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Vol 21, No 1 (2023)

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Reviews

Metabolic research from the standpoint of personalized medicine

Paltsev M.A., Zolnikova O.Y.

Abstract

One of the most important tasks of modern medicine is to recognize diseases at the preclinical stage, as well as to assess their development risks and their possible prevention. This dictates the need to use new, modern technologies aimed at the early detection of biomarkers and the identification of new therapeutic targets.

The purpose to summarize the available data on metabolomic studies used in medicine.

Material and methods. The analysis of the main foreign and domestic sources in the PubMed/Medline, RSCI/elibrary databases over the past 5 years was carried out.

Results. Metabolomics is a rapidly developing research method used in biomedicine to illustrate in detail the pathological mechanisms that occur and to develop new disease biomarkers. Analytical approaches used to study the metabolome are not inferior to genetic studies in their specificity and sensitivity. Along with this, the ability to simultaneously quantify several thousand metabolites in samples makes metabolomics a method oriented towards personalized medicine.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):3-7
pages 3-7 views

The use of mesenchymal stem cells in the treatment of osteoarthritis

Greben A.I., Shestakov D.Y., Eremin P.S., Kostromina E.Y., Markov P.A., Greben T.N., Gilmutdinova I.R.

Abstract

The purpose of the study was to analyze literature data on the use of mesenchymal stem cells as a conservative treatment of osteoarthritis.

Material and methods. Literature search was carried out using keywords: traumatology, orthopedics, mesenchymal stem cells, osteoarthritis, cell therapy. Out of 300 selected articles, 60 were used to write a review.

Results. Osteoarthritis treatment with mesenchymal stem cells has been shown to be effective and safe in cartilage repair in both animal and human studies. The review presents new literature data on therapeutic action mechanisms and elements of mesenchymal stem cells.

Conclusion. The analysis shows that a positive experience of using mesenchymal stem cells (MSCs’) for osteoarthritis treatment. However, before mesenchymal stem cells take their place in practical tools arsenal a lot of work must be done, specifically: phase III of clinical trials, clear criteria development defining cell culture as MSCs, development of production standards and further study of MSCs’ mechanism of action in osteoarthritis.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):8-15
pages 8-15 views

Modern method of SARS-CоV-2 combat

Bobkova N.V., Poltavtseva R.A., Chaplygina A.V., Sadykov V.F., Sukhikh G.T.

Abstract

Relevance: COVID-19 is the accepted name for an acute respiratory disease caused by the SARS-CoV-2 coronavirus. The suddenness, speed of spread, severity, and high lethality of COVID-19 have led many of the drugs used in the early stages of a pandemic to be based on emergency clinical observations rather than preclinical and clinical studies. Therefore, there is no doubt the relevance of systematizing effective therapeutic agents that prevent the severe course of a COVID-19 infection and reduce mortality, the creation of which is based on fundamental knowledge not only of the biology of the virus, but also of the patient’s response, which requires large-scale studies of pathogenesis and the study of predictors of a possible transition of the disease to severe and even the terminal phase.

Objective: A structured description of currently accepted medicines, vaccines, and approaches for the treatment of COVID-19.

Material and methods: a search was conducted in the PubMed database and the scientific electronic library eLIBRARY.RU. The selection of articles was carried out manually. This review includes 69 sources, including methodological recommendations of the Ministry of Health of the Russian Federation and data from ongoing clinical trials.

Results: medicines, vaccines and approaches to the treatment of COVID-19, currently adopted in different countries, are systematized, indicating the effectiveness and mechanisms of their action, as well as identified side effects that limit their use in certain groups of patients.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):16-29
pages 16-29 views

Premature aging (inflamaging) and diseases of the female reproductive system

Shteiman A.A., Krylova Y.S., Dokhov M.A., Zubareva T.S., Leontieva D.O., Botina A.V., Tikhomirova A.A.

Abstract

Relevance. The review is devoted to the issue of aging and the relationship of the molecular processes of aging with the pathology of the reproductive system

The aim of the study was to review the current understanding of aging, the mechanisms and role in the pathology of diseases such as endometriosis, premature ovarian failure and to find possible potential points of treatment.

Material and methods: the analysis and systematization of literature over the past 5 years in the PubMed, Scopus and Google Scholar databases was carried out.

Results. The review reflects the main mechanisms involved in the aging of the reproductive system, the impact on which is possible both by medication and by modifying lifestyle and nutrition. What can make it possible to reduce the number of side effects from the use of the main, hormonal, treatment

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):30-36
pages 30-36 views

Original research

Study of the relationship of iron concentration with the ferritin and transferrin in blood serum

Yurasov V.V., Sadykov A.R., Morozova G.D., Namiot E.D., Logvinenko A.A., Skalny A.V.

