Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Gumenyuk LN, Bordyugov MD, Sarchuk EV, Knyazeva SV, Zastavskii VA, Krickaya DV, Saitibragimova SE, Kurtvelieva AI

Currently, researchers show considerable interest in the link between gut microbiota and idiopathic recurrent miscarriage (IRM). This study aimed to analyze taxonomic changes of gut microbiota and assess its relationship with plasma levels of cortisol, melatonin, TNFa and IL17 in women with IRM. We invited 55 women with IRM and 60 women with normal pregnancy, studied their gut microbiota, and registered serum concentrations of cortisol, melatonin, TNFa and IL17. Women with IRM had changed gut microbiota: significantly decreased — diversity (Chao1 p = 0.014), significantly decreased abundance of Bifidobacterium (p < 0.001), Lachnospira (p = 0.032), Roseburia (p = 0.003), Coprococcus (p = 0.012), and significantly increased abundance of Ruminococcus (p < 0.001) and Klebsiella (p = 0.002). We have shown a statistically significant relationship between cortisol level and abundance of Lachnospira (r = –0.51; p = 0.002), melatonin level and abundance of Coprococcus (r = –0.49; p = 0.012), and identified connections between TNF and IL17 concentrations and Chao1 index (r = –0.51; p = 0.002, r = –0.54; p = 0.001, respectively), TNF concentration and abundance of Ruminococcus (r = 0.51; p = 0.002), IL17 concentration and abundance of Bifidobacterium (r = –0.52; p = 0.001). Modulation of gut microbiota may have preventive and therapeutic effects in women with IRM.

Received: 2024-01-04

Published online: 2024-02-21

DOI: 10.24075/brsmu.2024.004

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VIEWS 208

Mamedov IS, Zolkina IV, Sukhorukov VS, Krapivkin AI

Thorough investigation of metabolome by mass spectrometry is of great importance for personalized and preventive medicine. It is only timely laboratory diagnosis involving the use of high-tech chromatographic analysis methods that can help identify the patients with disorders of amino acid and acylcarnitine metabolism. The study was aimed to determine the efficacy of conventional and additional markers of metabolic disorders of amino acids and acylcarnitines detected by chromatography–mass spectrometry for the diagnosis of congenital metabolic disorders in children, as well as to create specific panels of the most effective indicators and determine the potential diagnostic efficacy of indentification of the relationships between the levels of amino acids and acylcarnitines in pediatric patients with congenital metabolic disorders. We assessed amino acid and acylcarnitine profiles in blood spots by high-performance liquid chromatography–tandem mass spectrometry in patients aged 6 months to 16 years (48 boys and 32 girls) with suspected aminoacidopathy and organic aciduria/acidemia. The comparison group consisted of 35 children with suspected peroxisomal metabolic disorders, the control group included 40 generally healthy children of various age groups. The data obtained were used to conduct the analysis of correlations between the groups of markers. Strong correlation was revealed for the levels of metabolically most closely related compounds (r < 0.8, р < 0.001). However, a similar relationship between metabolically not closely related compounds (correlation coefficient 0.45–0.73 (р < 0.001)) was revealed for some groups of compounds. Thus, the acylcarnitine profile can be proposed as an additional potential marker to be used in cases of borderline phenylalanine levels, and the sum of normalized acylcarnitine levels (С12+С16) can be a potential secondary marker of phenylketonuria.

Received: 2024-01-11

Published online: 2024-02-15

DOI: 10.24075/brsmu.2024.003

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VIEWS 231

Barykin AD, Chepurnykh TV, Osipova ZM

The deep learning technologies have become the driver of the revolutionary changes in scientific research in various fields. The AlphaFold-2 neural network software development that has solved the semicentennial problem of 3D protein structure prediction based on primary amino acid sequence is the most obvious example of using such technologies in structural biology and biomedicine. The use of deep learning methods for the prediction of protein–ligand interactions can considerably simplify predicting, speed up the development of new effective pharmaceuticals and change the concept of drug design.

Received: 2023-12-06

Published online: 2024-02-08

DOI: 10.24075/brsmu.2024.002

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VIEWS 255

Yurchenko DA, Markova ZhG, Minzhenkova ME, Vorontsova EO, Shilova NV

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be identified unambiguously by standard cytogenetic methods. A comprehensive approach involving the use of molecular cytogenetic methods is required for the more thorough morphological assessment of such chromosomes, as well as for the development of strategy for genetic counseling of the patients being the sSMC carriers. It is widely accepted that the development of abnormal phenotype by the patients having sSMC in their karyotype is associated with the presence of euchromatic region material in the marker chromosome. Therefore, it results from the presence of relatively large DNA copy number variations (CNVs) in the form of duplication, triplication, and more increased copy numbers; which are localized in the pericentromeric region of the appropriate chromosome. Pericentromeric CNVs can be involved in the chromosome imbalance in asymptomatic carriers of sSMC as well, however, the boundaries of such imbalance have not been clearly identified. The study was aimed to acquire additional information about the genomic topology of the DNA regions insensitive to the genes copy number increase. FISH analysis with commercial and homemade DNA probes was performed in 18 carriers of sSMC 15 and 22 having no clinically significant phenotypic abnormalities. The molecular cytogenetic testing showed that pericentromeric euchromatic regions sized 1.2 Mb and 714 kb, respectively, were found in 33% of cases (6 out of 18). We assume that these regions comprise no potentially dosage-sensitive genes.

