A. Shestopalov, LA Ganenko, T. Grigoryeva, A. Laikov, I. Vasilyev, IM Kolesnikova, Y. Naboka, NI Volkova, S. Roumiantsev
Today, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are distinguished. Adipose and muscle tissues can determine the obese phenotype due to adipokine and myokine production. Gut microbial community is also involved in MHO. The study was aimed to reveal the features of adipokine and myokine levels and their association with the gut microbiome alpha diversity in patients with MHO and MUO. A total of 265 subjects were divided into two groups: healthy individuals and obese patients. The latter were divided into two subgroups: patients with MHO and patients with MUO. Body mass index, waist circumference, HOMA-IR, adipokine and myokine levels, gut microbiome taxonomic composition, alpha diversity indices were defined in all the surveyed individuals, lipid and carbohydrate metabolism was also assessed. Significant differences in the adipokine and myokine levels and their association with the gut microbiome diversity indicators were revealed in patients with different obese phenotypes. Patients with MHO and MUO showed significantly lower adiponectin levels (р < 0.05) and significantly higher leptin and asprosin levels (р < 0.05) than healthy individuals. Patients with MUO had lower adiponectin and leptin levels (p < 0.05) than patients with MHO. Significantly higher FGF21 levels were observed in patients with MUO. Large-scale correlation analysis revealed the relationship between the glucose levels and the gut microbiome diversity indices that was missing in patients with MUO. This indicated the loss of the microbiota diversity effects on the blood glucose control in individuals with MUO, as well as different regulatory roles in the gut microbiome‒liver‒muscle/adipose tissue axes of individuals with MHO and MUO played by gut microbiota. The findings show the relationship between the gut microbiome diversity and the obese phenotype.
{"title":"Adipokines and myokines as indicators of obese phenotypes and their association with the gut microbiome diversity indices","authors":"A. Shestopalov, LA Ganenko, T. Grigoryeva, A. Laikov, I. Vasilyev, IM Kolesnikova, Y. Naboka, NI Volkova, S. Roumiantsev","doi":"10.24075/brsmu.2023.004","DOIUrl":"https://doi.org/10.24075/brsmu.2023.004","url":null,"abstract":"Today, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are distinguished. Adipose and muscle tissues can determine the obese phenotype due to adipokine and myokine production. Gut microbial community is also involved in MHO. The study was aimed to reveal the features of adipokine and myokine levels and their association with the gut microbiome alpha diversity in patients with MHO and MUO. A total of 265 subjects were divided into two groups: healthy individuals and obese patients. The latter were divided into two subgroups: patients with MHO and patients with MUO. Body mass index, waist circumference, HOMA-IR, adipokine and myokine levels, gut microbiome taxonomic composition, alpha diversity indices were defined in all the surveyed individuals, lipid and carbohydrate metabolism was also assessed. Significant differences in the adipokine and myokine levels and their association with the gut microbiome diversity indicators were revealed in patients with different obese phenotypes. Patients with MHO and MUO showed significantly lower adiponectin levels (р < 0.05) and significantly higher leptin and asprosin levels (р < 0.05) than healthy individuals. Patients with MUO had lower adiponectin and leptin levels (p < 0.05) than patients with MHO. Significantly higher FGF21 levels were observed in patients with MUO. Large-scale correlation analysis revealed the relationship between the glucose levels and the gut microbiome diversity indices that was missing in patients with MUO. This indicated the loss of the microbiota diversity effects on the blood glucose control in individuals with MUO, as well as different regulatory roles in the gut microbiome‒liver‒muscle/adipose tissue axes of individuals with MHO and MUO played by gut microbiota. The findings show the relationship between the gut microbiome diversity and the obese phenotype.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49294329","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}
T. Ozharovskaia, O. Popova, O. Zubkova, IV Vavilova, A. Pochtovyy, D. Shcheblyakov, VA Gushchin, D. Logunov, A. Gintsburg
Technological versatility and the humoral and cellular immune response induction capacity have conditioned wide spread of adenoviral vectors as vaccine and gene therapy drugs. However, vaccination with Sputnik V made a significant portion of the population immune to the types 5 and 26 (Ad5 and Ad26) recombinant human adenovirus vectors, which are some of the most frequently used bases for candidate vaccines. Today, vaccine designers tend to select alternative adenovirus serotypes as platforms to develop vaccines against new pathogens on. A good example is simian adenovirus type 25 (SAd25), which belongs to subgroup E. It is genetically distant from Ad5 and exhibits extremely low seroprevalence in human beings, which makes it an appealing alternative vaccine vector. The purpose of this work was to design and study a new vaccine platform based on simian adenovirus type 25. We relied on the advanced methods of molecular biology and virology to construct and make recombinant adenoviruses; the phylogenetic analysis in the context of this study was enabled with bioinformatic methods. The resulting recombinant adenoviral vector can effectively replicate itself in the HEK293 cell line (human embryonic kidney cells). This work substantiates the expediency of further investigation into the SAd25 vector as a platform for development of the prevention vaccines against various infectious diseases.
