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Vol 17, No 4 (2019)

Articles

OMICS technology: the role and significance for personalized medicine

Paltsev M.A., Chemezov A.S., Linkova N.S., Drobintseva A.O., Polyakova V.O., Belushkina N.N., Kvetnoy I.M.

Abstract

Personalized medicine implements new methods of molecular diagnostic for increasing the efficacy of the treatment of patients and the verification of the liability to diseases. Thus the search, development and applying modern methods and technologies of biomedicine and biophysics is the important goal of this innovation area of knowledge. The goal of the review is the analysis of the applicability of omics technology (genomic, proteomic, metabolomics, pharmacogenomics) in personalized medicine. There is the description of the genomic ability for analysis circulating tumor DNA by liquid biopsy, micro RNA investigation as a biomarker of the pathology of cardiomyocytes and endotheliocytes, violation offibrosis, angiogenesis, myocardial ischemia. There was described the data of proteomic application for creating of the oncomarkers panel and molecular markers of cardiovascular pathology. There is information about perspectives of metabolomics for the diagnosis of the gastro-intestine pathology. Pharmacogenomics proves to be an effective approach for predicting the side-effects of drugs in diabetic patients. Thus, omics technologies are the fundamental and practical base for personalized medicine investigation.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):3-8
pages 3-8 views

Dendritic cells in therapy of breast adenocarcinoma

Chernysheva A.A., Chekhonin I.V., Gurina O.I., Shepeleva I.I., Popova T.N.

Abstract

Dendritic cells (DC), as professional antigen-presenting cells with functional plasticity, are widely studied in preclinical and clinical research of vaccines against various types of malignant tumors. Some of the studies DС have proved their efficiency. However, all over the world, there is no officially approved DC vaccine for the treatment of breast cancer. Knowledge and understanding of fundamental functions of DC, as well as the development of methods enhancing the effect of such vaccines, may contribute to the progress in this direction. In this review, we consider the features of the main types of DC and their role in the pathogenesis of breast cancer. Also, we describe the mechanisms of antigen uptake, processing, and presentation. In addition, considerable attention is paid to the current research of DC-based treatment of breast adenocarcinoma as DC are studied both as monotherapy or in combination with other therapeutic strategies.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):9-16
pages 9-16 views

Comparative analysis of methods of mitochondrial replacement therapy

Glukhov A.I., Isagadzhiev A.M.

Abstract

Mitochondrial diseases are a group of inherited diseases characterized by the presence of defects in the mitochondrial mechanism of the patient. The distinguishing feature of such diseases is in transferring it via the maternal line to all the offspring. Various methods of mitochondrial replacement therapy are developed for the treatment of such diseases. Mitochondrial replacement therapy is a procedure which is used for the prevention of transferring such diseases via the maternal line to all descendants. There are several methods of this therapy. They are the following: pronuclear transfer, spindle transfer, polar body transfer 1 and 2. In this article, there are described modern used methods of mitochondrial replacement therapy. We should like to mention all the aspects of carrying out these procedures as well as complications and key features which must be taken into consideration when realizing them are also explained. We assessed the efficacy of these methods by comparing the data obtained by other researchers in the last 10 years. Having done such work we make a conclusion the most effective method of mitochondrial replacement therapy to be the polar body transfer 1. Besides it, we have revealed the spindle transfer to be also promising in spite of less prominent experimental results.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):17-21
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Brain metabolites analysis in patients with type 2 diabetes and cognitive impairement

Matveeva M.V., Samoilova Y.G., Zhukova N.G., Kudlai D.A.

