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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Nazarov VD, Cherebillo CC, Lapin SV, Sidorenko DV, Devyatkina YA, Musonova AC, Petrova TV, Nikiforova AI, Ivanova AV

Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive skeletal muscular weakness and atrophy. The newborn screening for spinal muscular atrophy should define all molecular forms of SMA. The aim of this study is to compare a PCR-based test for detection of homozygous SMN1 loss with multiple ligation probe amplification (MPLA) in patients with spinal muscular atrophy and other numerical changes of the SMN1 gene. PCR-based test was used to detect exon 7 of SMN1 gene homozygous loss. The study included 341 samples of patients with clinical suspicion of SMA from Biobank of Centre of Molecular Medicine of Pavlov State Medical University (Saint-Petersburg, Russia). Group 1 included 206 whole blood samples and Group 2 included 135 dried blood spot (DBS) samples. Copy number of the SMN1 and SMN2 genes had been evaluated with MLPA as a reference method. The results showed that kit was able to detect homozygous SMN1 loss in all samples from group 1 and 2 (Group 1: n = 67; 33%; Group 2: n = 19; 14%). At the same time in all samples with 1–3 copies of the SMN1 gene, the results of the kit were negative for homozygous loss of SMN1 gene (Group 1: n = 139; 67%; Group 2: n = 116; 86%). Kit showed high effectiveness in the detection of homozygous loss SMN1 gene. The kit detects all possible molecular forms of homozygous SMN1 gene loss in both DNA samples extracted from the whole blood and DBS.

Received: 2023-05-30

Published online: 2023-06-30

DOI: 10.24075/brsmu.2023.025

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VIEWS 2330

Vasileva OO, Tereschenko VP, Krapivin BN, Muslimov AR, Kukushkin IS, Pateev II, Rybtsov SA, Ivanov RA, Reshetnikov VV

Development of the new tuberculosis vaccines that would be effective in adults is an urgent task: worldwide, the annual death toll of this disease exceeds 1.5 million. In the recent decades, the matter has been addressed in numerous studies, but none has yielded an effective vaccine so far. There are many factors to resistance against tuberculosis; this study focuses on the T-cell response, a mechanism that enables elimination of intracellular pathogens, such as M. tuberculosis. We aimed to develop an mRNA vaccine capable of triggering a pronounced T-cell response to the M. tuberculosis antigens. The in silico analysis allowed us to select epitopes of the M. tuberculosis secreted protein ESAT6 (Rv3875) and design a multi-epitope mRNA vaccine thereon. We assessed the intensity of T-cell response in mice immunized with mRNA vaccines that encode a full-length or multi-epitope antigen. The results of this study in mice show that immunization with a multi-epitope mRNA vaccine produces twice as many IFNγ-secreting splenocytes in response to specific stimulation than immunization with an mRNA vaccine encoding the full-length protein. Thus, the developed multi-epitope mRNA vaccine can be an effective M. tuberculosis prevention agent the mode of action of which involves formation of a pronounced T-cell response.

Received: 2023-04-24

Published online: 2023-06-29

DOI: 10.24075/brsmu.2023.021

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VIEWS 3049

Batyrova ZK, Bolshakova AS, Kumykova ZKh, Kruglyak DA, Uvarova EV, Chuprynin VD, Mamedova FSh, Sadelov IO, Trofimov DYu

Two forms of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome are recognized: isolated uterovaginal agenesis and associated with extragenital malformations, including several well-recognized syndromes. Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant condition characterized by facial dysmorphism, ectodermal and skeletal features. TRPS comprises TRPSI (caused by a heterozygous pathogenic variant in TRPS1), TRPSII (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). Genital anomalies occur particularly in TRPSII. We present a case of rare combination TRPSII with MRKH syndrome. Delayed diagnosis resulted to prolonged pain syndrome and repeated surgery. Recognition of genital anomalies in TRPS allows timely referral diagnosis and appropriate care by paediatrician and adolescent gynaecologists.