{"title":"Development and characterization of a vector system based on the simian adenovirus type 25","authors":"T. Ozharovskaia, O. Popova, O. Zubkova, IV Vavilova, A. Pochtovyy, D. Shcheblyakov, VA Gushchin, D. Logunov, A. Gintsburg","doi":"10.24075/brsmu.2023.006","DOIUrl":"https://doi.org/10.24075/brsmu.2023.006","url":null,"abstract":"Technological versatility and the humoral and cellular immune response induction capacity have conditioned wide spread of adenoviral vectors as vaccine and gene therapy drugs. However, vaccination with Sputnik V made a significant portion of the population immune to the types 5 and 26 (Ad5 and Ad26) recombinant human adenovirus vectors, which are some of the most frequently used bases for candidate vaccines. Today, vaccine designers tend to select alternative adenovirus serotypes as platforms to develop vaccines against new pathogens on. A good example is simian adenovirus type 25 (SAd25), which belongs to subgroup E. It is genetically distant from Ad5 and exhibits extremely low seroprevalence in human beings, which makes it an appealing alternative vaccine vector. The purpose of this work was to design and study a new vaccine platform based on simian adenovirus type 25. We relied on the advanced methods of molecular biology and virology to construct and make recombinant adenoviruses; the phylogenetic analysis in the context of this study was enabled with bioinformatic methods. The resulting recombinant adenoviral vector can effectively replicate itself in the HEK293 cell line (human embryonic kidney cells). This work substantiates the expediency of further investigation into the SAd25 vector as a platform for development of the prevention vaccines against various infectious diseases.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44694732","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}
Several COVID-19 vaccines have been developed in the last three years using various tecnhiques. Multiple virus-neutralizing antibodies against SARS-CoV-2 have been also obtained to combat the pandemic. However, the use of these medications for prevention and potential treatment faces significant challenges due to the emergence of new mutant virus variants, both more contagious and escaping neutralization by the immune system, that is why it is necessary to continuously renew the vaccines and develop new therapeutic antibodies. The study was aimed to use the technology of generating single-domain antibodies (nanobodies) to target the surface spike (S) protein RBD conserved epitope of the broad spectrum of SARS-CoV-2 variants. Recombinant proteins that corresponded to RBDs of three important SARS-СoV-2 strains and the full-length S protein (Wuhan) were used as antigens for immunization of a camel in order to induce production of appropriate antibodies and/or as immobilized proteins for further cross selection of the nanobody clones with pre-set specificity by the phage display. A nanobody capable of effectively recognizing the conservative region in the S protein RBDs of the broad spectrum of pandemic SARS-CoV-2 variants, including Omicron, was selected from the generated immune library. Along with conventional use in immunoassays and diagnosis, the generated nanobody can be potentially used as a module for target-specific binding used to trap coronavirus in human upper airways during the development of novel combination antiviral drugs.
