Molekulyarnaya Meditsina (Molecular medicine)

The study of immune checkpoint expression by tumor microenvironment T-lymphocytes is necessary for understanding the pathophysiological mechanisms of tumor immunosuppression, as well as for the development of new methods of targeted therapy for colorectal cancer (CRC).

Objective. To study the expression of immune checkpoints by T-lymphocytes in the tumor microenvironment of patients with colon cancer.

Material and methods. The level of expression of immune checkpoints (CTLA-4, PD-1, TIM-3) by tumor microenvironment T-lymphocytes in 105 patients with stage III colorectal cancer was studied using flow cytometry. The control group consisted of 75 patients with non-neoplastic diseases of the colon.

Results. In patients with CRC, the expression of the co-inhibitory protein CTLA-4 on T-helpers increases by 5.5 times and on cytotoxic T-lymphocytes of the tumor microenvironment by 1.9 times. The level of PD-1 expression by CD4-positive T-lymphocytes in the group of patients with CRC exceeds the similar indicator in the control group by 1.8 times. In CRC, the relative content of CD8⁺TIM-3⁺ lymphocytes in the tumor microenvironment is 2.5 times higher than the similar indicator in the control group. A statistically significant threshold for exceeding the level of CTLA-4, PD-1 and TIM-3 protein expression on the surface of T-lymphocytes of the tumor microenvironment in colorectal cancer relative to the control group was established. For the CTLA-4 protein, this indicator was 14.7% or more on T-helpers, for the PD-1 molecule – more than 41.9% on CD4-positive lymphocytes and TIM-3⁺ – more than 6.1% on cytotoxic T-lymphocytes.

Conclusion. In patients with colon cancer, the expression of the co-inhibitory protein CTLA-4 on the surface of both T-helpers and cytotoxic T-lymphocytes, the PD-1 molecule on CD4-positive cells and TIM-3 on CD8⁺ lymphocyte increases in the primary tumor site.

Introduction. Bacterial lipopolysaccharide (LPS) affects the structure and function of nervous tissue cells.

The aim of the study: to explore the impact of intraperitoneal LPS given to mice on levels of such markers as glial fibrillar acidic protein (GFAP), adapter protein binding ionized calcium (Iba1), tumor necrosis factor alpha (TNF-α), and caspase-3 in the cingulate cerebral cortex.

Material and methods. C57Bl/6 mice aged 3 months were injected with saline solution (control group) or escherichial LPS at a dose of 1 mg/kg of body mass (comparison group) once a day for 4 consecutive days. On Day 5, the animals were sacrificed with further coronal sections of the brain of 5 µm done and staining provided with immunofluorescent antibodies to GFAP, Iba1, TNF-α, and caspase-3.

Results. Animals of the comparison group had the number of GFAP- and Iba1-positive cells in the cingulate cortex that was significantly larger than in animals of the control group. The area of the ground substance with a positive antibody reaction to TNF-α in the mice of the comparison group stayed increased, and the area of the cytoplasm with a positive antibody reaction to caspase-3 did not differ between the groups.

Conclusion. The revealed levels for GFAP and IBA1 markers with the increased content of TNF-α in the ground substance of the nervous tissue without changes in the levels of caspase-3 in the cytoplasm of cells suggest a significant role of TNF-α release in the reaction of neuroglia to LPS. It is necessary to further study the morphological changes in the nervous tissue in the applied mode of administration of LPS.

Aim. To substantiate the pathogenetic rationale for including aqueous solution of dihydroquercetin (taxifolin) in the comprehensive treatment of diabetic foot and to present the results of a case series on the application of this form in patients with trophic ulcers receiving standard treatment, as well as to compare the obtained results with current data on the molecular mechanisms of taxifolin action.