Abstract

Introduction. Type 2 diabetes mellitus (DM) is a metabolic disease characterized by prolonged hyperglycemia, which can cause various complications. Some studies have reported on the relationship between changes in cerebral metabolism and glucose levels. The aim of the study. Assessment of the content of brain metabolites in patients with type 2 diabetes. Methods. The study was an observational, one-stage, one-time, selective. Objects - patients with type 2 diabetes aged 45-65 years. All subjects were sampled to determine fasting plasma glucose, glycated hemoglobin (HbA1c), and tau protein. To assess the variability of glycemia was assessed using continuous monitoring for 14 days. Neuropsychological testing was performed using the Montreal cognitive dysfunction scale (MoCA test). Neurochemical changes in the brain were studied using proton spectroscopy (1HMRS) and the analysis of the following metabolites: N-acetylaspartate (NAA), choline (Cho), creatine (Cr), creatine phosphate (Cr2). The main indicators that were determined during this study were fasting glucose levels, HbA1c, glycemic variability coefficients, tau protein levels, MoCA test results, and the content of brain metabolites in the hippocampus. Results. As a result, 48 patients with type 2 diabetes were examined. The level of tau protein in serum was increased in the presence of cognitive disorders and amounted to 44,6 pg/ml, its increase is associated with age, high HbA1c (r=0,211, p=0,034; r=0,342, p=0,006). Anincrease in glycemia variability coefficients is recorded. Patients with type 2 diabetes have cognitive impairment, the MoCA test was 20 points on average. There is an increase in NAA and Cho of the hippocampal region. It has been found that elevated NAA levels are found in patients with high tau protein content, and high HbA1c levels, glycemia lability index and average glucose value in patients with type 2 diabetes with a reduced Cr level in the hippocampus region. Conclusion. Type 2 diabetes occurs with cognitive impairment, changes in brain metabolism and increased tau protein. The model for predicting cognitive impairment according to 1HMRS in patients with type 2 diabetes is 79%
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):22-27
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Skeleton formation and polymorphism of androgen receptor gene in transsexual individuals

Solov’eva N.V., Makarova E.V., Vil’yanov V.B., Kremenitskaya S.A., Chausova S.V., Kichuk I.V., Shibalev D.V., Vasilyev V.A.

Abstract

Introduction. The androgen receptor (AR) gene MIGHR is known to be associated with transsexualism. Bone tissue is one of the target organs for androgens. Trochanteric index (TI) (ratio of height to the leg length) may indicate the organism androgenization level during puberty. It is interesting to identify the peculiarities of this process in the trans-person population. The aim of the study. To identify the connection between androgen receptor (AR) gene CAG-polymorphism and skeletal formation type in transgender persons.Methods. The study involved 262 patients above 18 years with the diagnosis of transsexualism (121 MtF, 141 FtM). Mental and sexual status; trochanteric index (TI); and genetic analysis (AR gene polymorphism) was estimated. Results. The average TI in the MtF group accounts for 1,93±0,03, which represents hypo-evolutive type of skeletal development. For FtM group TI was 2,01±0,04, that matches frontier between normal evolutive and hyper-evolutionary types. Differences in TI values in the MtF and FtM were significant (p=0,000). The MtF and FtM groups showed significant differences in the number of СAG repeats (p=0,000). A strong negative correlation was found between the TI value and number of CAG repeats in both groups (R=-0,24; p=0,000). Conclusion. TI is associated with polymorphism of AR. FtM population is characterized by a less number of CAG repeats in the AR gene compared to MtF, a higher TI, and a tendency toward a hyper-evolutionary type of the formation of the skeleton. The MtF population otherwise is characterized by a hypo-evolutive type of the formation of the skeleton.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):28-33
pages 28-33 views

The role and interaction of polymorphic variants of non-allelic genes KCNJ11, ADIPOQ, ITLN1, LEP, TCF7L2, PPARG in the increase in the risk of diabetes type 2 in Kyrgyz Republic

Isakova Z.T., Kipen V.N., Talaibekova E.T., Aldashev A.A., Aldasheva N.M., Bectursunov T.M., Mirrakhimov E.M.