{"title":"Single-domain antibody for binding the conserved epitope in the SARS-CoV-2 spike protein receptor-binding domain","authors":"P. Vorobyev, SV Tillib","doi":"10.24075/brsmu.2023.005","DOIUrl":"https://doi.org/10.24075/brsmu.2023.005","url":null,"abstract":"Several COVID-19 vaccines have been developed in the last three years using various tecnhiques. Multiple virus-neutralizing antibodies against SARS-CoV-2 have been also obtained to combat the pandemic. However, the use of these medications for prevention and potential treatment faces significant challenges due to the emergence of new mutant virus variants, both more contagious and escaping neutralization by the immune system, that is why it is necessary to continuously renew the vaccines and develop new therapeutic antibodies. The study was aimed to use the technology of generating single-domain antibodies (nanobodies) to target the surface spike (S) protein RBD conserved epitope of the broad spectrum of SARS-CoV-2 variants. Recombinant proteins that corresponded to RBDs of three important SARS-СoV-2 strains and the full-length S protein (Wuhan) were used as antigens for immunization of a camel in order to induce production of appropriate antibodies and/or as immobilized proteins for further cross selection of the nanobody clones with pre-set specificity by the phage display. A nanobody capable of effectively recognizing the conservative region in the S protein RBDs of the broad spectrum of pandemic SARS-CoV-2 variants, including Omicron, was selected from the generated immune library. Along with conventional use in immunoassays and diagnosis, the generated nanobody can be potentially used as a module for target-specific binding used to trap coronavirus in human upper airways during the development of novel combination antiviral drugs.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47305750","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}
Due to the changes in the modern world, it is necessary to develop the domestic pharmaceutical industry, which is a task especially important in the context of implementation of the import substitution policy. The article classifies the main measures the state industrial policy has for the pharmaceutical industry; these measures cover informational and consulting aspects, research and technical parts, innovations and economic matters. Practical actions and their possible consequences are considered for each group of the industrial policy measures: encouragement of domestic consumption, regulation of imports, stimulation and support of exports, stimulation of technological development, public-private partnerships, support of the development of intersectoral territorial production complexes (clusters), direct state support of investment activities, tax incentives for investors.
{"title":"Main state industrial policy measures for the pharmaceutical industry of the Russian Federation","authors":"TY Gaydin, EV Geller, S. Rozhnova, T. Gaydina","doi":"10.24075/brsmu.2023.007","DOIUrl":"https://doi.org/10.24075/brsmu.2023.007","url":null,"abstract":"Due to the changes in the modern world, it is necessary to develop the domestic pharmaceutical industry, which is a task especially important in the context of implementation of the import substitution policy. The article classifies the main measures the state industrial policy has for the pharmaceutical industry; these measures cover informational and consulting aspects, research and technical parts, innovations and economic matters. Practical actions and their possible consequences are considered for each group of the industrial policy measures: encouragement of domestic consumption, regulation of imports, stimulation and support of exports, stimulation of technological development, public-private partnerships, support of the development of intersectoral territorial production complexes (clusters), direct state support of investment activities, tax incentives for investors.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48462059","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}
Fuchs' endothelial corneal dystrophy is a socially significant hereditary disease. More than a half of cases in the European population are caused by the increased number of trinucleotude repeats in the TCF4 gene. The study was aimed to develop and test the approach of dividing patients into groups based on the chip-based genotyping and genome-wide association study (GWAS) results. The analysis was conducted using FECD Genetics Multi-center Study and AREDs project datasets containing the data of 1721 clinical cases and 2408 control patients. When analyzing the GWAS results, the patients and the control group were divided into two groups by means of hierarchical clustering suggesting that patients with the increased number of repeats in the TCF4 gene are carriers of specific combinations of genomic variants (haplotypes). It was shown that individual variants cannot be used for the molecular genetic stratification of patients with the increased number of repeats in TCF4 due to inconsistent results obtained for the variants. Furthermore, the haplotype-based approach outperformed the SNPs in terms of odds ratio. The paper proposes a method that enables further search for the biologically relevant combinations of genomic variants.
