Nina I Stavskaya, L. Ilchuk, YuD Okulova, MV Kubekina, EA Varlamova, YY Silaeva, A. Bruter
The CDK8 cyclin-dependent transcription-associated kinase and its less studied paralog, CDK19, regulate the expression of the dependant genes via several mechanisms. CDK8/19 can directly phosphorylate some transcription factors (ICN, STAT1), but at the same time these kinases being a component of the mediator complex regulate transcrition via interaction with chromatin in the promoter and enhancer regions of appropriate genes. Recently the papers have appeared showing that CDK8/19 has kinase-independent mechanisms of action through comparison of the effects of the kinase activity genetic inactivation and chemical inhibition. The study was aimed to generate transgenic mice capable of the induced and tissue-specific expression of the kinase-negative (showing no phosphorylation activity) form of CDK8, CDK8 (D173A), which could be later used to study the CDK8 kinase-independent mechanisms of action in vivo. We obtained four F0 transgenic animals by microinjection of linear DNA into the pronucleus, two of these animals became the ancestors of two distinct lines. The copy number of the integrated construct was measured for all F0 and the lines generated. This model may be used to study the kinase-independent properties of the CDK8/19 proteins.
{"title":"Transgenic mice for study of the CDK8/19 cyclin-dependent kinase kinase-independent mechanisms of action","authors":"Nina I Stavskaya, L. Ilchuk, YuD Okulova, MV Kubekina, EA Varlamova, YY Silaeva, A. Bruter","doi":"10.24075/brsmu.2022.066","DOIUrl":"https://doi.org/10.24075/brsmu.2022.066","url":null,"abstract":"The CDK8 cyclin-dependent transcription-associated kinase and its less studied paralog, CDK19, regulate the expression of the dependant genes via several mechanisms. CDK8/19 can directly phosphorylate some transcription factors (ICN, STAT1), but at the same time these kinases being a component of the mediator complex regulate transcrition via interaction with chromatin in the promoter and enhancer regions of appropriate genes. Recently the papers have appeared showing that CDK8/19 has kinase-independent mechanisms of action through comparison of the effects of the kinase activity genetic inactivation and chemical inhibition. The study was aimed to generate transgenic mice capable of the induced and tissue-specific expression of the kinase-negative (showing no phosphorylation activity) form of CDK8, CDK8 (D173A), which could be later used to study the CDK8 kinase-independent mechanisms of action in vivo. We obtained four F0 transgenic animals by microinjection of linear DNA into the pronucleus, two of these animals became the ancestors of two distinct lines. The copy number of the integrated construct was measured for all F0 and the lines generated. This model may be used to study the kinase-independent properties of the CDK8/19 proteins.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":"1 1","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41373548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Identification of the age-related features of interaction between the risk factors of microembolism can improve understanding of the mechanisms underlying the development of ischemic stroke (IS). The study was aimed to assess the effects of age and other risk factors of stroke on the biophysical characteristics of microembolic signals (MES) recorded during the ischemic stroke recovery period. Transcranial Doppler ultrasound (TCD) involving microembolus detection (MED) was performed in 515 people, the data of 28 patients having a history of ischemic stroke, among them 9 women (32%) and 19 men (68%) aged 33–78 (average age 58 ± 13 years), were included in the study. Using the mixed-effects linear model it was found that age and interaction between age and atrial fibrillation affected the power of MES. The increase in the power of the recorded MES with age is observed, that is especially evident in patients with atrial fibrillation (р < 0.0005). As for cardioembolic IS variant, the power and duration of MES turn out to be significantly higher in elderly patients (p < 0.0005). The power of MES gradually increases with age in patients with no atherosclerosis and gradually decreases in patients with atherosclerosis, while MES power in patients with atherosclerosis in general (all age groups) is significantly higher (р < 0.0005) than that observed in patients with no atherosclerosis.