Abstract

Introduction. Iron is one of the main elements for the vital activity of the body. Iron deficiency leads to the development of iron deficiency anemia, one of the most common diseases in the Russian Federation; excess iron induces oxidative stress. In this way, the diagnostics of iron metabolism is an important applied problem.

The aim of the study. The aim of the study was to establish reference intervals for serum iron, measured not by the routine method, but by the ICP-MS method, on a large sample; study of gender and age fluctuations of the level of serum iron; study of the relationship between the concentration of iron and the levels of ferritin and transferrin in the blood serum.

Material and methods. The study was performed on the basis of a database of laboratory analyzes. The number of laboratory tests for ferritin, transferrin, iron in serum was 6786, 1809, 13161, respectively. When determining the reference intervals, the Hoffman method was used.

Results. It was found that the concentration of iron in the blood serum among women is lower than among men, and this tendency persists up to 45–50 years, there are no differences in the later age period. The concentration of serum iron positively and statistically significantly correlates with the level of ferritin in all age groups in the total sample and in the group of women; among men, statistically significant positive correlations were found only in the age groups of 18–25 years and older than 56 years. Correlations of iron concentration with the level of transferrin are less intense: statistically significant correlations were found in the total sample in the age groups of 26–35 years and 46–55 years.

Conclusion. When calculating the reference intervals of serum iron, it is necessary to consider the gender and age dynamics of deviations. Aging processes have a greater impact on iron metabolism for women than for men.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):37-42
pages 37-42 views

The effect of tuberculosis on the course of lung carcinoma in the experiment

Kudriashov G.G., Nefedov A.O., Tochilnikov G.V., Zmitrichenko Y.G., Krylova Y.S., Dogonadze M.Z., Zabolotnyh N.V., Gavrilov P.V., Azarov A.A., Davydenkova E.A., Vinogradova T.I., Yablonskiy P.K.

Abstract

Introduction. One of the problems of modern medicine is the low efficiency of treatment of patients with a coexistence of lung cancer and active tuberculosis. Optimal treatment regimens for coexistence pathology have not been developed at present. In recent years, fundamental research aimed to studying the unexplained mechanisms of the occurrence and course of coexistence pathology.

The aim of the study was to investigate the peculiarities of the effect of tuberculosis with different drug resistance on the course of lung carcinoma in an experiment.

Methods. The study was performed on 72 mice of the C57BL/6 line at the age of two months. To achieve the goal, three groups of laboratory animals were formed: Group 1 – mice infected with the reference strain Mycobacterium tuberculosis H37Rv, which underwent isolated transplantation of Lewis lung epidermoid carcinoma (n=24); Group 2 – mice infected with the clinical strain Mycobacterium tuberculosis 5582 with multidrug resistance, which underwent isolated transplantation of epidermoid lung carcinoma Lewis (n=24); Group 3 – uninfected mice that underwent isolated transplantation of Lewis lung epidermoid carcinoma (n=24). Clinical, radiological, morphological and bacteriological methods were used to compare the studied groups of animals. Statistical analysis was performed using the SPSS Statistica v23 software package.

Results. In group 3, there was significantly (p<0.01) more intensive weight gain by mice due to rapid tumor growth, in contrast to groups 1 and 2. Histological signs of pulmonary tuberculosis were detected in all infected mice (groups 1 and 2) in the form of productive pneumonia. The greatest increase in the lung mass coefficient was detected in group 2 compared to groups 1 and 3, which is explained by the subtotal spread of productive specific pneumonia when infected with a clinical drug-resistant strain of M. Tuberculosis. The lowest dynamics of lung mass coefficient was recorded in group 3. The worst survival was observed in group 2 (median was 22 days, 95% CI=21.4–22.6). Survival in groups 1 and 3 did not significantly differ and was 28 days in both groups (95% CI=25.3–30.7 in group 1, 95% CI=26.0–30.0 for group 3).

Conclusion. An experimental study showed that tumor progression slows down in M. tuberculosis infected animals compared to the control group. The coexistence of lung carcinoma and drug-sensitive tuberculosis is accompanied by the best prognosis. The coexistence of Lewis lung carcinoma and drug-resistant tuberculosis is accompanied by a large volume of lung tissue involvement and worse survival.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):43-49
pages 43-49 views

Features of experimental osteoarthrosis caused by dexamethasone and talc

Osmanova S.O., Osmanov O.O., Alimkhanova A.A.

Abstract

Introduction. An experimental study of the pathogenetic mechanisms of the development of inflammatory-destructive changes in the joints in animal models was carried out in order to develop new diagnostic strategies for further implementation of the results obtained in clinical practice, determination of morphometric and metabolic features of the skeletal connective tissue of the rat knee joints.

