealed on day 2, a decrease in the number of plasmocytes and an increase in fibroblasts on day 4, an increase in the number of histiocytes and fibroblasts on day 6. The diameter of the ulcerative defect and the TDI index have no significant differences between the compared groups. When comparing the effectiveness of vitamin D3, in contrast to the use of 5-ASA, the MPO content is higher on day 6; the TNFa content is higher on day 4.In EC, the effects of using rectal suppositories with vitamin D3 on clinical signs, the size of the ulcerative defect, the content of MPO and TNFa in the lesion are comparable to the effects of using rectal suppositories with 50 mg of 5-ASA; more pronounced with respect to the dynamics of the cellular composition of the lesion of the colon. - ROLE OF REDOX STATUS CHANGES IN THE PATHOGENESIS OF CHRONIC LYMPHOCYTIC LEUKEMIA
, MIKHAIL V. OSIKOV, EGOR A. KOROBKIN, , ALEKSEY A. FEDOSOV, , ALBINA V. SINEGLAZOVA, and
Vestnik Sovremennoi Klinicheskoi Mediciny, 2023
Introduction. Chronic lymphocytic leukemia is a hemoblastosis of CD5+ B lymphocytes characterized by lymphocytosis and damages to lymphatic organs and occurring in the older age group. Its etiology and pathogenesis have not been fully understood as of today. Oxidative stress is an important factor in the regulating the hemostasis of hemopoietic stem cells and in activating intracellular survival signaling pathways in chronic lymphocytic leukemia cells. Aim. This study is aimed at analyzing the current data on the role of redox status changes in the pathogenesis of chronic lymphocytic leukemia. Materials and Methods. We reviewed relevant studies published in 2018-2023 and research articles collected in scientific electronic bibliographic databases PubMed and Social Sciences Citation Index, dealing with the pathogenesis of chronic lymphocytic leukemia and the role of free-radical oxidation processes in it. Results and Discussion. In chronic lymphocytic leukemia, oxidative stress with a systemic excess of reactive oxygen species, an imbalance in the effectiveness of antioxidant defense is caused mainly by activation of oxidative phosphorylation in mitochondria, low levels of NADPH-oxidase type 2, increased expression of hemoxygenase-1, glutathione peroxidase and glutathione recycling enzymes, superoxide dismutase-2, thioredoxins, and decreased expression of catalase. Oxidative stress subsequences in the chronic lymphocytic leukemia cells include the activation of transcription factors related to erythroid nuclear factor, nuclear kappa B factor, and FOXO family transcription factors. One of the mechanisms of resistance to drug therapy and oxidative stress of chronic lymphocytic leukemia cells is the intracellular signaling pathway dependent on erythroid nuclear factor-2, due to the activation of expression in cells of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, heme oxygenase-1, thioredoxin-1 and -2, reduced glutathione, natural killer cell activity, which is associated with lifespan, chemotaxis, proliferation and survival. FOXO family proteins are believed to suppress carcinogenesis. FOXO3a increases the expression of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, and the activity of natural killer cells, which promotes the survival of tumor cells. Conclusion. The development of new targeted pharmacological agents that are capable of accumulating reactive oxygen species and reducing antioxidant protection due to the degradation of erythroid nuclear factor-2 and activation of NADPH-quinone oxidoreductase-1 is underway, which modernizes the therapy of chronic lymphocytic leukemia. - Influence of Rectal Ozone Application on the Intensity of Free Radical Destruction of Lipids and Intestinal Proteins in the Dynamics of Experimental Colitis
M. V. Osikov, E. V. Davydova, N. V. Kaigorodtseva, A. A. Fedosov, M. A. Il’inykh, K. S. Savchuk, L. V. Vorgova
Bulletin of Experimental Biology and Medicine, 2022 - Effectiveness of Experimental Colitis Therapy with Original Vitamin D3 Rectal Suppositories
M Osikov, M Boyko, A Fedosov, M Ilyinykh
International Journal of Biomedicine, 2022