{"title":"Correlation of microembolism risk factors with age in the ischemic stroke recovery period","authors":"E. Orlova, A. Berdalin, V. Lelyuk","doi":"10.24075/brsmu.2022.058","DOIUrl":"https://doi.org/10.24075/brsmu.2022.058","url":null,"abstract":"Identification of the age-related features of interaction between the risk factors of microembolism can improve understanding of the mechanisms underlying the development of ischemic stroke (IS). The study was aimed to assess the effects of age and other risk factors of stroke on the biophysical characteristics of microembolic signals (MES) recorded during the ischemic stroke recovery period. Transcranial Doppler ultrasound (TCD) involving microembolus detection (MED) was performed in 515 people, the data of 28 patients having a history of ischemic stroke, among them 9 women (32%) and 19 men (68%) aged 33–78 (average age 58 ± 13 years), were included in the study. Using the mixed-effects linear model it was found that age and interaction between age and atrial fibrillation affected the power of MES. The increase in the power of the recorded MES with age is observed, that is especially evident in patients with atrial fibrillation (р < 0.0005). As for cardioembolic IS variant, the power and duration of MES turn out to be significantly higher in elderly patients (p < 0.0005). The power of MES gradually increases with age in patients with no atherosclerosis and gradually decreases in patients with atherosclerosis, while MES power in patients with atherosclerosis in general (all age groups) is significantly higher (р < 0.0005) than that observed in patients with no atherosclerosis.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43928502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Chebotar, Y. Bocharova, AV Chaplin, T. Savinova, YuA Vasiliadis, N. Mayanskiy
The carbapenem-resistant strains of Pseudomonas aeruginosa are considered as the dangerous pathogens of critical priority. Deciphering the mechanisms underlying the development of carbopenem resistance is an urgent challenge faced by modern medical science. The study was aimed to describe the diversity and fixation of mutations associated with the development of carbapenem resistance during the P. aeruginosa adaptation to the increasing meropenem concentrations. The objects of the study were P. aeruginosa isolates obtained by growing the ATCC 27853 P. aeruginosa reference strain exposed to increasing concentrations of meropenem. The isolates were tested for meropenem susceptibility using E-tests (Epsilometer tests) and by the agar dilution method. Genomes of the isolates were sequenced in the MGISEQ-2000 whole-genome sequencer. The findings show that in experimental settings P. aeruginosa develops high meropenem resistance very quickly (in 6 days). Evolution of resistance is associated with cloning involving the emergence of multiple clones with various genotypes. Mutagenesis that involves 11 genes, including oprD, pbuE, nalD, nalC, spoT, mlaA, mexD, mexR, oprM, mraY, pbp3, provides the basis for cloning. Regardless of the levels of their meropenem resistance, some of the emerging clones do not progressively develop and are replaced by more successful clones.
{"title":"Mutational basis of Meropenem resistance in Pseudomonas aeruginosa","authors":"I. Chebotar, Y. Bocharova, AV Chaplin, T. Savinova, YuA Vasiliadis, N. Mayanskiy","doi":"10.24075/brsmu.2022.063","DOIUrl":"https://doi.org/10.24075/brsmu.2022.063","url":null,"abstract":"The carbapenem-resistant strains of Pseudomonas aeruginosa are considered as the dangerous pathogens of critical priority. Deciphering the mechanisms underlying the development of carbopenem resistance is an urgent challenge faced by modern medical science. The study was aimed to describe the diversity and fixation of mutations associated with the development of carbapenem resistance during the P. aeruginosa adaptation to the increasing meropenem concentrations. The objects of the study were P. aeruginosa isolates obtained by growing the ATCC 27853 P. aeruginosa reference strain exposed to increasing concentrations of meropenem. The isolates were tested for meropenem susceptibility using E-tests (Epsilometer tests) and by the agar dilution method. Genomes of the isolates were sequenced in the MGISEQ-2000 whole-genome sequencer. The findings show that in experimental settings P. aeruginosa develops high meropenem resistance very quickly (in 6 days). Evolution of resistance is associated with cloning involving the emergence of multiple clones with various genotypes. Mutagenesis that involves 11 genes, including oprD, pbuE, nalD, nalC, spoT, mlaA, mexD, mexR, oprM, mraY, pbp3, provides the basis for cloning. Regardless of the levels of their meropenem resistance, some of the emerging clones do not progressively develop and are replaced by more successful clones.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43050424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DS Bormotov, Mariya A. Shamraeva, AA Kuzin, EV Shamarina, Vasily A Eliferov, SV Silkin, EV Zhdanova, SI Pekov, I. Popov
The primary method of initial treatment of meningiomas is radical neurosurgical intervention. Various methods of intraoperative diagnostics currently in development aim to improve resection efficiency; we focus on methods based on molecular profiling using ambient ionization mass spectrometry. Such methods have been proven effective on various tumors, but the specifics of the molecular structure and the mechanical properties of meningiomas raise the question of applicability of protocols developed for other conditions for this particular task. The study aimed to compare the potential clinical use of three methods of ambient ionization in meningioma sample analysis: spray from tissue, inline cartridge extraction, and touch spherical sampler probe spray. To this end, lipid and metabolic profiles of meningioma tissues removed in the course of planned neurosurgical intervention have been analyzed. It is shown that in clinical practice, the lipid components of the molecular profile are best analyzed using the inline cartridge extraction method, distinguished by its ease of implementation and highest informational value. Analysis of oncometabolites with low molecular mass is optimally performed with the touch spherical sampler probe spray method, which scores high in both sensitivity and mass-spectrometric complex productivity.