Received: 2023-10-23

Published online: 2024-01-31

DOI: 10.24075/brsmu.2024.001

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VIEWS 223

Zakharova MV, Zagoskin AA, Ivanov RA, Nagornykh MO

Technologies underlying the production of synthetic mRNAs in vitro have significantly expanded the possibilities for research and therapeutic use of this class of molecules. The flagship application area has been the niche of mRNA vaccines, but this class of therapeutic molecules has the potential to be applied in a much broader range of situations. The process of in vitro production of artificial RNA molecules is based on an enzymatic synthesis reaction, one of the components of which is a ribonuclease inhibitor. This protein protects synthesized RNA from attacks by ribonucleases and prevents degradation of the molecules, which is critically important for RNA. Eukaryotic ribonuclease inhibitor synthesized as a recombinant protein in the cells of E. coli bacteria is the most common choice. However, the structure of this protein makes it a difficult product to make in bacteria. This study aimed to test the production of a recombinant ribonuclease inhibitor in various strains of E. coli, and to show the effect that helper polypeptides and cellular chaperones have on this process. Using genetic engineering approaches, we constructed plasmids, from which chimeric ribonuclease inhibitor molecules and helper polypeptides were produced. The influence of various components on solubility of the target recombinant protein was assessed with the help of densitometry, to which we have subjected products of the PAGE electrophoresis. It was determined that combinations of a vector with a strong promoter for the expression of the RNH1 ribonuclease inhibitor gene and helper polypeptides MBP and TIG against the background of increased expression of cellular chaperones dnaK, dnaJ, grpE give the target product yield of 45 mg/l and 60 mg/l, respectively. The selected conditions allow large-scale production of this protein for further use in in vitro RNA synthesis in the context of production of medicines.

Received: 2023-11-16

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.058

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VIEWS 320

Vladimirsky GM, Zhuravleva MA, Dashieva AE, Korneeva IE, Nazarenko TA

Currently, in vitro fertilization (IVF) with embryo transfer is the main method of treatment of all forms of infertility, but successful cases ending in pregnancy still account for only a third of all cycles performed. It is necessary to take into account many parameters and investigate the connections between them in order to properly evaluate the results of IVF. Over the past decades, a number of IVF prediction models have been developed with the aim at assessing the outcomes in individual cases, but, given the generally poor prognostic capacity, only a few of them have proven to be clinically significant. This study aimed to create nonlinear IVF outcomes prediction models and identify the most significant factors affecting the said outcomes. Using a database containing information on more than 700 indicators of 7004 women aged 18 to 45 years who participated in the IVF program in Russia from 2010 to 2020, we trained a random forest model that predicted pregnancy in the IVF cycle with ROC-AUC = 0.69. This paper describes 20 most successful predictors of the resulting model and interprets their contribution to the prognosis. Of these, body mass index (BMI) and the number of received and fertilized oocytes have been covered in the scientific literature previously as predictors of IVF outcomes, but other parameters, such as anamnestic data, previous participation in an IVF program (number of cases and their results), as well as serum concentration of AMH, rarely appear in foreign prognostic models.

Received: 2023-11-24

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.057

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VIEWS 290

Radaeva OA, Simbirtsev AS, Kostina YuA, Iskandiarova MS, Negodnova EV, Mashnina SV, Yeremeev VV, Krasnoglazova KA, Babushkin IO

In spite of a vast number of trials devoted to quantitative characteristics of the cytokine profile in patients with various diseases, no exact reference intervals are presented. It is just as important that there is a limited number of trials analyzing circadian rhythms of cytokine synthesis in patients with arterial hypertension. The purpose of the work was to analyze the characteristics of circadian rhythms of cytokines (IL18, IL18 BP, LIF, sLIFr, M-CSF, MCSFR) in patients with Grade II essential arterial hypertension, and to detect pathogenetically significant characteristics developed following Covid-19. Blood samples were taken at 7.00–8.00, 12.00–13.00, 19.00–20.00.00, 00.00–1.00 to determine the levels of IL18, IL18 BP, LIF, sLIFr, M-CSF, MCSFR in 18 patients (56 (95% CI (54–69) years) with essential arterial hypertension (EAH) within three days prior to and following Covid-19. For this, the immunoenzyme method was used. The obtained data demonstrated altered circadian expression of cytokines in the peripheral blood of patients with essential hypertension depending on whether they have EAH or not, and their additional distortion following Covid-19, which is stable in the majority of cases. It is preserved for six months as low IL18 BP (р < 0.001), and twofold increase of sLIFr and MCSF (р < 0,001) at 18.00. A significant association is determined between the circadian rhythms of sLIFr and altered systolic BP resulting in the abnormal rhythm with BP rise at night (night peaker) in patients with EAH following COVID-19. The obtained fundamental data offer prospects for new research of immunopathogenesis following COVID-19 in patients with hypertension taking into account circadian rhythms of cytokines in the blood.

Received: 2023-11-29

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.056

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VIEWS 290

Macular rupture is among major vitreoretinal disorders resulting in significant visual function decline. In recent years, the use of platelet-rich autoplasma in the macular rupture surgery is considered to be promising. However, despite high rate of macular rupture closure (78–96%), the development of new technology for foveal microarchitectonics restoration and visual function improvement currently remains a pressing issue. The study was aimed to develop a new foveal reconstruction technique for macular rupture involving the use of autologous conditioned plasma. The reported study involved 9 patients (10 eyes) with idiopathic macular hole, who underwent standard three-port 27G vitrectomy involving the use of autologous conditioned plasma in accordance with the technique developed. The proposed technique makes it possible to achieve good clinical and functional surgical treatment outcome and ensures optimal and more manageable reconstruction of foveal microarchitectonics.

Received: 2023-12-04

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.055

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VIEWS 312