Received: 2023-06-17

Published online: 2023-06-27

DOI: 10.24075/brsmu.2023.022

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VIEWS 1933

Guselnikova VV, Razenkova VA, Sufieva DA, Korzhevskii DE

Arterial hypertension is one of the most significant medical and social problems, being widespread and associated with the risk of renal failure, cardiovascular and cerebrovascular complications. The aim was to investigate the morphofunctional state of microglia in different regions of the rat brain in the setting of arterial hypertension. Brain samples from spontaneously hypertensive SHR rats aged 3–8 months (n = 4) were used as study material. Normotensive WKY rats of the same age (n = 3) were used as the control group. The work was performed using immunohistochemical analysis and confocal laser microscopy. During the quantitative analysis, we were seeking to determine the number of microgliocyte bodies and the area occupied by the bodies and processes of these cells per 1 mm2 of the nervous tissue. An immunohistochemical reaction for calcium-binding protein Iba1 revealed that in rats with arterial hypertension, microglia in the cerebral cortex, striatum, subcortical white matter and subfornical organ showed morphological signs of activation: increased body size and thickening of the processes of these cells. The strongest activation is demonstrated by microglia of the subfornical organ, which is in a preactivated state in normotensive rats. The performed statistical analysis revealed a trend towards an increase in the amount of microglia in the brain in SHR rats compared to animals in the control group. The Iba1/CD68 double immunofluorescence reaction showed no changes in the amount and/or distribution of lysosomal CD68 protein in spontaneously hypertensive rats compared to control group. The results obtained indicate chronic activation of microglia in the brain of spontaneously hypertensive rats. Activation of microglia in this case is not accompanied by an increase in the phagocytic activity of these cells.

Received: 2023-06-05

Published online: 2023-06-27

DOI: 10.24075/brsmu.2023.024

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VIEWS 1983

Gantsgorn EV, Denisenko OV, Osipenko YaO, Kalmykova DA, Ivanov AV, Gerasyuta SS, Bulguryan GA, Ivanova MH, Saakyan DA

Type 1 diabetes mellitus is a condition caused by autoimmune damage to insulin–producing beta cells of the pancreatic islets, leading to endogenous insulin deficiency. Despite the sufficient knowledge of the disease and the availability of clinical recommendations for substitution therapy, the number of patients with this pathology is growing worldwide. At the same time, their cohort is very heterogeneous, including amid different etiology, concomitant genetic background, variations in the manifestation of the disease and severity. In this regard, traditional ideas about type 1 diabetes mellitus are being questioned, which requires special attention when managing patients with a clinical picture of the disease that differs from the traditional one. The article presents a clinical case of type 1 diabetes mellitus in a young patient, which demonstrates the importance of a personalized approach to the diagnosis and treatment of diabetic patients with a "non-classical" history.

Received: 2023-05-13

Published online: 2023-06-26

DOI: 10.24075/brsmu.2023.023

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VIEWS 2064

Koniaeva AD, Varakuta EYu, Leiman AE, Rafiev DO, Bolbasov EN, Stankevich KS

Wound defects of the oral mucosa are a common pathology the treatment of which often involves synthetic membranes. Development of varieties of such membranes is an ongoing process. This study aimed to register morphological features of the oral mucosa regeneration process in the presence of one of the varieties, the polymer piezoelectric membranes. The study involved 45 Wistar rats divided into 3 groups: 1) animals with an open wound defect; 2) animals with a wound defect covered with a copper-coated polymer membrane; 3) intact animals. The samples for morphometric study were collected on the 3rd, 7th and 12th days. On the 3rd day, rats of group 1 had the specific area of granulation tissue 1.4 times greater than that in group 2 (p = 0.033). In group 1 rats, endotheliocytes expressed more VEGF than in the animals of group 2. In group 2, the defect was ultimately completely covered with the epithelial layer, which was not the case in group 1. On the 7th day, the epithelium in rats of group 2 was twice as thick as the layer registered in group 1 (p = 0.019). Granulation tissue was replaced by loose fibrous connective tissue. In group 1, the specific area of inflammatory infiltration was greater than that of loose fibrous connective tissue, and the VEGF expression level was lower than in group 2. On the 12th day, the predominant tissue in group 2 was the loose fibrous connective tissue, the VEGF expression level equaled that of group 3, and peripheral nerves began to grow. In group 1, the specific area of dense fibrous tissue was 3.9 times greater than that in group 2 (p = 0.012), the epithelium had pathological changes and the VEGF expression was below control values. Thus, a polymer piezoelectric membrane had a positive effect on the post-wound restoration of the oral mucosa tissues.