{"title":"Ambient ms profiling of meningiomas: intraoperative oncometabolite-based monitoring","authors":"DS Bormotov, Mariya A. Shamraeva, AA Kuzin, EV Shamarina, Vasily A Eliferov, SV Silkin, EV Zhdanova, SI Pekov, I. Popov","doi":"10.24075/brsmu.2022.072","DOIUrl":"https://doi.org/10.24075/brsmu.2022.072","url":null,"abstract":"The primary method of initial treatment of meningiomas is radical neurosurgical intervention. Various methods of intraoperative diagnostics currently in development aim to improve resection efficiency; we focus on methods based on molecular profiling using ambient ionization mass spectrometry. Such methods have been proven effective on various tumors, but the specifics of the molecular structure and the mechanical properties of meningiomas raise the question of applicability of protocols developed for other conditions for this particular task. The study aimed to compare the potential clinical use of three methods of ambient ionization in meningioma sample analysis: spray from tissue, inline cartridge extraction, and touch spherical sampler probe spray. To this end, lipid and metabolic profiles of meningioma tissues removed in the course of planned neurosurgical intervention have been analyzed. It is shown that in clinical practice, the lipid components of the molecular profile are best analyzed using the inline cartridge extraction method, distinguished by its ease of implementation and highest informational value. Analysis of oncometabolites with low molecular mass is optimally performed with the touch spherical sampler probe spray method, which scores high in both sensitivity and mass-spectrometric complex productivity.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43666217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AA Traspov, MM Minashkin, S.Yu. Poyarkov, AG Komarov, I. Shtinova, G. Speshilov, IA Karbyshev, NV Pozdniakova, MA Godkov
Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18‒95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5; p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60; p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.
{"title":"The rs17713054 and rs1800629 polymorphisms of genes LZTFL1 and TNF are associated with COVID-19 severity","authors":"AA Traspov, MM Minashkin, S.Yu. Poyarkov, AG Komarov, I. Shtinova, G. Speshilov, IA Karbyshev, NV Pozdniakova, MA Godkov","doi":"10.24075/brsmu.2022.065","DOIUrl":"https://doi.org/10.24075/brsmu.2022.065","url":null,"abstract":"Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18‒95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5; p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60; p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44158096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RR Ibragimova, II Gilmanov, EA Lopukhova, I. Lakman, AR Bilyalov, T. Mukhamadeev, RV Kutluyarov, GM Idrisova
Age-related macular degeneration (AMD) is one of the main causes of loss of sight and hypovision in people over working age. Results of optical coherence tomography (OCT) are essential for diagnostics of the disease. Developing the recommendation system to analyze OCT images will reduce the time to process visual data and decrease the probability of errors while working as a doctor. The purpose of the study was to develop an algorithm of segmentation to analyze the results of macular OCT in patients with AMD. It allows to provide a correct prediction of an AMD stage based on the form of discovered pathologies. A program has been developed in the Python programming language using the Pytorch and TensorFlow libraries. Its quality was estimated using OCT macular images of 51 patients with early, intermediate, late AMD. A segmentation algorithm of OCT images was developed based on convolutional neural network. UNet network was selected as architecture of high-accuracy neural net. The neural net is trained on macular OCT images of 125 patients (197 eyes). The author algorithm displayed 98.1% of properly segmented areas on OCT images, which are the most essential for diagnostics and determination of an AMD stage. Weighted sensitivity and specificity of AMD stage classifier amounted to 83.8% and 84.9% respectively. The developed algorithm is promising as a recommendation system that implements the AMD classification based on data that promote taking decisions regarding the treatment strategy.