{"title":"The approach to patient clustering based on the microchip data confined to distinct loci using the combinations of variants","authors":"LN Iulmetova, NA Kulemin, EI Sharova","doi":"10.24075/brsmu.2023.001","DOIUrl":"https://doi.org/10.24075/brsmu.2023.001","url":null,"abstract":"Fuchs' endothelial corneal dystrophy is a socially significant hereditary disease. More than a half of cases in the European population are caused by the increased number of trinucleotude repeats in the TCF4 gene. The study was aimed to develop and test the approach of dividing patients into groups based on the chip-based genotyping and genome-wide association study (GWAS) results. The analysis was conducted using FECD Genetics Multi-center Study and AREDs project datasets containing the data of 1721 clinical cases and 2408 control patients. When analyzing the GWAS results, the patients and the control group were divided into two groups by means of hierarchical clustering suggesting that patients with the increased number of repeats in the TCF4 gene are carriers of specific combinations of genomic variants (haplotypes). It was shown that individual variants cannot be used for the molecular genetic stratification of patients with the increased number of repeats in TCF4 due to inconsistent results obtained for the variants. Furthermore, the haplotype-based approach outperformed the SNPs in terms of odds ratio. The paper proposes a method that enables further search for the biologically relevant combinations of genomic variants.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47639224","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}
Dmitry S. Sitnikov, I. Ilina, M. Filatov, YY Silaeva
The zona pellucida (ZP) is a dynamically changing object that plays an important role during the preimplantation stage of embryogenesis. The ZP thickness may affect the implantation success and pregnancy rate, it is considered as a prognostic factor in a number of studies. The study was aimed to assess the dynamic changes in the mouse embryonic ZP thickness after laser assisted hatching (LAH) that involved breaching the ZP integrity at the blastocyst stage. Femtosecond laser pulses were used to perform the zona microsurgery. The zona thickness was measured both at the stage of blastocyst microsurgery (~Е3.5, i.e. 3.5 days of embryogenesis) and at the hatching stage (~Е5). Significant differences in the ZP thickness were revealed in the control group of embryos: from 6.21 µm (Е3.5) to 5.4 µm (Е5). The changes in thickness from 6.6 µm (Е3.5) to 6.2 µm (Е5) observed in the group subjected to LAH were non-significant. Tracing the ZP thickness of a particular embryo from the blastocyst stage to the hatching stage made it possible to estimate the thinning coefficients in the experimental and control groups. The findings that indicate lower tensile strength of the zona in case of LAH can provide the basis for further research on the ZP properties in case of using the embryo cryopreservation protocols.
{"title":"Assessment of the zona pellucida microdissection on its thickness in mammalian embryos","authors":"Dmitry S. Sitnikov, I. Ilina, M. Filatov, YY Silaeva","doi":"10.24075/brsmu.2023.002","DOIUrl":"https://doi.org/10.24075/brsmu.2023.002","url":null,"abstract":"The zona pellucida (ZP) is a dynamically changing object that plays an important role during the preimplantation stage of embryogenesis. The ZP thickness may affect the implantation success and pregnancy rate, it is considered as a prognostic factor in a number of studies. The study was aimed to assess the dynamic changes in the mouse embryonic ZP thickness after laser assisted hatching (LAH) that involved breaching the ZP integrity at the blastocyst stage. Femtosecond laser pulses were used to perform the zona microsurgery. The zona thickness was measured both at the stage of blastocyst microsurgery (~Е3.5, i.e. 3.5 days of embryogenesis) and at the hatching stage (~Е5). Significant differences in the ZP thickness were revealed in the control group of embryos: from 6.21 µm (Е3.5) to 5.4 µm (Е5). The changes in thickness from 6.6 µm (Е3.5) to 6.2 µm (Е5) observed in the group subjected to LAH were non-significant. Tracing the ZP thickness of a particular embryo from the blastocyst stage to the hatching stage made it possible to estimate the thinning coefficients in the experimental and control groups. The findings that indicate lower tensile strength of the zona in case of LAH can provide the basis for further research on the ZP properties in case of using the embryo cryopreservation protocols.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41658980","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}
O. Rogovaya, EV Alpeeva, E. Ruchko, A. Eremeev, EA Vorotelyak
Tissue-engineered constructs (TECs), the dermal equivalent (DE) and the skin equivalent (SE), are allogenic equivalents of the skin and derm used to treat critical skin loss. Selection of storage conditions that contribute to longer shelf life, thereby expanding the possibilities of logistics and use, is one of the major issues related to the TECs development. The study was aimed to determine the shelf life of the DE and SE TECs stored in normal saline at room temperature by assessing morphology and viability of the cells on their surface, along with the levels of endothelial growth factor (VEGF) secreted by these cells. Using the MTT assay and staining with vital dye, we discovered the following: when TECs of both types were stored in normal saline, the cells viability and metabolic activity decreased by more than 50% by days 3–4 of storage. Furthermore, these decreased faster in DEs than in SEs. Morphology of the cells isolated from DEs and SEs after the 3-day storage remained unchanged. Mesenchymal stem cells on the surface of TECs kept producing VEGF after TECs culture medium was changed for saline solution (confirmed by immunofluorescence assay), which could indicate that the cells retained essential secretory activity.
