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Vol 22, No 1 (2024)

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Reviews

Immune microenvironment in hepatocellular carcinoma: current concepts and the role of blockade of immune checkpoints

Bueverova E.L., Zolnikova O.Y., Paltsev M.A.

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. The specificity of the immune microenvironment of an organ limits the possibilities of traditional therapeutic and surgical approaches to treatment, therefore one of the most important tasks of modern medicine is the search for new therapeutic targets targeting the tumor microenvironment. The introduction of checkpoint inhibitors into clinical practice expands immunotherapeutic options in the fight against liver cancer.

The purpose of our review is to summarize the available data on the liver immune microenvironment in hepatocellular carcinoma and to present advances in cancer immunotherapy using immune checkpoint blockade.

Material and methods. An analysis of the main foreign and domestic sources was carried out using the PubMed/Medline, ClinicalTrials.gov databases over the past 5 years.

Results. In terms of morbidity and mortality, hepatocellular carcinoma is included in the list of the most common malignant neoplasms in the world and the forecasts for the coming decades are disappointing. Modern approaches to immunotherapy, taking into account the tumor microenvironment, are associated with better survival rates and safety profiles than standard therapy.

Conclusion. The effectiveness of checkpoint inhibitors as monotherapy and combination strategies offers hope for improving the prognosis and quality of life of patients with unresectable HCC.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):3-12
pages 3-12 views

Interleukin-11 and cardiovascular pathology

Alieva A.M., Nikitin I.G., Valiev R.K., Baykova I.E., Kotikova I.A.

Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. An important task in cardiology is the search and study of new biomarkers. Scientific interest is actively focused on the study of interleukin-11 (IL-11).

The purpose of the literature review was to analyze experimental and clinical studies devoted to the study of IL-11 as a diagnostic and prognostic marker in CVD.

Material and methods. The article provides an overview of current publications. An analysis of literature sources was carried out, including all relevant publications in the databases PubMed, RSCI, MedLine, Google Scholar, Science Direct.

Results. In endothelial cells, IL-11 primarily promotes angiogenesis, thereby exerting a beneficial effect on coronary heart disease. IL-11 also promotes vascular remodeling by inducing smooth muscle cell transformation and fibroblast activation. IL-11 may be involved in the onset and progression of pulmonary hypertension through the JAK/STAT3 pathway and aortic dissection processes through the non-classical ERK pathway.

Conclusion. The presented literature review indicates the potentially important diagnostic and prognostic value of IL-11 assessment. Regulating the concentration and expression of IL-11 may be a promising strategy for the treatment of CVD.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):13-20
pages 13-20 views

Biomarkers of endothelial damage and their role in predicting the development of sepsis and septic shock

Khomyakova T.I., Babaev M.A., Ponomarenko E.A., Khomyakov Y.N.

Abstract

Introduction. Sepsis is multiple organ dysfunction in response to the generalization of an infectious process. The likelihood of developing sepsis correlates with the value of biochemical parameters, which can serve as prognostic markers. The endothelium, as the structural basis of the circulatory system, is primarily exposed to pathogenetic factors, performing a protective function.

The purpose of this review was to summarize the results of assessing the diagnostic and prognostic effectiveness of molecular markers of endothelial damage in the development of inflammation, sepsis and septic shock.

Material and methods. The literature search was conducted using the databases PubMed/Medline, Elsevier.com., ResearchGate, RSCI/elibrary, over the past ten years.

Results. Using keywords, 215 articles were found and analyzed, from which 70 of the most significant and reliable sources were selected. It was concluded that it is necessary to develop a panel of markers of endothelial damage, which together will provide high reliability and specificity for assessing the risk of developing sepsis and septic shock.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):21-28
pages 21-28 views

Original research

Trace elements and the inflammatory process development: predictive possibilities

Morozova G.D., Logvinenko A.A., Grabeklis A.R., Nikolaev S.E., Sadykov A.R., Yurasov V.V., Skalny A.V.

Abstract

Introduction. Late diagnosis of inflammatory pathologies leads to increased risks of chronicization of the process, generalization, development of complications, and reduced effectiveness of therapy. Routine methods of clinical laboratory diagnostics often have diagnostic value at the stage of already developed disease with pronounced clinical manifestations. Determination of blood serum trace elements may have prognostic value in the diagnosis of inflammatory diseases. The trace elements most extensively studied in the context of inflammation and immune defense are copper and zinc.

The aim of the study. The aim of the study was to investigate the prognostic significance of determining copper and zinc concentrations in serum in the diagnosis of inflammation.

Material and methods. Concentrations of CRP, ferritin, ceruloplasmin, leukocytes, neutrophils, fibrinogen, copper, and zinc were determined in 1153 examined people aged 18 to 86 years. Serum trace elements were determined by ICP-MS method, the rest of the parameters were measured by standard methods. ROC analysis was used to evaluate the prognostic significance of serum copper and zinc measurements. Positive predictive value and negative predictive value were also calculated for the laboratory tests.