{"title":"Algorithm of segmentation of OCT macular images to analyze the results in patients with age-related macular degeneration","authors":"RR Ibragimova, II Gilmanov, EA Lopukhova, I. Lakman, AR Bilyalov, T. Mukhamadeev, RV Kutluyarov, GM Idrisova","doi":"10.24075/brsmu.2022.062","DOIUrl":"https://doi.org/10.24075/brsmu.2022.062","url":null,"abstract":"Age-related macular degeneration (AMD) is one of the main causes of loss of sight and hypovision in people over working age. Results of optical coherence tomography (OCT) are essential for diagnostics of the disease. Developing the recommendation system to analyze OCT images will reduce the time to process visual data and decrease the probability of errors while working as a doctor. The purpose of the study was to develop an algorithm of segmentation to analyze the results of macular OCT in patients with AMD. It allows to provide a correct prediction of an AMD stage based on the form of discovered pathologies. A program has been developed in the Python programming language using the Pytorch and TensorFlow libraries. Its quality was estimated using OCT macular images of 51 patients with early, intermediate, late AMD. A segmentation algorithm of OCT images was developed based on convolutional neural network. UNet network was selected as architecture of high-accuracy neural net. The neural net is trained on macular OCT images of 125 patients (197 eyes). The author algorithm displayed 98.1% of properly segmented areas on OCT images, which are the most essential for diagnostics and determination of an AMD stage. Weighted sensitivity and specificity of AMD stage classifier amounted to 83.8% and 84.9% respectively. The developed algorithm is promising as a recommendation system that implements the AMD classification based on data that promote taking decisions regarding the treatment strategy.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47530886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Timofeeva, IS Fedorov, A. Tarasova, KA Gorina, YuV Suhova, VA Gusar, TYu Ivanets
Preeclampsia (PE) occurs in 2–8% of pregnancies. It is one of the leading causes of maternal and perinatal morbidity and mortality. Today, there are no tests adopted by the practitioners that enable accurate prediction of early (weeks 20 through 34) or late (after week 34) onset of PE when the pregnancy is in its 11th to 14th week. This study aimed to evaluate the feasibility of using secretory clusterin quantification to predict early or late PE during the first trimester of pregnancy. The choice of this protein is determined, on the one hand, by the specificity of its expression for cytotrophoblast, syncytiotrophoblast, and extracellular trophoblast cells, and, on the other hand, by the proven negative effect of clusterin on the invasive properties of trophoblastic cells and gestational transformations of uterine vessels, which play a key role in the pathogenesis of PE. The study included 40 pregnant women aged 27–40 years who underwent a comprehensive screening examination in the first trimester of pregnancy. Western blotting revealed a significant increase in the level of secretory clusterin (40 kDa) in the blood serum of pregnant women in the case of PE compared to physiological pregnancy: in early-onset PE, a twofold increase in the level of clusterin in the vesicular and extravesicular fractions of blood serum (p = 0.03 and p = 0.004, respectively), with late-onset PE — a threefold increase only in the extravesicular fraction of blood serum (p = 0.002). According to logistic regression models, the level of secretory clusterin in the extravesicular fraction of blood serum of pregnant women in the first trimester has prognostic significance in assessing the likelihood of developing early-onset PE (AUC = 0.97, Se = 1, Sp = 0.875, cutoff = 0.3877) and late-onset PE ( AUC = 1, Se = 1, Sp = 1, cutoff = 0.5).