{"title":"Survival of human cells in tissue-engineered constructs stored at room temperature","authors":"O. Rogovaya, EV Alpeeva, E. Ruchko, A. Eremeev, EA Vorotelyak","doi":"10.24075/brsmu.2023.003","DOIUrl":"https://doi.org/10.24075/brsmu.2023.003","url":null,"abstract":"Tissue-engineered constructs (TECs), the dermal equivalent (DE) and the skin equivalent (SE), are allogenic equivalents of the skin and derm used to treat critical skin loss. Selection of storage conditions that contribute to longer shelf life, thereby expanding the possibilities of logistics and use, is one of the major issues related to the TECs development. The study was aimed to determine the shelf life of the DE and SE TECs stored in normal saline at room temperature by assessing morphology and viability of the cells on their surface, along with the levels of endothelial growth factor (VEGF) secreted by these cells. Using the MTT assay and staining with vital dye, we discovered the following: when TECs of both types were stored in normal saline, the cells viability and metabolic activity decreased by more than 50% by days 3–4 of storage. Furthermore, these decreased faster in DEs than in SEs. Morphology of the cells isolated from DEs and SEs after the 3-day storage remained unchanged. Mesenchymal stem cells on the surface of TECs kept producing VEGF after TECs culture medium was changed for saline solution (confirmed by immunofluorescence assay), which could indicate that the cells retained essential secretory activity.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48651446","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}
M. Postnikov, AV Butvilovsky, Aam Alsharifi, AV Madatyan, I. Kopetskiy, D. Eremin
Anatomical features of the teeth should be accounted for dental treatment plans. The need for constant monitoring of changes in the dentition system determines the relevance of this research. The study aimed to establish the size of anterior teeth with the help of odontometry. We made bi-layer single stage impressions and cast diagnostic models of the anterior teeth of 50 male and 50 female participants aged 18–24 years. The absolute sizes of crowns of incisors and canines were established. To assess the reduction of lateral incisors, we calculated the interincisor index (Ii) of teeth 22 and 21; sexual dimorphism was determined using the Garn–Lewis formula. It was discovered that there are no differences in the mesiodistal widths of crowns of contralateral teeth on the right and left sides (p > 0.05). The mesiodistal width of crowns of anterior teeth decreases (significant changes) in the following order: maxillary central incisors → maxillary canines → mandibular canines and maxillary lateral incisors → mandibular lateral incisors → mandibular central incisors. The degree of reduction of lateral incisors is low (Ii = 74.9) and more prominent in males than in females. In the examined patients, the greatest mean length of crowns of anterior teeth is that of upper central incisors and lower canines, while upper canines are shorter in length and upper lateral incisors, lower central and lateral incisors have the shortest mean crown length. Males have longer (mean length) crowns of lower canines, upper incisors and canines than females, the difference being significant (p < 0.001). The parameters of the crowns determined in this study showed that they have sufficient height and mesiodistal width, which, together with the low degree of reduction of the lateral incisors, justifies the possibility of direct fabrication of orthodontic fixed retainers. The data can also be used at the stage of dental treatment planning.