Received: 2023-05-18

Published online: 2023-06-20

DOI: 10.24075/brsmu.2023.020

Comments 0

VIEWS 2392

Rogova LN, Lipov DS, Perfilova VN, Kustova MV, Mukhina AV, Churzin DA

Granulosa cells feed the oocyte during its maturation and protect it. Aberrant apoptosis in these cells is known to ultimately impair oogenesis. The current knowledge of how extragenital inflammation affects apoptosis in granulosa cells is incomprehensive, which is the root of an urgent problem connected to the spread of inflammatory diseases and the growing level of female infertility. This study aimed to assess the intensity of granulosa cell apoptosis in women with impaired reproductive function that suffer from chronic respiratory and/or digestive system diseases of inflammatory origin, and to identify the link, if any, between the studied factor and dysfunction of the reproductive system in the test group. The group included 60 women with a history of respiratory and/or digestive system inflammatory pathology that underwent IVF in 2021–2022. The women were donors of the granulosa cells from the follicular fluid collected through transvaginal puncture of preovulatory follicles. We studied the apoptosis process with the help of flow cytometry. For statistical analysis, we used the Fisher's F-test and the Kruskal–Wallis test. Twenty participants without extragenital pathology in their medical histories, the first subgroup, had the level of apoptosis in granulosa cells at 0.0088 ± 0.0062%, which is significantly lower than in twenty donors with a history of chronic inflammatory digestive system diseases, the second subgroup (granulosa cell apoptosis at 0.0140 ± 0.0099%, p = 0.015), and the subgroup of women suffering from inflammatory diseases of the respiratory system (granulosa cell apoptosis at 0.0650 ± 0.0391%, p = 0.033); the efficacy of IVF was higher in the first subgroup.

Received: 2023-05-12

Published online: 2023-06-17

DOI: 10.24075/brsmu.2023.019

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VIEWS 1973

Gumenyuk LN, Zemlyanaya IA, Rami A, Badula ES, Ismailov AR, Seroshtanov NA, Kokareva SS, Cheremisova AA, Kupreichyuk YuR

Today, the association of gut microbiota with external genital endometriosis (EGE) is of special scientific interest. The study was aimed to assess alterations of the gut microbiota taxonomic composition and explore their correlations with plasma levels of IL6, IL8 and TNFα at the species level in patients with EGE. The crosssectional comparative study involved 50 patients with EGE (index group) and 50 healthy women (control group). The changes in the gut microbiota taxonomic composition and plasma levels of IL6, IL8 and TNFα were assessed. A significant decrease in the abundance of such species, as Coprococcus catu (р = 0.009), Turicibacter sanguinis (р = 0.008) and Ruminococcus gnavus (р < 0.001), along with the increase in the abundance of Eubacterium ramulus (р = 0.040), Bacterioides dorei (р = 0.001), Prevotella divia (р = 0.008) and Shigella flexneri (р < 0.001) were found in the gut microbiota taxonomic composition in patients with EGE. Significant correlations between the IL6 levels and the abundance of Turicibacter sanguinis (r = –0.92; р = 0.001), IL8 levels and the abundance of Shigella flexneri (r = 0.72; р < 0.001), TNFα levels and the abundance of Prevotella divia (r = 0.77; р = 0.001) were revealed. The findings add to the available literature data on the features of gut microbiota alterations and their association with some inflammation biomarkers in individuals with EGE, which can justify further research in this area and probably open up new approaches to treatment of the disease.

Received: 2023-01-13

Published online: 2023-06-15

DOI: 10.24075/brsmu.2023.018

Comments 0

VIEWS 2230