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Vol 19, No 2 (2021)

Articles

Protocol to evaluate clinical tumor tissue sample for genetic studies

Borbat A.M., Yatsenko I.V.

Abstract

The article represents a literature review on the molecular genetic methods with routine histological material for clinical purposes within oncology service. The protocol to evaluate the quality of tumor tissue samples for molecular genetic studies is proposed. The protocol includes a sample identification section, a descriptive section containing tumor tissue evaluation, necrosis within a sample, background tissue and tissue artifacts, summary, and graphical schema of the slide to measure tissue area. The protocol is accessible for download as a pdf file. The protocol should improve the standardization of the procedure and communication between laboratory departments and increase the quality of medical service.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):3-7
pages 3-7 views

On the role of PCSK9 in the development of atherosclerosis: molecular aspects

Chaulin A.M., Duplyakov D.V.

Abstract

Due to the discovery of the proprotein convertase subtilisin/kexin type 9 (PCSK9) and the establishment of its role in lipoprotein metabolism, it became possible to deliver new groups of effective drugs for the treatment of dyslipidemia. The main function of PCSK9 is to eliminate low-density lipoprotein receptors leading to the development of hypercholesterolemia - one of the key risk factors for atherosclerosis and cardiovascular diseases. Therefore, inhibition of PCSK9 has become a new strategy for hypolipidemic measures. Monoclonal antibodies (class G immunoglobulins) against PCSK9 - alirocumab and evolocumab are currently approved for the use in clinical practice. At the stage of development and clinical trials, there are many additional groups of drugs acting as inhibition of PCSK9 gene expression, PCSK9 matrix RNA translation, and inhibition of the function of the PCSK9 enzyme. This review examines the role of PCSK9 in the regulation of lipoprotein metabolism and describes in detail the molecular mechanisms for regulating the expression of the gene encoding PCSK9. The main groups of new hypolipidemic anti-PCSK9 drugs are also discussed: monoclonal antibodies against PCSK9, small interfering RNAs, antisense nucleotides, small molecules, and the anti-PCSK9 vaccine.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):8-15
pages 8-15 views

Hormone adropine: its effect on age-associated diseases

Kuznik B.I., Chalisova N.I.

Abstract

The purpose of the review was the search and analysis of the data about hormone adropin, similar to the known hormone irisin, and its effect on the pathology, associated with aging. Adropin is expressed in many following organs as referred to CNS, in liver, kidney, heart, pancreas, jejunum, in endothelial cells, milk, foremilk. The effect of adropin is related to the regulation of energetic balance, glucose, and fatty acid metabolism. The adropin concentration is decreased with the age but is increased by the physical loading. Adropin plays a great role in CNS function and its concentration is decreased in blood and brain by the neurodegenerative diseases. Experiments in animals demonstrated, that adropin can decrease the degenerative symptoms in CNS. The adropin concentration in blood is decreased by the pathology of the cardiovascular system, by diabetes melitus, metabolic syndrome, cancer of mammary gland, and endometrium. A negative correlation is detected between the adropin concentration and arterial pressure, endothelin concentration and insulin resistance, and positive correlation between cardial troponin and natrium-uretic peptide. Adropin is beleived to play a great role in the development of pathology, associated with aging.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):16-25
pages 16-25 views

Features of expression of ß-amyloid in cerebral endothelial cells in experimental Alzheimer’s disease

Gorina Y.V., Osipova E.D., Morgun A.V., Lopatina O.L., Kharitonova E.V., Salmina A.B.