{"title":"Role of clusterin in predicting development of early- and late-onset preeclampsia in the first trimester of pregnancy","authors":"A. Timofeeva, IS Fedorov, A. Tarasova, KA Gorina, YuV Suhova, VA Gusar, TYu Ivanets","doi":"10.24075/brsmu.2022.061","DOIUrl":"https://doi.org/10.24075/brsmu.2022.061","url":null,"abstract":"Preeclampsia (PE) occurs in 2–8% of pregnancies. It is one of the leading causes of maternal and perinatal morbidity and mortality. Today, there are no tests adopted by the practitioners that enable accurate prediction of early (weeks 20 through 34) or late (after week 34) onset of PE when the pregnancy is in its 11th to 14th week. This study aimed to evaluate the feasibility of using secretory clusterin quantification to predict early or late PE during the first trimester of pregnancy. The choice of this protein is determined, on the one hand, by the specificity of its expression for cytotrophoblast, syncytiotrophoblast, and extracellular trophoblast cells, and, on the other hand, by the proven negative effect of clusterin on the invasive properties of trophoblastic cells and gestational transformations of uterine vessels, which play a key role in the pathogenesis of PE. The study included 40 pregnant women aged 27–40 years who underwent a comprehensive screening examination in the first trimester of pregnancy. Western blotting revealed a significant increase in the level of secretory clusterin (40 kDa) in the blood serum of pregnant women in the case of PE compared to physiological pregnancy: in early-onset PE, a twofold increase in the level of clusterin in the vesicular and extravesicular fractions of blood serum (p = 0.03 and p = 0.004, respectively), with late-onset PE — a threefold increase only in the extravesicular fraction of blood serum (p = 0.002). According to logistic regression models, the level of secretory clusterin in the extravesicular fraction of blood serum of pregnant women in the first trimester has prognostic significance in assessing the likelihood of developing early-onset PE (AUC = 0.97, Se = 1, Sp = 0.875, cutoff = 0.3877) and late-onset PE ( AUC = 1, Se = 1, Sp = 1, cutoff = 0.5).","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42710998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MV Porosyuk, DD Klementiev, NA Hodov, L. Gumenyuk, ES Esatova, EV Sereda, KS Chetveruhina-Malova, EV Sarchuk, SV Ivanov
Currently, the issue of the relationship between gut microbiota and juvenile idiopathic arthritis (JIA) is still relevant. The study was aimed to assess alterations in the gut microbiota taxonomic composition and estimate the relationship between these alterations and cortisol, melatonin, and TNFα at the genus level in patients with JIA. The comparative cross-sectional study involved 65 patients with JIA (index group) and 60 healthy children (control group). The gut microbiota taxonomic composition and plasma levels of cortisol, melatonin, and TNFα were assessed. The following alterations of the gut microbiota taxonomic composition were found in patients with JIA: the significantly decreased abundance of Anaerostipes (р = 0.042), Lachnospira (р = 0.034), Roseburia (р = 0.002), Coprococcus (р = 0.014), Dialister (р = 0.003) and the increase in the abundance of Ruminococcus (р = 0.012). There were significant correlations of cortisol levels with the abundance of Lachnospira (r = –0.44; p = 0.001), melatonin concentrations and the abundance of Coprococcus (r = –0.48; p = 0.023), the levels of TNFα and the abundance of Ruminococcus (r = 0.52; p = 0.001). The association of the Lachnospira, Roseburia, and Ruminococcus abundance with the higher DAS28 scores was discovered (r = –0.57; p = 0.002; r = –0.44; p = 0.002; r = 0.54; p = 0.032, respectively). The findings provide additional information about the features of gut microbiota alterations and their correlation with some hormone and inflammatory biomarkers associated with JIA, that could provide the basis for further research and possibly for new approaches to treatment of this disorder.
