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Vol 18, No 5 (2020)

Articles

Blood system under COVID-19 infection: pathogenic mechanisms of disorders and perspectives of therapy

Martusevich A.K.

Abstract

The purpose of this review is a systematic analysis of data from clinical observations, international experience, and reviews related to the pathogenetic aspects of the impact of a new coronavirus infection on the blood system. Information was searched in MedLine, PubMed, and RSCI databases. A brief description of the etiological agent with a detailed analysis of the structure of this virus is given. The features and mechanisms of immunological shifts induced by SARS-CoV-2 infection are analyzed. Hematological and metabolic changes in the blood of COVID-19 patients are presented and described. The reaction of erythron to the development of a new coronavirus infection was evaluated from pathogenetic and clinical positions. In whole, the agent of a new coronavirus infection was shown in patients to have a multifaceted negative effect on the blood system, which is reflected in the dysfunction of the immune system (predominantly cellular) with the formation of a special syndrome termed as «cytokine storm», a hypercoagulable state until the development of disseminated intravascular coagulation, as well as reducing the absolute number of all formed elements of blood. Understanding the mechanisms of development of these shifts creates opportunities for delivering new technologies for targeted therapy.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):3-10
pages 3-10 views

Hyaluronic acid in the cell cycle of tumor cells

Khabarov V.N., Belushkina N.N., Paltsev M.A., Kvetnoy I.M.

Abstract

The review considers the role of hyaluronic acid (HA), primarily low-molecular-weight fractions of HA, in the regulation of the cell cycle of tumor cells. The formation of a pool of low-molecular weight HA molecules is due to the high activity of hyaluronidases, absolutely prerequisite for the development of a tumor in the case of intensive cell division. There was also a high level of HA in tumor cells due to the increased activity of hyaluronate synthases HAS1, 2, 3. HA, interacting with the CD44 receptor, alter the functional activity of cytokines, regulatory proteins, and gene groups. This contributes to the continuous proliferation of the tumor cells and strengthens the processes associated with cell invasion and migration. The formation of a complex of receptors around CD44 plays an important role in the continuous activation of the cycle responses in tumor cells. In most types of normal cells, the activity of CD44 receptor genes is suppressed by the p53 protein. The degeneration of a normal cell into a tumor cell is usually associated with deletions and mutations of the p53 protein gene, resulting in high activity of the CD44 receptor. In the case of the native p53 protein gene, activation of the CD44 receptor gene is carried out due to a high concentration of IL-6 cytokine, which activates and supports a cascade of CD44 gene activation responses. As a resulT., there is a constant activity of a number of major regulatory proteins: C-Myc, c-Ras, c-Src, K-Ras, AkT., ERK, β-catenin, STAT3, etc., characteristic of tumor cells.'
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):11-17
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Biofilms formation and degradation: molecular and cellular mechanisms

Khomyakova T.I., Tereshin M.N., Esipov R.S., Magomedova A.D., Kozlovskaya G.V., Kozlovsky Y.E., Khomyakov Y.N.

Abstract

Communities of microorganisms are a set of species that interact with each other and occupy the same niche where competitive or mutually beneficial relationships can occur. Biofilms are only one of many types of microbial communities, the study of which has become relevant in the last twenty years. A particular problem is the increase of antibiotic resistance of bacteria during their transition from a plankton lifestyle to a biofilm. The purpose of this review is to analyze current trends in the study of the mechanisms of biofilm formation, intercellular interaction in the formation of multicellular bacterial aggregates, primary adhesion, the relationship of bacteria in mature biofilms, the dispersion of them and distribution in the body. Data on the role of quorum sensing, G-proteins, and micro-RNA in the life cycle of biofilms are presented. The main components of the extracellular matrix are described at the molecular level, their production by microorganisms is presented. A separate chapter describes the results of the authors’ research on the development of effective probiotic bacteria capable to form biofilms on the walls of the colon mucosa. There is a proposed method for screening strains of potential probiotics as potential protectors and inhibitors of biofilm formation by competitive interaction with pathogens at the resulting adhesion sites.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):18-27
pages 18-27 views

Flash monitoring is a clinically effective method for achieving compensation for diabetes mellitus type 1

Samoilova Y.G., Koshmeleva M.V., Oleynik O.A., Filippova T.A., Tolmachev I.V., Kudlay D.A., Mutalimi V.E., Bolotova N.V.