Background: Pathogenesis of inflammatory bowel disease (IBD) is insufficiently explored, while most of the therapeutic agents used for IBD cases have undesirable side effects, which restrict their administration.The aim of this research was to study the influence of vitamin D3 formulated into original rectal suppositories on the parameters of clinical score, morphology, and oxidative lipid and protein destruction in the colonic lesion in the cases of experimental colitis (EC). Methods and Results: The experiment was performed on 98 Wistar male rats weighing 210-230 g. EC condition was induced by two-phase administration (dermal application and per rectum) of 3% alcohol solution of oxazolone. Originator polyethylene glycol-based suppositories, which contained 1500 МЕ of vitamin D3, were administered per rectum every 12 hours. Clinical score was defined according to the Disease Activity Index (DAI) scale. Morphometry was run using the software program “ImageScope M” (Russia). Damage of the colonic tissue was estimated on Tissue Damage Index (TDI). The following parameters were determined in the colonic lesion: neutrophil count (NC), lymphocyte count (LC), eosinophil count (EC), histiocyte count (HC), plasma cell count (PC), fibroblast count (FC), the diameter of the ulcerous defect, TDI, MPO expression, and TNF-α expression. The following parameters were determined in the damaged tissue homogenate: lipid peroxidation product count (LPP) and protein oxidative modification (POM) count. In cases of oxazolone-induced EC, on Days 2, 4, and 6, we registered clinical and laboratory signs, an ulcerous defect in the damaged area of the colon, all of which are typical for IBD conditions. There was an increase in DAI (peak on Day 6) and TDI (peak on Day 2). We also found an increase in NC (peak on Day 2), LC (peak on Day 6), EC (peak on Day 2), PC (peak on Day 2), HC (peak on Day 2), and FC (peak on Day 2). There was an increase in MPO expression (peak on Day 2) and TNF-α expression (peak on Days 2 and 4). We observed increases in the primary, secondary, and end LPP counts and the early-phase and late-phase POM counts in spontaneous and induced modes. An administration of 1500ME vitamin D3 rectal suppositories every 12 hours for 6 days decreased the severity of clinical manifestations and DAI. It reduced the area of the ulcerous defect and decreased the TDI on Days 4 and 6 of the experiment. On the background of using vitamin D3 rectal suppositories, we found a decrease in NC, EC, LC, and PC in the damaged area and an increase in HC and FC on Days 2, 4, and 6 from the start of the experiment. Administration of D3 rectal suppositories decreased МРО expression and TNF-α expression on Days 4 and 6 of EC. In the damaged area of the colon, we observed a decrease in the counts of the primary, secondary, and end LPP on Days 4 and 6 of the experiment. We also documented a decrease in the POM count in spontaneous mode on Day 2 and on Day 6 in induced mode. Conclusion: Vitamin D3 as a constituent of originator rectal suppositories in total dose 18,000 МЕ in the pre-clinical phase of EC decreases the intensity of EC clinical manifestations. It reduces the count of the cells that take part in tissue destruction in the colonic wall, of TNF-α and MPO expression levels, and LPP- and POM product count. It increases the count of the cells, which promotes tissue reparation. The obtained results are essential for carrying out further research aimed at elaboration of the mechanism of the D3 effect in cases of IBD and at its possible clinical use. - COMPARATIVE EFFECT OF OZONE EXPOSURE AND 5-AMINOSALICYLIC ACID IN OXAZOLON-INDUCED COLITIS UPON THE INDICES OF INNATE IMMUNITY
M. V. Osikov, N. V. Kaigorodtseva, M. S. Boyko, A. A. Fedosov
Russian Journal of Immunology, 2022 - The Effectiveness of Local Application of Melatonin in the Original Dermal Film in Experimental Thermal Trauma
M Osikov, A Ageeva, Yu Ageev, A Fedosov, K Nikushkina, Yu Loginova
International Journal of Biomedicine, 2021 - Role of mast cells in skin regeneration after thermal burn treated with melatonin-enriched dermal film
MV Osikov, AA Ageeva, AA Fedosov, VA Ushakova
Bulletin of Russian State Medical University, 2021 - Local antioxidant effect of original dermal film with melatonin in thermal injury
MV Osikov, EV Simonyan, AA Ageeva, YuI Ageev, AA Fedosov, AI Sinitsky
Bulletin of Russian State Medical University, 2020 - Aspects of free radical oxidation in the large bowel in ulcerative colitis and Crohn⇔s disease
MV Osikov, EV Davydova, MS Boyko, AE Bakeeva, NV Kaygorodtseva, IR Galeeva, AA Fedosov, MA Ilyinyh, LV Vorgova
Bulletin of Russian State Medical University, 2020 - The characteristic of proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of females with experimental chronic liver diseases of various aetiology
Morfologiia Saint Petersburg Russia, 2006