Abstract

Aim. To study the intergenic interaction and estimate the contribution of polymorphic loci p.K23E (rs5219, KCNJ11), g.15661G>T (rs1501299, ADIPOQ), p.V109D (rs2274907, ITLN1), g.2453G>A (rs7799039, LEP), g.53341C>T (rs7903146, TCF7L2), and p.P12A (rs1801282, PPARG) in the gain of the risk of DM2 using bioinformatics method of multifactor dimensionality reduction (MDR). Material and methods. A study conducted by the «case-control», included 114 patients (61 male (53,5%), 53 females (46,5%)) with DM2 (main group) and 109 patients (61 male (56%), 48 females (44%)) without DM2 (control group). Genotyping was performed by the PCR-RFLP. Analysis of intergenic interactions bioinformatics was conducted by the method of multifactor dimensionality reduction (Multifactor Dimensionality Reduction, MDR). Results. Among studied polymorphic variants the largest contribution to the gain in the risk of DM2 in persons of Kyrgyz nationality is contributee by g.15661G>T (ADIPOQ), and p.K23E (KCNJ11). Genetic markers of the elevated risk of DM2 include: allele T (OR=1,68; 95% CI=[1,09-2,60], p=0,025), the heterozygous genotype GT (OR=1,79, 95% CI=[1,05-3,05], p=0,037) of the polymorphism g.15661G>T (ADIPOQ), and allele A of the polymorphism p.K23E (KCNJ11) - OR=1,62 (95% CI=[1,10-2,38], p=0,019). Polymorphic loci p.V109D (ITLN1), g.2453G>A (LEP), g.53341C>T (TCF7L2) and p.P12A (PPARG) in the progress of DM2 do not have a significant impact individually, but the implementation in phenotypic DM2 they can take place due to the effect of intergenic interactions. In the presence of a genetic profile «CC (g.53341C>T, TCF7L2) / AG (g.2453G>A, LEP) / AA (p.K23E, KCNJ11)» and «CT (g.5341C>T, TCF7L2) / AA (g.2453G>A, LEP) / AG (p.K23E, KCNJ11)» the risk of developing DM2 increases by 5-8 times. Conclusion. For persons of Kyrgyz nationality polymorphic loci p.K23E (KCNJ11) and g.15661G>T (ADIPOQ) are associated with the increased risk of DM2. The loci g.2453G>A (LEP), p.V109D (ITLN1), g.53341C>T (TCF7L2) and p.P12A (PPARG) can affect the phenotypic realization of DM2 in combination with pathogenetically significant genotypes of the genes KCNJ11 and ADIPOQ.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):34-44
pages 34-44 views

Polymorphism and synergism of the hemostasis system genes in pathogenesis of infective endocarditis

Maltseva N.V., Laputenko T.A., Smirnova A.S., Kan S.L.

Abstract

Introduction. The genetically determined tendency of patients to thrombosis may be one of the etiopathophysiological factors of the infective endocarditis (IE). Aim. А search for variants of genes and their combinations in the hemostatic system, the carriage of which affects the pathogenesis (risks and outcome) of IE. Material and methods. Genotyping of 66 IE patients (20 women and 46 men), including 33 men and 12 women with acute and 13 men and 8 women with subacute course of the disease, and 63 patients (30 women and 33 men) with sepsis on polymorphic loci rs1801133 methylenetetrahydrofolate reductase gene MTHFR (MTHFRAla222Val(C677T)), rs1800790 of the beta-fibrinogen gene FGB (FGB-455G-A), rs5918 of the beta-3 integrin, thrombocyte fibrinogen receptor gene ITGB3 (ITGB3Leu33Pro(T1565C)) was carried out by the allele-specific polymerase chain reaction method. Results. Monogenic and combined carriage of MTHFR222Val(677T), FGB-455-A, ITGB3Leu33(T1565) alleles is associated with an increased risk of the development and death in IE cases. Conclusion. Multiplex analysis of variants of the polymorphic loci of the hemostatic system genes should be included in the algorithm of genotyping in the diagnosis and treatment of IE patients.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):45-51
pages 45-51 views

Giant cell tumor of the sacrum: radiological and morphological characteristics

Stepanova Y.A., Gritskevich A.A., Kharazov A.F., Morozova M.V., Kalinin D.V., Karelskaya N.A., Varava A.B.