Abstract

Introduction. Continuous glucose monitoring (CGM) is currently one of the most promising methods for controlling type 1 diabetes (T1D). Flash monitoring is the most relevant and promising direction in diabetology, which allows to monitor the level of glycemia an unlimited number of times and, as well as does not require calibration of the device. The aim of the study: to evaluate the clinical and metabolic effectiveness of flash monitoring of glycemia in patients with T1D. Methods. The study included 80 patients with T1D on various insulin therapy regimens. All patients were tested for glycated hemoglobin (HbA1c), flash glycemia monitoring, and quality of life assessment using the MOS SF 36 and PedsQl Diabetic module 3.2 questionnaires. Based on the glycemic charts were evaluated: the average level of glycemia (mmol/l), time of blood glucose above target value (%), time of glucose within target values (time in range), time of blood glucose below target values (%), frequency of Hypo - and hyperglycemia (episodes per week), the average daily dose of insulin (U/l). Results. HbA1c decreased by 1.6% (p<0.001) at the end of the study in the pump insulin therapy group. In patients of the basic bolus group HbA1c decreased by 0.6% and reached 8.9 % (p=0.028). When comparing the glycemic control indicators of the two groups, the average blood glucose level decreased in the pump insulin therapy group to 7.51+1.53 mmol/l, in the second group this indicator was 7.25+2.43 mmol /1 (p<0.001). When assessing the quality of life indicators, improvement was found in both the first and second groups. Conclusion. Continuous monitoring, including flash monitoring, is an effective method of monitoring and achieving glycemic goals in patients with T1D, and is also an optimal tool for improving the quality of life regardless of the insulin therapy regimen.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):28-35
pages 28-35 views

The association of RS75555045 and RS12904699 with sudden cardiac death

Ivanova A.A., Melnikova E.S., Gurazheva A.A., Malutina S.K., Rodina I.A., Khamovich O.V., Novoselov V.P., Maksimov V.N.

Abstract

Introduction. The single-nucleotide polymorphisms rs75555045 and rs12904699 were found in the own genome-wide allelotyping as possible new molecular genetic markers of sudden cardiac death (SCD). The results obtained in such studies require verification in the case-control studies using routine molecular genetic methods for eliminating false positive results. The aim of the study. Confirm the association of single nucleotide polymorphisms rs75555045 and rs12904699 with SCD. Methods. The SCD group (n=437, average age - 53,1±9,0 years, men - 73,5%, women - 26,5%) were formed from suddenly died individuals with pathological diagnoses «acute coronary insufficiency» and «acute circulatory failure». The control group formed of the MONICA and HAPIEE project participants alive at the time of the project (n=407, average age 53,3±9,0 years, men - 72,2%, women - 27,8%). DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was done by PCR-RFLP method. Results. No statistical significance was found in allele and genotype frequencies of rs75555045 between groups (p>0,05). In the SCD group the proportion of the AA genotype of rs12904699 is statistically significantly less (8,5%) than in the control group (13,8%) (OR=0,57, 95% CI: 0,36-0,89, p=0,014). In the subgroup of women died of SCD, the frequency of the GG genotype of rs12904699 was statistically significantly higher (61,1%) compared with the control group (46,8%) (OR=1,78, 95% CI 1,04-3,05, p=0,04). Conclusion. The association of rs75555045 with SCD has not been confirmed. rs12904699 associated with SCD: AA genotype is associated with a protective effect on SCD, GG genotype is associated with an increased risk of SCD in women.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):36-40
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Evaluation of the oxidative modification of blood plasma proteins and leukocytes in Alzheimer’s disease

Engalycheva M.G., Fomina M.A., Petrov D.S., Tazina T.V.

Abstract

Introduction. The development of neurodegeneration in Alzheimer’s disease is inextricably linked with oxidative stress, a marker of which is oxidative protein modification. In the tissues of the brain, cerebrospinal fluid and plasma in Alzheimer’s disease, an increase in carbonyl derivatives was recorded. The aim of the study to assess the level of spontaneous and induced oxidative modification of blood plasma proteins, polymorphic nuclear and mononuclear leukocytes in patients with Alzheimer’s disease; determine the number of primary and secondary markers of oxidative stress in the observation and comparison groups; to evaluate the value of the reserve-adaptive potential of plasma and leukocytes in the studied groups. Methods. Spectrophotometric determination of carbonyl derivatives of blood plasma proteins and fractionated leukocytes resulting from spontaneous and metal-catalyzed oxidation. Results. In the blood plasma of patients with Alzheimer’s disease, a significant predominance of secondary markers of oxidative damage to the protein is noted; the total level of products of spontaneous and induced oxidative modification of mononuclear leukocyte protein in patients with Alzheimer’s disease exceeds the similar level in the comparison group; significant depletion of the reserve-adaptation potential of both blood plasma and leukocytes in Alzheimer’s disease was revealed. Conclusion. The development of Alzheimer’s disease is associated with the accumulation of products of oxidative modification of proteins and the depletion of the reserve-adaptive potential of blood plasma and mononuclear white blood cells.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):41-45
pages 41-45 views

Prediction of the blastulation onset in one day behind embryos by the expression profile of small non-coding RNAs

Drapkina Y.S., Timofeeva A.V., Chagovets V.V., Makarova N.P., Frolova A.M., Kalinina E.A.