Material and methods. The authors studied histological preparations of knee joints stained with Mayer’s hematoxylin and eosin, alcian blue (pH 1.0 and 2.5) according to Van Gieson, Masson and Mallory. The metabolic properties of cartilage and bone tissue were studied by determining the concentration of hyaluronic acid, osteocalcin, and type I collagen in the blood serum of laboratory animals.

Results. In rats with osteoarthritis induced by the administration of dexamethasone and talc, a 50% decrease in the thickness of the articular cartilage in its loaded areas was noted. There was also a violation of the spatial distribution of chondrocytes, a decrease (p<0.01) in the nuclear-cytoplasmic ratio of chondrocytes to 0.3 and an increase in the serum concentration of hyaluronic acid (p<0.001) to 110.2 ng/ml, fragments of type I collagen (p<0.001) to 217.9 ng/ml and osteocalcin (p<0.001) to 231.1 ng/ml.

Conclusion. The main pathogenetic features of experimental osteoarthritis induced by dexamethasone and talc are a violation of the density of distribution, morphological features and functional activity of chondrocytes. All this leads to inhibition of the synthesis of the components of the extracellular matrix of the articular cartilage, and is also accompanied by the activation of the destruction of proteoglycans containing non-sulfated glycosaminoglycans.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):50-55
pages 50-55 views

The level of immune checkpoint co-inhibitors in tumor tissue in patients with colon tumor

Chetveryakov A.V., Tsepelev V.L.

Abstract

Introduction. A high level of checkpoint co-inhibitors in the tumor microenvironment plays an important role in inhibiting the local immune response, which contributes to the growth and progression of cancer.

The aim of the study. We aimed to determine immune checkpoint co-inhibitors level (CTLA-4, TIM-3, LAG-3, PD-1) and their ligands (B7-2, Galectin-9, PD-L1) in tumor tissue in patients with benign tumor of the colon and cancer.

Methods: the study enrolled 94 patients divided into 3 groups: 44 patients with colorectal cancer, 25 with a benign colon tumor, 25 – a control group (patients who underwent plastic surgery of a colostomy formed earlier due to a colon injury). The level of immune checkpoint co-inhibitors and their ligands was studied in tumor tissue by flow cytofluometry on a CytoFlex LX analyzer (Beckman Coulter, USA) using the LEGENDplex ™ HU multiplex analysis kit (Immune Checkpoint, USA)

Results: we found that in patients with colon cancer the level of immune checkpoint co-inhibitors (TIM-3, CTLA-4, LAG-3) in the homogenate supernatant of the tumor tissue was higher than in the control group. The level of TIM-3 protein increased by 43.6 times (p<0.001), CTLA-4 – by 2.3 times (p=0.007), LAG-3 – by 5.1 times (p<0.001). Patients with colorectal cancer also showed the elevation of the concentration of TIM-3 protein by 11.4 times (p<0.001), LAG-3 by 1.8 times (p=0.008), CTLA-4 protein by 1.5 times (p=0.02) compared to patients with benign colon tumor. In patients with colorectal cancer, the level of the TIM-3 ligand (Galectin-9) exceeded the indicator of the control group by 56.7 times (p<0.001), and the CTLA-4 ligand (B7-2) – by 1.7 times (p=0.004). In addition, the concentration of Galectin-9 in patients with CRC was 3.4 times higher (p<0.001), the B7-2 ligand was 1.5 times higher (p=0.04). compared to patients with benign colon tumor.

Conclusion: an increase in the level of CTLA-4, TIM-3, LAG-3 and their ligands – B7-2 and Galectin-9 in tumor tissue indicates the involvement of these molecules in the cancer genesis of colorectal cancer.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):56-60
pages 56-60 views

Combined effect of polypeptide complexes on the development of organotypic culture of rat tissues

Chalisova N.I., Ryzhak G.A., Egozova E.S.

Abstract

Introduction. The formation of effective bioregulators for the maintenance of the basic physiological functions, so as polypeptide complexes (PPCs), is one of the actual task of modern biology and medicine.

Purpose of study. Effect of combination of polypeptide complexes (PPCs) from thymus (Thymalin) with PPC from liver (Ventvil), PPC from kidney (Nephropept) and PPC from brain, (Сortexin) on the cellular proliferation of rat corresponding tissues.

Methods. Organotypic tissue culture of rat spleen, liver, kidney and brain cortex under different PPCs and their combinations effect.

Results. All PPCs increase statistically reliable the square index (SI) of rat corresponding tissues explants of young rats skin explants on 20–27%, as compared to the control. There was no potentiate effect and the stimulation of the cellular proliferation was at the account of this PPC, which stimulated the proliferation by its single effect.

Conclusion. The obtained data create a basis for using by the patient combined pathology of two different PPCs, each of them will have effect on the regeneration stimulation only of corresponding tissue.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(1):61-64
pages 61-64 views

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