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1.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Shinwari K., Wu Y., Rehman H., Xiao N., Bolkov M., Tuzankina I., Chereshnev V.
Заглавие : In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function
Место публикации : BMC Bioinformatics. - 2023. - Vol. 24. - Ст.251
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Аннотация: Hennekam Lymphangiectasia–Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.
https://link.springer.com/article/10.1186/s12859-023-05361-6
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2.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Saidakova E. V., Korolevskaya L. B., Shmagel N. G., Vlasova V. V., Shardina K. Yu., Chereshnev V. A., Shmagel K. V.
Заглавие : In HIV-infected immunological non-responders, hepatitis C virus eradication contributes to incomplete normalization of systemic inflammation, but does not lead to rapid CD4+ T-cell count recovery
Место публикации : Doklady Biochemistry and Biophysics. - 2023. - Vol. 512. - С. 274–278
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): hiv infections--hepatitis c--immunological non-response
Аннотация: In HIV-positive individuals taking antiretroviral therapy, coinfection with hepatitis C virus (HCV) increases systemic inflammation, which interferes with the CD4+ T-cells regeneration. This study evaluated the effect of HCV eradication on systemic inflammation and CD4+ T-cell regeneration in patients who gave poor response to antiretroviral therapy, the so-called “immunological non-responders” (INRs). HIV-infected patients who received a course of direct-acting antivirals for treating hepatitis C were examined. The control groups included HIV/HCV-coinfected INRs and relatively healthy volunteers. It was established for the first time that HCV eradication is not accompanied by a complete suppression of systemic inflammation, but improves the T-cell pool composition: in INRs, the blood CD4+/CD8+ T-lymphocyte ratio increases and approaches those of healthy individuals. Apparently, in INRs treated for hepatitis C, the immune system recovery takes time and may be incomplete.
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3.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Sobolevskaya P. A., Gvozdeckii A. N., Kudryavtsev I. V., Chereshnev V. A., Сhurilov L. P.
Заглавие : Role of proinflammatory cytokines in hashimoto's thyroiditis associated with psychiatric disorders
Место публикации : Medical Immunology. - 2023. - Vol. 25, № 5. - С. 1247-1252
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Аннотация: Mental disorders often accompany autoimmune diseases, for example, since 1949 it has been known about “myxedematous madness”, a psychosis caused by hypothyroidism. The most common cause of hypothyroidism is Hashimoto's autoimmune thyroiditis. It is also known about another neuropsychiatric disorder associated with autoimmune thyroiditis, Hashimoto's encephalopathy. It is a severe dysfunction of the central nervous system, the pathogenesis of which is not associated with hormonal disorders. Cytokines are regulators and participants of inflammation, including autoimmune. Certainly, when we are talking about high concentrations cytokines, we mean systemic inflammation. The minimal or mediocre fluctuations in cytokines within the ranges that are characteristic of healthy status or normergic acute phase response in disease cannot be interpreted from the point of view of binary endocrinological logic. In the CNS, cytokines are able to influence on the neuroendocrine control of systemically regulated functions. It is also important that glial cells (astroglia, microglia) are capable of producing a number of cytokines and can affect neurons and develop behavioral changes. In addition, the ability of a number of cytokines outside the CNS itself to act on vagal afferents and through them to convey information to the CNS, affecting its state and functions, has been proven. It is reasonable to assume that minimal fluctuations in cytokine levels may also affect the state and function of the CNS. The aim of the study was to investigate the levels of cytokines in patients with thyroiditis; in patients with thyroiditis associated with mental disorders; in a group of healthy individuals; and evaluate the effect of cytokine levels on clinical manifestations. In the group of patients with thyroiditis and mental disorders, the levels of CCL20/MIP3α, IL-13, IL-2, IL-27, IL-5 were significantly higher than in other groups. At the same time, no positive correlation was found between the clinical manifestations of mental disorders and the levels of cytokines. A positive correlation was found between the levels of some cytokines and free triiodothyronine, as well as the level of antithyroid antibodies. Mental disorders associated with autoimmune thyroiditis may be associated with changes in the cytokine profile and result from neuroinflammation.
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4.

Вид документа : Статья из журнала
Шифр издания : 61/I-34
Автор(ы) : Shinwari K., Chen Z., Liu Guojun, Chen L., Bolkov M. A., Tuzankina I. A., Chereshnev V. A.