Results. It was shown that serum copper concentration in both men and women can be used as a predictor of abnormalities of CRP, ceruloplasmin, and fibrinogen. By abnormalities in serum copper concentration, it is possible to predict increased leukocytes in men and women; decreased leukocytes in men; and increased neutrophil levels in men and women. The prognostic significance of the laboratory test for serum zinc was found in relation to the detection of ferritin deficiency in women and ceruloplasmin deficiency in men and women.

Conclusion. The results obtained in the study suggest the possible use of serum copper and zinc laboratory tests for prognostic purposes.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):29-34
pages 29-34 views

Effectiveness and safety of carboplatin-containing antitumor therapy regimens in a model of coexistance of lung carcinoma and tuberculosis

Kudriashov G.G., Zmitrichenko Y.G., Vinogradova T.I., Dogonadze M.Z., Zabolotnyh N.V., Dyakova M.E., Esmedlyaeva D.S., Tochilnikov G.V., Nefedov A.O., Krylova Y.S., Yablonskii P.K.

Abstract

Introduction. Treatment of the coexistent pathology of lung cancer and tuberculosis remains the prerogative of experimental research, since the optimal treatment strategy for the coexistence of these two diseases has not yet been developed. The purpose was to study the effectiveness and safety of carboplatin-containing antitumor therapy regimens in combination with anti-tuberculosis chemotherapy.

Material and methods. The study was conducted on 64 C57BL/6 mice aged two months with a previously modeled coexistant pathology of lung carcinoma and tuberculosis. Depending on the therapy, 4 groups were formed: 1 – control without treatment (n=16), 2 – antitumor (carboplatin + paclitaxel) + antituberculosis therapy (n=16), 3 – antitumor (carboplatin + pemetrexed) + antituberculosis therapy (n=16), 4 – antitumor (carboplatin + gemcitabine) + anti-tuberculosis therapy (n=16). The anti-tuberculosis therapy regimen included the administration of isoniazid, rifampicin, pyrazinamide and ethambutol. The antitumor effect (tumor growth index, tumor growth inhibition), antituberculosis effect (CFU per lung weight), toxicity (clinical blood test parameters, biometric indicators of internal organs), and survival were assessed. Statistical processing was carried out using non-parmetric statistics methods.

Results. The lowest average body weight was recorded in group 4 from 7 to 21 days. The greatest differences between groups in the volume of the tumor node were observed from 12 to 16 days of the experiment under the influence of antitumor drugs. At the same time, the greatest inhibition of tumor growth was observed in group 4. On day 9 in group 2 there were signs of the myelo-immunosuppressive effect of antitumor therapy in the form of a decrease in the concentration of leukocytes, lymphocytes and monocytes. In the study groups, there were no statistically significant differences in the survival rate of the experimental and control groups. In all experimental groups, significantly lower spleen MC values were recorded, and in group 4, significantly lower liver MC values were also recorded. The highest level of mycobacterial load was recorded in the control group. The lowest CFU per lung weight was found in the carboplatin and gemcitabine treatment group.

Conclusion. Carboplatin-containing chemotherapy regimens for lung carcinoma in tuberculosis-infected mice have both antitumor and antituberculosis effects. The most pronounced antimycobacterial activity was recorded when using a combination of antituberculosis therapy with carboplatin and gemcitabine.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):35-42
pages 35-42 views

Mitochondrial proteins as biomarkers of occupational disease risk of pilots and astronauts

Leontyeva D.O., Zubareva A.S., Korovin A.E., Grishin A.P., Tovpeko D.V., Fedotkina T.V., Churilov L.P.

Abstract

Introduction. Mitochondrial dysfunction is an important pathogenic mechanism of neurodegeneration, characterized by a progressive structural and functional loss of neurons, leading to heterogeneous clinical and pathological manifestations with subsequent impairment of the functional anatomy of the brain.

Aim of research. To study the influence of occupational hazards and stress experienced by civil aviation pilots and cosmonauts on the expression of mitochondrial biomarkers in buccal epithelial cells to assess the risk of developing neurodegenerative processes.

Material and methods. The study involved 23 male participants in two age groups. 4 groups of investgation were formed, according to the occupation, comparable in age. The expression of mitochondrial proteins prohibitin and parkin in the buccal epithelium of the study participants was assessed by immunohistochemical methods.

Results. A decrease in the expression level of the prohibitin protein was found in the group of civil aviation pilots compared to the control group of the corresponding age. There was also a tendency to a decrease in the level of expression of the studied proteins prohibitin and parkin in the group of cosmonauts compared with the control group of the corresponding age.

Conclusion. The results obtained indicate a mitochondrial dysfunction, which may increase the risk of developing neurodegenerative changes.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):43-51
pages 43-51 views

Biomechanical properties of nasal tissues

Gvetadze R.S., Yarygin N.V., Muslov S.A., Ovchinnikov A.Y., Arutyunov S.D., Sukhochev P.Y.