Abstract

Introduction. Giant cell tumors (GCT) of bones are benign tumors with the potential for the aggressive course and ability to metastasize. GCT accounts for approximately 5% of all primary bone tumors. Materials and methods. The clinical case of the patient L., 35 years old, with a giant cell tumor of the sacrum is presented. During the preoperative examination according to ultrasound, MSCT and MRI, the patient showed the destruction of the cortical sacrum along the internal contour; a large, extra organized in the form of a rounded shape with clear, uneven contours, cystic-solid structure proceeded from this zone. The lesion was hypervascular, with large lacunae filled with blood. The difficulties in the diagnosis of this lesion and the possibilities of surgical treatment are shown. Establishing diagnosis was possible only according to histological and immunohistochemical studies. Results and discussion. The histogenesis of GCT is still unknown and in the International Histological Classification of Bone Tumors is referred to as an independent rubric - tumors of unknown origin. The GCT tissue is represented by 3 cell lines: stromal fibroblast-like, mononuclear macrophages, giant multinucleated cells. Truly tumorous of them are only stromal fibroblast-like cells, the cells of other lines play an important role in the manifestation of the characteristic properties of GCT. Thus, histological examination reveals a complex of characteristic pathological changes in GCT, which, however, can be differently combined and have different severity even in within one large focus, which often makes differential histological diagnosis difficult, especially with a small unrepresentative histo- or cytobioptate. Therefore, it is necessary to perform an immunohistochemical study. Conclusion. Localization of GCT in the pelvis and in the sacrum is extremely rare. However, although only 6% of GCTs are found in the sacrum, these tumors are the second most common type of primary tumor of the sacrum. Due to the extremely rare occurrence of this tumor, despite the criteria for identifying them according to MSCT and MRI, which are quite clearly described in the literature, erroneous preoperative differentiation of this tumor is possible due to the lack of general surgeons, gynecologists and urologists in these departments, with a larger share the chances of such patients getting wary of detecting of GCT of the sacrum
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):52-61
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DBH gene polymorphism in psoriasis patients

Sakaniya L.R., Tretiakov A.V., Shevtsova A.A., Kokaeva Z.G., Rudko O.I., Soboleva A.G., Korsunskaya I.M., Klimov E.A., Sobolev V.V.

Abstract

Introduction. Psoriasis is a chronic inflammatory autoimmune disease with complex etiology including inheritable factors as well. Some scientists suggest psoriasis to be a systemic disease affecting not only skin. Thus, on the edge of dermatology and psychiatry, there is formed a new scientific field called psychodermatology, which highlights the nature of the link between skin diseases and mental disorders. The aim of the study is to evaluate the role of 3 polymorphic loci in the dopamine beta-hydroxylase (DBH) gene (rs141116007, rs2097629, and rs1611115) in the development of psoriasis. Methods. Genotypes were studied with PCR-RFLP method. Restriction products were separated in 2% agarose gene. Statistical analysis was performed in WinPepi and in APSampler software. Results. We discovered an association of rs1611115:T allele with psoriasis. This allele has a recessive model of inheritance - the presence of C allele reduces risk of psoriasis by 4 times. Complex genotype study revealed an association between rs1611115:TT genotype with psoriasis: p<0,001, OR=3,88. No significant associations were found between rs141116007 and rs2097629. Conclusion. Associated with psoriasis genotype rs1611115:TT is related to decreased DBH activity, increased dopamine concentration and decreased norepinephrine concentration. We suggest altered concentrations of these neuromediators to play a role in the development of psoriasis.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(4):62-65
pages 62-65 views

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