{"title":"Gut microbiota alterations in patients with juvenile idiopathic arthritis","authors":"MV Porosyuk, DD Klementiev, NA Hodov, L. Gumenyuk, ES Esatova, EV Sereda, KS Chetveruhina-Malova, EV Sarchuk, SV Ivanov","doi":"10.24075/brsmu.2022.060","DOIUrl":"https://doi.org/10.24075/brsmu.2022.060","url":null,"abstract":"Currently, the issue of the relationship between gut microbiota and juvenile idiopathic arthritis (JIA) is still relevant. The study was aimed to assess alterations in the gut microbiota taxonomic composition and estimate the relationship between these alterations and cortisol, melatonin, and TNFα at the genus level in patients with JIA. The comparative cross-sectional study involved 65 patients with JIA (index group) and 60 healthy children (control group). The gut microbiota taxonomic composition and plasma levels of cortisol, melatonin, and TNFα were assessed. The following alterations of the gut microbiota taxonomic composition were found in patients with JIA: the significantly decreased abundance of Anaerostipes (р = 0.042), Lachnospira (р = 0.034), Roseburia (р = 0.002), Coprococcus (р = 0.014), Dialister (р = 0.003) and the increase in the abundance of Ruminococcus (р = 0.012). There were significant correlations of cortisol levels with the abundance of Lachnospira (r = –0.44; p = 0.001), melatonin concentrations and the abundance of Coprococcus (r = –0.48; p = 0.023), the levels of TNFα and the abundance of Ruminococcus (r = 0.52; p = 0.001). The association of the Lachnospira, Roseburia, and Ruminococcus abundance with the higher DAS28 scores was discovered (r = –0.57; p = 0.002; r = –0.44; p = 0.002; r = 0.54; p = 0.032, respectively). The findings provide additional information about the features of gut microbiota alterations and their correlation with some hormone and inflammatory biomarkers associated with JIA, that could provide the basis for further research and possibly for new approaches to treatment of this disorder.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48197008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The HaCaT cell line represents the spontaneously immortalized non-carcinogenic human keratinocytes that are used as a model for studying the function of normal human keratinocytes. There are two TP53 alleles in the HaCaT cell genome, which comprise two gain-of-function (GOF) mutations acquired through spontaneous immortalization (mutTP53). Mutations result in the increased proliferation rate and violation of the stratification program. The study was aimed to assess the effects of the mutTP53 gene knockout on the HaCaT keratinocytes capability of proliferation and migration in the in vitro model of epidermal injury and regeneration (scratch test), and on the ability to form stratified epithelium in the organotypic epidermal model. To perform the scratch-test, cells were cultured until monolayer was formed, then the standardized injury was created. The organotypic model was obtained by growing keratinocytes in the polycarbonate membrane inserts with the pore size of 0.4 μm at the interface between the phases (air-liquid). It has been shown that the mutant TP53 gene knockout results in the increased migration capability of the HaCaT keratinocytes: in the HaCaT with the mutTP53 knockout, the defect closure occurred faster than in the appropriate group of the WT HaCaT (p < 0.05), on day three the defect size was 12% ± 3% and 66% ± 5% of the initial size. There is evidence that mutant TP53 in the HaCaT cells is a negative regulator of the laminin 5 expression (LAMC2 expression was 9.96 ± 1.92 times higher in the cells with the mutTP53 knockout, p < 0.05), however, this does not promote normalization of the program of epithelial differentiation and stratification followed by formation of the stratum corneum in the organotypic model.
{"title":"Knockout of mutant TP53 in the HaCaT cells enhances their migratory activity","authors":"P. Kozhin, D. Romashin, A. Rusanov, NG Luzgina","doi":"10.24075/brsmu.2022.070","DOIUrl":"https://doi.org/10.24075/brsmu.2022.070","url":null,"abstract":"The HaCaT cell line represents the spontaneously immortalized non-carcinogenic human keratinocytes that are used as a model for studying the function of normal human keratinocytes. There are two TP53 alleles in the HaCaT cell genome, which comprise two gain-of-function (GOF) mutations acquired through spontaneous immortalization (mutTP53). Mutations result in the increased proliferation rate and violation of the stratification program. The study was aimed to assess the effects of the mutTP53 gene knockout on the HaCaT keratinocytes capability of proliferation and migration in the in vitro model of epidermal injury and regeneration (scratch test), and on the ability to form stratified epithelium in the organotypic epidermal model. To perform the scratch-test, cells were cultured until monolayer was formed, then the standardized injury was created. The organotypic model was obtained by growing keratinocytes