Abstract

Introduction. The formation of neurofibrillary plexuses and the accumulation of senile plaques in the parenchyma and cerebral vessels are the key pathological signs of Alzheimer’s disease presenting a neurodegenerative disease. The main component of senile plaques is ß-amyloid. The aim of the study. To study the expression of ß-amyloid in cells of cerebral endothelium of the hippocampus in experimental Alzheimer’s disease in vivo, to evaluate the production of ß-amyloid precursor protein (APP) upon RAGE and CD147 modulation in the cerebral vascular endothelium as part of the BBB model in vitro. Methods. Male mice of lines the B6SLJ-Tg(APPSwFlLon, PSEN1 * M146L * L286V) 6799Vas (genetic model of Alzheimer’s disease) and C57BL / 6 (control group) at the age of 9 months. Male mice of the line the C57BL / 6 at the age of 4 months, which were introduced ß-amyloid for modeling Alzheimer’s disease, sham-operated animals were used as a control. The expression of ß-amyloid in the hippocampus was studied by immunohistochemistry. Quantitative analysis of APP gene expression in vitro was performed by PCR. Results. The expression of ß-amyloid in the endothelium of the hippocampus was significantly (р<0.001) increased both in animals with ß-amyloid administration compared to the group of sham-operated animals, and in animals with a genetic model of Alzheimer’s disease compared to the control group (р<0.0001). It was found that blocking the expression of RAGE reduces the production of APP, while the suppression of the expression of CD147 induces this process. However, the ligands of the RAGE and CD147 receptors - Ab1-42 and cyclophilin A, respectively, show the opposite effect. Conclusion. Alzheimer’s disease is accompanied by an increase in the level of ß-amyloid in the endothelium of the hippocampus, which indicates the activation of APP processing with the generation of neurotoxic ß-amyloid. This causes destructive changes in the endothelium, contributing to an increase in BBB permeability and disease progression. Exposure to RAGE and CD147 chemical modulators can affect APP production. This makes it possible to correct the negative course of the disease.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):26-33
pages 26-33 views

Forecasting the development of acute pancreatitis based on molecular genetic study

Imaeva A.K., Gallyamova L.F., Mustafin T.I., Nurgaleyeva A.K., Khusnutdinova E.K.

Abstract

Introduction. Molecular genetic research methods suggest the development of certain forms of pancreatitis and its complications. Aim of the study. Identification of risk factors for the development of acute forms of pancreatitis based on molecular genetic studies, taking into account territorial, gender, and nationality. Material and methods. The most characteristic gene mutations in the loci responsible for the development of pathology in the pancreas were studied. For this, a molecular genetic analysis of DNA samples in patients with acute pancreatitis was carried out. The polymorphisms of the ADH1B (Arg47His), ALDH2 (Glu487Lys), PRSS1 (Arg122His), CFTR (Phe508del), and SPINK1 (Asn34Ser) genes were studied. Results. Analysis of these mutations in polymorphic variants of the SPINK1 and PRSS1 genes did not reveal significant differences for the development of acute pancreatitis in the group of patients with acute pancreatitis (AP) and healthy individuals. Analysis of the polymorphic variant Arg47His of the ADH1B gene revealed ethnic differences among patients with acute pancreatitis. Among residents of the Republic of Bashkortostan, the presence of the Arg/Arg genotype in Russians is a factor of increased risk of developing the disease. The presence of the Lys allele and the Glu/Lys genotype in the ALDH2 gene in female patients determines a tendency towards an increased risk of developing acute pancreatitis in residents of this region. The detection of the Phe508del mutation in the CFTR gene is associated with the development of destructive forms of pancreatitis. Conclusion. Identification of a risk group in a large region by identifying the indicated mutations in the ADH1B, ALDH2, and CFTR genes is important for preventing the development of acute, including destructive forms of pancreatitis.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):34-40
pages 34-40 views

Phase I clinical study of a new radiopharmaceutical based on recombinant target molecules DARPin9_29 labeled with technetium-99m for radionuclide diagnosis of the Her2/neu-positive breast cancer

Bragina O.D., Chernov V.I., Larkina M.S., Stasyuk E.S., Zelchan R.V., Medvedeva A.A., Garbukov E.Y., Vernadskyi R.Y., Deev S.M., Tolmachev V.M.