{"title":"Justification of use of fixed retainers based on the analysis of size of the incisor and canine crowns","authors":"M. Postnikov, AV Butvilovsky, Aam Alsharifi, AV Madatyan, I. Kopetskiy, D. Eremin","doi":"10.24075/brsmu.2022.069","DOIUrl":"https://doi.org/10.24075/brsmu.2022.069","url":null,"abstract":"Anatomical features of the teeth should be accounted for dental treatment plans. The need for constant monitoring of changes in the dentition system determines the relevance of this research. The study aimed to establish the size of anterior teeth with the help of odontometry. We made bi-layer single stage impressions and cast diagnostic models of the anterior teeth of 50 male and 50 female participants aged 18–24 years. The absolute sizes of crowns of incisors and canines were established. To assess the reduction of lateral incisors, we calculated the interincisor index (Ii) of teeth 22 and 21; sexual dimorphism was determined using the Garn–Lewis formula. It was discovered that there are no differences in the mesiodistal widths of crowns of contralateral teeth on the right and left sides (p > 0.05). The mesiodistal width of crowns of anterior teeth decreases (significant changes) in the following order: maxillary central incisors → maxillary canines → mandibular canines and maxillary lateral incisors → mandibular lateral incisors → mandibular central incisors. The degree of reduction of lateral incisors is low (Ii = 74.9) and more prominent in males than in females. In the examined patients, the greatest mean length of crowns of anterior teeth is that of upper central incisors and lower canines, while upper canines are shorter in length and upper lateral incisors, lower central and lateral incisors have the shortest mean crown length. Males have longer (mean length) crowns of lower canines, upper incisors and canines than females, the difference being significant (p < 0.001). The parameters of the crowns determined in this study showed that they have sufficient height and mesiodistal width, which, together with the low degree of reduction of the lateral incisors, justifies the possibility of direct fabrication of orthodontic fixed retainers. The data can also be used at the stage of dental treatment planning.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44273564","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}
VI Shmygarev, YuA Prokopenko, S. Terekhov, MYu Zakharova, M. Dubinnyi, I. Smirnov, IV Yampolsky, A. Tsarkova
Coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, is highly contagious and has a severe morbidity. Providing care to patients with COVID-19 requires the development of new types of antiviral drugs. The aim of this work is to develop a prodrug for the treatment of coronavirus disease using the antibiotic Amicoumacin A (Ami), the mechanism of action of which is based on translation inhibition. Enzymatic hydrolysis of an inactivated prodrug by the SARS-CoV-2 main protease can lead to the release of the active Ami molecule and, as a consequence, the suppression of protein biosynthesis in infected cells. To test the proposed hypothesis, a five-stage synthesis of an inactivated analogue of Amicoumacin A was carried out. Its in vitro testing with the SARS-CoV-2 recombinant protease MPro showed a low percentage of hydrolysis. Further optimization of the peptide fragment of the inactivated analog recognized by the SARS-CoV-2 MPro protease may lead to an increase in proteolysis and the release of Amicoumacin A.