Abstract

Introduction. Plastic rhinosurgery and augmentation rhinoplasty are very relevant today. Especially in relation to patients with congenital saddle deformity of the nasal dorsum, as well as patients with iatrogenic disorders of the nose shape, which dramatically reduce the quality of human life. There are violations of the function of the nose. The purpose of the work.

Purpose. Within the framework of the necessity of performing silicone implantation rhinoplasty, the strength, elastic and hyperelastic properties of the soft tissues of the nasal fascia and periosteum were studied, the dynamic viscosity of the tissues of the nasal fascia and periosteum was evaluated, determining their relaxation properties using elastic, hyperelastic and rheological models.

Methods. Linear, bilinear (with two Young modules), exponential, hyperelastic (neohookean, Mooney-Rivlin, Ogden, Yeoh, polynomial and Veronda-Westmann) and elastic-viscous (Maxwell) models of biological tissues were used. We used the Mathcad 15.0 computer algebra system and the universal package of interdisciplinary programs ANSYS Multiphysics Software (version 2022 R2). The accuracy of replacing the properties of real tissues with the results of calculations was calculated on the basis of indicators of descriptive statistics (standard deviation, maximum absolute error, maximum relative error and correlation coefficient).

Results. It is proved that the bilinear model for the exact reproduction of the stress-strain curve assumes at the molecular level of tissues an initial linear reaction of elastin fibers, passing at ε=εcr into the final linear reaction of the collagen matrix. It was found that the properties of the periosteum (correlation coefficient R=0.9999) and nasal fascia (correlation coefficient R=0.9999) are described most adequately by the 5-parametric polynomial model of the 2nd order and the Yeoh model of the 3rd order (R=0.999 and R=1, respectively), the least accurately by the simple 1-parameter neohookean model (R=0.898 for the periosteum and R=0.905 for the fascia). Among elastic models, the exponential dependence characterizes the behavior of nasal materials quite well.

Conclusion. Biomechanically verified that the periosteum is thicker, stronger and more rigid than the fascia. The established very high viscosity values indicate the slowness of relaxation processes in tissues. The periosteum relaxes tension more slowly, which improves the result of implant fixation. On the contrary, the relaxation time of the periosteum is higher than that of the fascia, from which it is concluded that it is preferable not to cut the periosteum during subcostal implantation.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):52-59
pages 52-59 views

Evaluation of the effect of neuropeptides of the melanocortin family on stress-associated changes in the level of corticotropin-releasing hormone and corticosterone

Yasenyavskaya A.L.

Abstract

Introduction. To date, the problem of studying the neuropeptide system of regulation of adaptive processes is relevant, since the stress reaction is a trigger for the occurrence of various diseases, in particular depression. Corticoliberin is considered as the main regulator of the hypothalamic-pituitary-adrenal axis, released in response to stress from the paraventricular nucleus of the hypothalamus, modulating the synthesis of adrenal hormones and further the processes of integration of neuroendocrine, autonomic and behavioral responses to stress.

The aim of the study was to evaluate the effect of neuropeptides on stress–induced changes in corticotropin-releasing hormone and corticosterone.

Material and methods. The experiment was carried out on male rats in the amount of 70 individuals, which were divided into several groups: a group of intact animals receiving an equiobject of water solution for intraperitoneally injection for 20 days (10 individuals), a group of animals receiving an equiobject of water solution for intraperitoneally injection in an experimentally created model of a depressive-like state for 20 days (20 individuals); experimental groups of animals who received intraperitoneally studied neuropeptide compounds Met-Glu-His-Phe-Pro-Gly-Pro and His-Phe-Arg-Trp-Pro-Gly-Pro at a dose of 100 mcg/kg/day for 20 days from day 1 of an experimentally created model of a depressive-like state. A depressive-like state was modeled by daily intermale confrontations for 20 days, as a result of which submissive and aggressive types of behavior were formed in rats. Neuroendocrine status was assessed by determining the level of key hormones of the hypothalamic-pituitary-adrenal axis (corticotropin-releasing hormone (corticoliberin) and corticosterone) in blood serum using enzyme immunoassay (ELISA).

Results. In conditions of stress-induced depression, a statistically significant increase in corticoliberin and corticosteroid in the blood of rats of both types of behavior was found, the difference in comparative aspect with the indicators of the control group, while exposure to neuropeptides against the background of stressful exposure contributed to a decrease in corticosterone levels by an average of 30% (p<0.05).

Conclusion. Thus, it was found that stress-induced depression is accompanied by hyperactivation of the hypothalamic-pituitary-adrenal axis, presumably due to a violation of the reverse inhibitory effects of endogenous glucocorticoids due to dysfunction of glucocorticoid receptors, which contributes to the development of a complex of manifestations of the main reactions, in particular, a decrease in the level of neurotrophic factors and the development of neurogenic inflammation. Neuropeptides of the glyproline series, in turn, showed the ability to reduce the activity of the hypothalamic-pituitary-adrenal axis by inhibiting the level of corticoliberin and corticosterone in conditions of stress-induced depression.

Molekulyarnaya Meditsina (Molecular medicine). 2024;22(1):60-64
pages 60-64 views

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