Abstract

Introduction. The main attention of researchers is paid to the study of one of the members of the EGFfamily - the receptor of epidermal growth factor 2 (Her2/neu), the overexpression of which is detected in 15-20% of cases of invasive breast cancer and had an unfavorable prognosis and an aggressive process. In recent years, alternative scaffold proteins are used for the targeted radionuclide imaging. Molecules of DARPin (Design Ankyrin Repeat Protein) are one of the representatives of scaffolds. The aim of the study. Assessment of the clinical use of a new radiopharmaceutical 99mTc-DARPin9_29 for the diagnosis of breast cancer with overexpression of Her2/neu in humans. Methods. The study included 12 breast cancer patients (T1-4N0-2M0): in 6 patients, Her2/neu overexpression was noted, in 6 patients - not detected. At the preclinical stage, all patients underwent morphological and immunohistochemical studies of the primary tumor biopsy material. 99mTc-DARPin9_29 was injected intravenously before therapy, WholeBody scintigraphy and SPECT were performed 2, 4, 6, and 24 hours after injection. Results. The distribution of radiopharmaceuticals in organs revealed the greatest accumulation in the liver and kidneys, adrenal glands, and spleen. The half-life elimination from blood was 2.51 hours. In studying tumor/background index, values of the studied parameter in patients with overexpression of Her2 receptors were revealed to be more than by 2.5 times higher than the values in the subgroup of patients with negative expression of this marker. Conclusion. The radiopharmaceutical 99mTc-DARPin9_29 may be considered as a new additional method for Her2-positive breast tumors diagnosis.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):41-48
pages 41-48 views

Protective effect of coded L-amino acids in cytostatic presence on the development of organotypic culture of tissues of different genesis

Chalisova N.I., Ryzhak G.A., Ivko O.M., Zalomaeva E.S., Ivanova P.N.

Abstract

Introduction. The cytostatics, inhibiting the cellular proliferation, are using in clinic for the inhibition of tumor development in patients. However, the adverse events can occur because of the damage of health cells of other tissues. A delay or decrease of these effects is an actual medicine task. Purpose of the study was the investigation of effects of coded L-amino acids on a decrease of cytostatic inhibiting effects in the culture of tissues of different genesis. These amino acids are not only the structural elements of the proteins, but can participate in the regulation of the genes, controlling the cellular cycle. Methods of organotypic culture of tissues of brain cortex, muscle, bladder of Wistar line rats in presence of cytostatic cyclophosphane (CP) and also of L-amino acids were used. The combined effect of CP and L-amino acids, stimulating the cellular regeneration, the cytostatic inhibiting effect on the cellular proliferation in the tissues of different genesis decreased by 10-43%. Conclusion. The data obtained about protective effect of coded hydrophile L-amino acids by cytostatic effect creates the base for development of medications for the delay of adverse effects related to the chemotherapy.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):49-53
pages 49-53 views

Features of local expression of mRNA, IL-1 ß, IL-18, CCL2/MCP-1 in modeling pigment epithelium atrophy and retinal degeneration in the experiment on rabbits

Neroev V.V., Balatskaya N.V., Svetlova E.V., Neroeva N.V., Ryabina M.V., Karmokova A.G., Losanova O.A., Chernomorets I.Y., Ilyukhin P.A.

Abstract

Introduction. Degenerative retinal diseases are considered as the leading cause of blindness and low vision worldwide. The last studies have provided convincing evidence of the involvement of immunological factors in the development and progression of the disease. Meanwhile the immunopathogenesis of the wet form of AMD has been studied more fully than the atrophic one. The aim of the study. Study of local expression of mRNA of inflammatory cytokines IL-1ß, IL-18, CCL2/MCP-1 in a model of RPE atrophy. Material and methods. The material for the study was samples of the retinal-RPE-choroid (TC) tissue complex isolated at various times from the enucleated rabbits’ eyes with previously created RPE atrophy by subretinal injection of 0,9% sodium chloride solution. Optical coherence tomography (OCT) and autofluorescence (AF) study using HeidelbergSpectralis ™ SD-OCT were performed. Local expression of cytokines was determined by RT-PCR. Results. A single subretinal injection of 0.01 ml of 0.9% sodium chloride solution was found to be associated with multidirectional changes in the expression of mRNA of the IL-1ß, IL-18, MCP-1/CCL2genes relative to the norm. Three types of the retinal response, formed during the development of atrophic changes and determined by the degree of local mRNA expression of cytokine genes, were characterized. No correlation was found between the magnitude of local mRNA expression to the stimulus inducing atrophy and the size of the atrophic retinal lesion. Conclusion. Obtained data can be helpful in the research of RPE atrophy and in the stem cells treatment.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):54-62
pages 54-62 views

In memory of Natalia Nikolaevna Belushkina

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Molekulyarnaya Meditsina (Molecular medicine). 2021;19(2):63-63
pages 63-63 views

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