由SARS-CoV-2病毒引起的冠状病毒病COVID-19具有高度传染性，发病率很高。为COVID-19患者提供护理需要开发新型抗病毒药物。本研究的目的是利用抗生素Amicoumacin a (Ami)开发一种治疗冠状病毒疾病的前药，其作用机制基于翻译抑制。SARS-CoV-2主要蛋白酶对失活前药的酶解可导致活性Ami分子的释放，从而抑制受感染细胞中的蛋白质生物合成。为了验证所提出的假设，进行了Amicoumacin a的失活类似物的五阶段合成。其与SARS-CoV-2重组蛋白酶MPro的体外测试显示水解率低。进一步优化SARS-CoV-2 MPro蛋白酶识别的失活类似物的肽片段可能导致蛋白水解和Amicoumacin A的释放增加。
{"title":"Amicoumacin-based prodrug development approach","authors":"VI Shmygarev, YuA Prokopenko, S. Terekhov, MYu Zakharova, M. Dubinnyi, I. Smirnov, IV Yampolsky, A. Tsarkova","doi":"10.24075/brsmu.2022.073","DOIUrl":"https://doi.org/10.24075/brsmu.2022.073","url":null,"abstract":"Coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, is highly contagious and has a severe morbidity. Providing care to patients with COVID-19 requires the development of new types of antiviral drugs. The aim of this work is to develop a prodrug for the treatment of coronavirus disease using the antibiotic Amicoumacin A (Ami), the mechanism of action of which is based on translation inhibition. Enzymatic hydrolysis of an inactivated prodrug by the SARS-CoV-2 main protease can lead to the release of the active Ami molecule and, as a consequence, the suppression of protein biosynthesis in infected cells. To test the proposed hypothesis, a five-stage synthesis of an inactivated analogue of Amicoumacin A was carried out. Its in vitro testing with the SARS-CoV-2 recombinant protease MPro showed a low percentage of hydrolysis. Further optimization of the peptide fragment of the inactivated analog recognized by the SARS-CoV-2 MPro protease may lead to an increase in proteolysis and the release of Amicoumacin A.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47057355","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. Novoselova, M. Yushina, M. Patysheva, EA Prostashkina, O. Bragina, E. Garbukov, J. Kzhyshkowska
Monocytes are large circulating white blood cells that are the main precursors of tissue macrophages as well as tumor-associated macrophages in the adult body. Different types of monocytes have multidirectional effects on the growth and metastatic spread of cancer cells, both activating and inhibiting these processes. Tumor progression is associated with the triggering of a whole cascade of inflammatory and immune reactions. These pathological processes are associated with changes in the amino acid content of monocytes, which can lead to disruption of their function, in particular their migration, division and maturation. The aim of the work was to profile the amino acids of monocytes, followed by a study of the amino acid composition of monocytes from patients with breast cancer using liquid chromatography with mass spectrometric detection. Significant differences in metabolite levels in monocytes of breast cancer patients and monocytes of healthy donors were found for glycine (p-value = 0.0127), asparagine (p-value = 0.0197), proline (p-value = 0.0159), methionine (p-value = 0.0357), tryptophan (p-value = 0.0028), tyrosine (p-value = 0.0127). In the study, we identified biological networks that could potentially be involved in altering the phenotype of monocytes affected by breast cancer (BC), using bioinformatic analysis of metabolic pathways involving the discovered amino acids. Mathematical models based on amino acid combinations with 100% sensitivity and specificity have been developed. Features of immune system cell metabolism in BC have been identified and potential diagnostic biomarkers have been proposed.
{"title":"Peculiarities of amino acid profile in monocytes in breast cancer","authors":"A. Novoselova, M. Yushina, M. Patysheva, EA Prostashkina, O. Bragina, E. Garbukov, J. Kzhyshkowska","doi":"10.24075/brsmu.2022.064","DOIUrl":"https://doi.org/10.24075/brsmu.2022.064","url":null,"abstract":"Monocytes are large circulating white blood cells that are the main precursors of tissue macrophages as well as tumor-associated macrophages in the adult body. Different types of monocytes have multidirectional effects on the growth and metastatic spread of cancer cells, both activating and inhibiting these processes. Tumor progression is associated with the triggering of a whole cascade of inflammatory and immune reactions. These pathological processes are associated with changes in the amino acid content of monocytes, which can lead to disruption of their function, in particular their migration, division and maturation. The aim of the work was to profile the amino acids of monocytes, followed by a study of the amino acid composition of monocytes from patients with breast cancer using liquid chromatography with mass spectrometric detection. Significant differences in metabolite levels in monocytes of breast cancer patients and monocytes of healthy donors were found for glycine (p-value = 0.0127), asparagine (p-value = 0.0197), proline (p-value = 0.0159), methionine (p-value = 0.0357), tryptophan (p-value = 0.0028), tyrosine (p-value = 0.0127). In the study, we identified biological networks that could potentially be involved in altering the phenotype of monocytes affected by breast cancer (BC), using bioinformatic analysis of metabolic pathways involving the discovered amino acids. Mathematical models based on amino acid combinations with 100% sensitivity and specificity have been developed. Features of immune system cell metabolism in BC have been identified and potential diagnostic biomarkers have been proposed.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45801372","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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