in the polycarbonate membrane inserts with the pore size of 0.4 μm at the interface between the phases (air-liquid). It has been shown that the mutant TP53 gene knockout results in the increased migration capability of the HaCaT keratinocytes: in the HaCaT with the mutTP53 knockout, the defect closure occurred faster than in the appropriate group of the WT HaCaT (p < 0.05), on day three the defect size was 12% ± 3% and 66% ± 5% of the initial size. There is evidence that mutant TP53 in the HaCaT cells is a negative regulator of the laminin 5 expression (LAMC2 expression was 9.96 ± 1.92 times higher in the cells with the mutTP53 knockout, p < 0.05), however, this does not promote normalization of the program of epithelial differentiation and stratification followed by formation of the stratum corneum in the organotypic model.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42874637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Salmasi, G. Poryadin, MI Panina, V. Larina, A. Ryzhikh, E. Stodelova, A. Kazimirskii
Post-COVID syndrome (long covid, post COVID-19 condition) is characterized by cognitive and mental disorders, chest and joint pain, impaired sense of smell and taste, as well as by gastrointestinal and cardiac disorders. The diagnosis of post-COVID syndrome is based mainly on the patients' complaints. To date, no optimal diagnostic method has been proposed. The study was aimed to compare the informative value of the indicators obtained during conventional assessment of patients with post-COVID syndrome and the blood levels of neutrophil (NETs) and monocyte (METs) extracellular traps. The study involved neutropils and monocytes collected from 21 patients with post-COVID syndrome aged 18–59. Fluorescence microscopy and the SYBR Green (Evrogen) fluorescent dye for double-stranded DNA were used for enumeration and imaging of extracellular traps. Clinical and laboratory indicators make it impossible to identify the changes specific for post-COVID syndrome. At the same time, post-COVID syndrome is characterized by inflammation in the vascular endothelium. The filamentous forms of NETs found in blood are a laboratory feature of such aseptic inflammation. The filamentous forms of NETs have been detected only in those patients who have a history of mild to severe СOVID-19, while the filamentous forms of METs have been found in patients having a history of severe infection. The findings show that the detection of the filamentous forms of NETs and METs in blood is the most informative diagnostic feature of post-COVID syndrome.
covid -19后综合征(长covid，后covid状态)的特征是认知和精神障碍，胸部和关节疼痛，嗅觉和味觉受损，以及胃肠道和心脏疾病。新冠肺炎后综合征的诊断主要基于患者的主诉。迄今为止，还没有提出最佳的诊断方法。本研究旨在比较新冠肺炎后综合征患者常规评估中获得的指标与血液中性粒细胞(NETs)和单核细胞(METs)细胞外陷阱水平的信息价值。该研究收集了21名年龄在18-59岁的后冠状病毒综合征患者的中性粒细胞和单核细胞。采用荧光显微镜和SYBR Green (Evrogen)双链DNA荧光染料对细胞外陷阱进行计数和成像。临床和实验室指标使得无法确定后冠状病毒综合征特有的变化。同时，新冠肺炎后综合征以血管内皮炎症为特征。在血液中发现的丝状net是无菌性炎症的实验室特征。丝状NETs仅在有轻度至重度СOVID-19病史的患者中检测到，而丝状METs在有严重感染史的患者中发现。研究结果表明，血液中丝状NETs和METs的检测是covid后综合征最有信息的诊断特征。
{"title":"Neutrophil and monocyte extracellular traps in the diagnosis of post-COVID syndrome","authors":"J. Salmasi, G. Poryadin, MI Panina, V. Larina, A. Ryzhikh, E. Stodelova, A. Kazimirskii","doi":"10.24075/brsmu.2022.057","DOIUrl":"https://doi.org/10.24075/brsmu.2022.057","url":null,"abstract":"Post-COVID syndrome (long covid, post COVID-19 condition) is characterized by cognitive and mental disorders, chest and joint pain, impaired sense of smell and taste, as well as by gastrointestinal and cardiac disorders. The diagnosis of post-COVID syndrome is based mainly on the patients' complaints. To date, no optimal diagnostic method has been proposed. The study was aimed to compare the informative value of the indicators obtained during conventional assessment of patients with post-COVID syndrome and the blood levels of neutrophil (NETs) and monocyte (METs) extracellular traps. The study involved neutropils and monocytes collected from 21 patients with post-COVID syndrome aged 18–59. Fluorescence microscopy and the SYBR Green (Evrogen) fluorescent dye for double-stranded DNA were used for enumeration and imaging of extracellular traps. Clinical and laboratory indicators make it impossible to identify the changes specific for post-COVID syndrome. At the same time, post-COVID syndrome is characterized by inflammation in the vascular endothelium. The filamentous forms of NETs found in blood are a laboratory feature of such aseptic inflammation. The filamentous forms of NETs have been detected only in those patients who have a history of mild to severe СOVID-19, while the filamentous forms of METs have been found in patients having a history of severe infection. The findings show that the detection of the filamentous forms of NETs and METs in blood is the most informative diagnostic feature of post-COVID syndrome.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42027319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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