Methods. A prospective observational study (case series, n = 15) in patients with severe diabetic foot receiving standard therapy supplemented with aqueous dihydroquercetin per os and topically as a gel. The dynamics of ulcer healing (area, depth, granulation), laboratory markers of inflammation and oxidative stress (including malondialdehyde levels), and quality of life according to the SF-36 questionnaire were evaluated. Additionally, to compare the clinical results obtained with global practice, a targeted analysis of publications in PubMed, Scopus, and eLIBRARY databases for 2019–2024 was conducted on the pathogenesis of diabetic foot and the use of taxifolin/dihydroquercetin.

Results. Complete ulcer healing within 6–10 weeks was achieved in 13 out of 15 patients (86.7%), while 2 patients (13.3%) showed a significant reduction in ulcer area (~75%) without complete closure by the end of the observation period. The mean reduction in ulcer area was 68  ±  18%, accompanied by decreased levels of C-reactive protein, malondialdehyde, leptin, and insulin, as well as improved quality of life scores on the SF-36 questionnaire. No adverse events related to the intake of aqueous solution of dihydroquercetin (taxifolin) and topical application of gel formulations based on it were registered. The obtained data are consistent with the concept of the key role of oxidative stress and microangiopathy in the pathogenesis of diabetic foot and indicate the potential of dihydroquercetin as an adjuvant component of comprehensive therapy in comorbid patients.

Conclusion. Based on the presented case series, the integration of aqueous solution of dihydroquercetin (taxifolin) into personalized comprehensive therapy for diabetic foot in comorbid patients appears promising, accelerating ulcer healing with satisfactory tolerability according to observational data; the obtained results are consistent with available experimental and clinical data from global literature, but require confirmation in randomized controlled trials.

Relevance. Primary malignant neoplasms of bones and articular cartilage account for about 0.2% of all cancer cases and are characterized by an aggressive course, high tendency to metastasize, and resistance to therapy, which leads to unsatisfactory survival rates, especially at late stages. Existing diagnostic methods (visualization, biopsy) are associated with risks and have limitations, including the lack of specific immunohistochemical markers and insufficient sensitivity for early detection of these diseases.

Objective. A review of the literature to assess the use of “liquid biopsy” based on blood exosomes for the diagnosis and monitoring of malignant neoplasms of bones and articular cartilage.

Material and methods. The work used data from 46 articles devoted to the study of the composition and functions of exosomes, their role in the oncogenesis of malignant neoplasms of bones and articular cartilage, as well as the results of studies on the use of the molecular cargo of exosomes as a source of potential biomarkers.

Results. It has been established that miR-25-3p has a high diagnostic potential for diagnosing osteosarcoma, miR-525 for chondrosarcoma, and miR-152 and miR-34a for Ewing’s sarcoma, which are involved in regulating the proliferative activity of tumor cells. Thus, analysis of exosome contents allows us to determine the tumor type, predict the response to therapy and the risk of metastasis, overcoming the limitations of traditional biopsy.

This review was conducted to systematize data on the association of matrix proteinase gene polymorphisms (MMP, ADAMTS, ADAM) with the risk of developing osteoarthritis.

Material and methods. A systematic literature search of PubMed and Web of Science databases for the period 2003–2024.

Results. Significant ethnic and population heterogeneity in the distribution of genetic associations was revealed. The most compelling data were obtained for ADAMTS-5 (rs2830585, rs2249350) and ADAMTS-14 (rs4747096) gene polymorphisms, demonstrating reproducible associations across various populations. However, for many other candidate genes (ADAMTS-7, -12, MMP-1, -3, -13), conflicting results are observed, due to both methodological limitations of the studies and true population differences.

Conclusion. The obtained data highlight the complex polygenic nature of hereditary predisposition to osteoarthritis and the need to integrate genetic data with functional studies to establish causal relationships.

Introduction. Ascorbic acid (vitamin C) is an essential cofactor of numerous enzymatic reactions and possesses pronounced antioxidant properties. Recent years have seen accumulating evidence of its immunomodulatory effects, particularly the ability to potentiate antiviral response. RNA interferon inducers represent a class of immunomodulators that activate innate immunity through pattern recognition receptors. The combination of ascorbic acid with RNA inducers may provide a synergistic effect in activating antiviral defense.