Abstract

Introduction. Successful embryonic development immediately after fertilization depends on the maternal messenger RNAs (mRNAs) destruction and zygotic genome transcription activation during maternal to zygotic transition (MZT). Key regulators of MZP are small noncoding RNAs (sncRNAs) - microRNAs and piwiRNAs. These molecules can be identified in embryo culture medium and used as a marker of embryo quality, blastulation ability, as well as its implantation potential. The aim this study. To analyze blastulation rate in embryos, which are one day behind in developmenT., according to microRNAs and piwiRNAs expression profile in their culture medium. Methods. The RT-PCR method was used for the quantitative analysis of microRNAs and piwiRNAs in 22 samples of embryo culture media obtained on day 4 after fertilization. Embryos included were one day behind in development and were at the 8-cells stage. The samples were divided into three groups according to morphological and functional characteristics of the embryos on day 6: group I - average/ excellent blastocysts (1 - 4AA, 1 - 4BB, 1 - 6BB, 1 - 3AA, 1 - 3BB), group II - poor quality blastocysts (3 - 4СС, 4 - 3СС, 1 - 2СС, 1 - 3ВС, and 1 - 4СВ) and group III - degraded embryos (7). Results. The culture media from embryos which degrade or become poor quality blastocysts on day 6 has almost the same level of microRNA let-7i-5p, but microRNA let-7i-5p expression level is statistically significantly higher in culture medium of the embryos which are capable to develop into average/excellent quality blastocyst. In culture media of embryos which develop into average/excellent quality blastocysT., the level of microRNA let-7b-5p and piwiRNA piR020401 is also statistically significantly higher then in culture media of degraded embryos and embryos which developed into bad quality blastocysts. Conclusion. The data obtained confirm the level of microRNA let-7b-5p, microRNA let-7i-5p and piwiRNA piR020401 to show embryo quality and development potential. Assessment of their expression level can be used for diagnostic and prognostic purposes in selecting the best quality embryo.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):46-52
pages 46-52 views

Comparative influence of hyaluronic acid on proliferation and apoptosis of skin cells in middle-aged women

Khabarov V.N., Kvetnoy I.M., Linkova N.S., Paltsev M.A.

Abstract

Introduction. Hyaluronic acid in combination with other biology active molecules and ions is an efficient drug for the function restoration and normalizing an external appearance of the skin during aging. However, the comparative investigation of hyaluronic acid biological activity in combination with other additives for bio arming with molecular methods using wasn’t applying yet. The aim of the study is to investigate the influence of hyaluronic acid in combination with various ions and other additives on skin cell proliferation and apoptosis in middle-aged women. Methods. Skin biopsies from middle-aged women were used after bio arming with applying hyaluronic acid drugs in combination with other biological active additives. The investigation of Ki67 and p53 proteins expression in skin cells was done by immunofluorescence confocal methods with quantitative analysis of the data by morphometric method. Results. Injections of hyaluronic acid without additives increased Ki67 proliferative protein expression in skin cells of middle-aged women by 2.9 times and didn’t’ changed on p53 proapoptosis protein expression. Injections of hyaluronic acid with magnesium and silicium ions increased Ki67 expression in skin cells of middle-aged women by 5.3 and 4.3 times and p53 expression - by 3.1 and 3.3 times. Conclusion. The most effective way of skin functional activity increasing is injections of hyaluronic acid for bio arming procedure in middle-aged women. Injections of hyaluronic acid with magnesium and silicon ions stimulate proliferation and apoptosis of skin cells and can be applying for young women’s skin revitalization.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):53-57
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Changes in protein expression of rat astrocytes co-cultured with C6 glioma cells

Silantyev A.S., Chekhonin I.V., Chernysheva A.A., Gurina O.I., Pavlova S.A., Pavlova G.V., Savelieva T.A., Loshhenov V.B., Chekhonin V.P.

Abstract

Introduction. Based on current literature data, it is possible to assume that when exposed to glioma cells astrocytes, may undergo a reactive transformation. These glioma-conditioned astrocytes might create a permissive environment for tumorigenesis. The aim of the study. To investigate the effects of glioma cells on astrocytes in co-culture. Methods. In terms of the current work, we conducted a pairwise comparison of protein levels between C6 glioma cells, native rat astrocytes, and glioma-conditioned rat astrocytes. The samples were prepared and analyzed with liquid chromatography-high-resolution mass spectrometry. Results. The analysis showed a significant difference in 162 proteins between glioma cells and native astrocytes, in 141 proteins between glioma cells and glioma-conditioned astrocytes and 70 proteins between glioma-conditioned and native astrocytes. Conclusion. The differences in protein levels between native and glioma-conditioned astrocytes show a high correlation with differences between glioma cells and native astrocytes.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(5):58-64
pages 58-64 views

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