Objective: to systematize current data on molecular mechanisms of immunomodulatory action of ascorbic acid, analyze possible pathways of synergistic interaction between vitamin C and RNA interferon inducers, and evaluate therapeutic potential of combined preparations.

Material and methods. A systematic analysis of scientific literature in PubMed, Scopus, Web of Science, eLibrary databases for 2000–2025 was conducted using key terms: ascorbic acid, vitamin C, interferon inducers, RNA PAMP, innate immunity.

Results. Ascorbic acid is involved in the regulation of innate and adaptive immunity through multiple mechanisms: it serves as a cofactor for the TET and JmjC family of dioxygenases, which regulate epigenetic modifications in immune cells; modulates the activity of the NF-κB and HIF-1α transcription factors; enhances neutrophil phagocytosis and chemotaxis; and supports the function of NK cells and T lymphocytes. Interferon RNA inducers activate TLR3, TLR7/8, RIG-I, and MDA5 receptors, triggering the IRF3/7 and NF-κB cascades with subsequent production of type I interferons. Synergism can be realized through: increased expression of pattern recognition receptors under the influence of ascorbate; potentiation of IRF and NF-κB signaling pathways; protection against oxidative stress induced by activation of innate immunity; optimization of the energy metabolism of immune cells. Combination drugs containing ascorbic acid and RNA components demonstrate more pronounced antiviral activity compared to monocomponents.

Conclusion. The combination of ascorbic acid with RNA interferon inducers represents a rational strategy for enhancing antiviral immunity. Development of combined preparations based on this principle opens prospects for creating effective and safe means of prevention and therapy of viral infections.

The aim of this review is to systematize current knowledge on the role of selenium in biochemical processes and in the development of diseases associated with its deficiency or excess.

Material and methods. A comprehensive search and analysis of publications from 2005 to 2025 were conducted in the PubMed, Scopus, and Elsevier databases. Selenium (Se) is an essential trace element important for human health due to its involvement in the formation of selenoproteins, which perform antioxidant, anti-inflammatory, and regulatory functions. Many selenoproteins play a key antioxidant role, protecting cells from reactive oxygen species and maintaining redox homeostasis. This is essential for a number of biological processes, including intracellular signal transduction and modulation, cell proliferation, immune system function, cellular aging, ferroptosis, reduction of DNA damage and preservation of telomere length and others. An important function of certain selenoproteins is their indirect participation in the synthesis of thyroid hormones and the regulation of their activity in tissues. Thyroid hormones, in turn, control metabolic processes in virtually all tissues of the body.

Results. This review summarizes contemporary insights into the biochemical functions of selenium, its importance for the immune, endocrine, reproductive, cardiovascular, and nervous systems, as well as the consequences of its deficiency or excess in the body. Systematic analysis of the literature confirms that selenium deficiency is associated with increased susceptibility to viral infections (including COVID-19), thyroid dysfunction, an elevated risk of developing cardiometabolic, neurodegenerative, and oncological diseases, male infertility, adverse pregnancy outcomes, a higher risk of congenital hypothyroidism, and impaired growth and development in children. An additional important aspect is the potential role of selenium in the detoxification of heavy metals, endotoxins, and mycotoxins, and increasing the effectiveness of certain antitumor drugs. However, excessive intake of selenium increases the risk of its toxic effects.

Conclusion: The collected and analyzed data emphasize that selenium is an essential trace element for maintaining “metabolic health” and preventing various diseases. Both selenium deficiency and excess can have detrimental effects on human health, highlighting the need for more thorough investigation of this issue. Future studies evaluating selenium concentrations and the levels of its specific transporters in blood may facilitate the development of personalized approaches to the prediction, diagnosis, and treatment of diseases associated with selenium imbalance.