Заглавие : Identification of the immune subtype among muscle-invasive bladder cancer patients by multiple datasets
Место публикации : Acta Medica Indonesiana. - 2022. - Vol. 54, № 1. - С. 62-71
ББК : 61
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): molecular subtype--immunotherapy--mibc
Аннотация: Background: Immunotherapies including PD-1/PD-L1 antibodies have been approved for the treatment of Muscle-invasive Bladder Cancer (MIBC) patients. However, immunotherapies could only be beneficial for about 20% MIBC patients. Thus, identification of the immune subtype is becoming increasingly important. This study aimed to explore the immune subtype by analyzing the gene expression profiles. Methods: A total of 6 datasets including (GSE13507, GSE31684, GSE32548, GSE32894, GSE69795, and TCGA-BLCA) were downloaded. The gene expression profiles from different datasets were combined since the batch effects were removed. We performed unsupervised clustering analysis to identify the immune subtype by the combined gene expression profiles. The tumor-infiltration levels of 22 immune cells, immune scores, and tumor purity were calculated, and the survival analysis was performed to investigate the prognosis difference between immune subtypes. The enriched pathways for each immune subtype were obtained. Results: We identified four novel immune subtypes (referred to S1, S2, S3, and S4) among MIBC patients. We found that S1 was enriched in immune scores had the best prognosis. In contrast, S3 was poor in immune scores and had the worst prognosis. Subtype S1, S2, S3, and S4 were enriched in immune-related pathways, extracellular matrix-related pathways, metabolism-related pathways, and cancer-related pathways, respectively. Conclusion: The current study suggests that the immune subtypes based on gene expression profiles could contribute to select the appropriate MIBC patient for immunotherapies.
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5.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Черешнев В. А., Оникиенко С. Б., Земляной А. В., Абкин С. В.
Заглавие : Применение защитных белков теплового шока-70 для борьбы с COVID-19
Место публикации : Журнал инфектологии. - 2022. - Т. 14, № 2, Приложение 1: Материалы VIII Конгресса Евро-Азиатского общества по инфекционным болезням, Санкт-Петербург, 17-19 мая 2022. - С. 134-135
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): covid 19--коронавирус--шок тепловой--белки защитные
Аннотация: We investigated the impact of bacterial regulators homoserine lactones (HSLs) and alkylhydroxybenzenes (AHBs) (which are present in human fluids at pico- and nanomolar concentrations) on neutrophile oxidative metabolism. The HSL and AHB effects were determined using a test based on induced luminol-dependent chemoluminescence of neutrophiles in human peripheral blood. In this test, neutrophiles were preincubated with chemical analogs of bacterial autoregulators with different lengths of the hydrocarbon radical, such as HSL · HCl, C6- and C12-HSL, and C1-, C6-, and C12-AHB. We revealed that they suppressed the chemoluminescence and, accordingly, the oxidative metabolism of neutrophiles. This effect was more significant with HSLs than with AHBs. Within each of the two groups, the effect increased with an increase in the length of the hydrocarbon chain of the homologues. High concentrations of long-chain autoregulators of both types produce a cytotoxic effect that is associated with apoptosis in the case of C12-HSL and with cell membrane damage in the case of C12-AHB. The effects of low HSL and AHB concentrations involve their protein-modifying properties and result in changes in the activities of neutrophile oxidative enzymes. To a lesser extent, these effects are due to the pro- and antioxidant activities of HSLs and AHBs, respectively. In light of the results obtained, the HSL and AHB effects are to be considered as a novel mechanism of regulating the activities of cell effectors of natural innate immunity. In symbiotic and parasitic systems, the mechanism involves the bimodal pattern of the effects of HSLs and AHBs that vary depending on their structure and concentrations
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6.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Shinwari K., Liu G., Bolkov M. A., Tuzankina I. A., Chereshnev V. A.
Заглавие : Checking gene expression profile associated with IRF7 and UNC93B deficient patient peripheral blood mononuclear cells infected with pH1N1 influenza virus
Место публикации : AIP Conference Proceedings. - 2022. - Vol. 2390, № 1. - Ст.030089
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): viruses--microarrays--genomics
Аннотация: An innate immune defect is a defect in the innate immune response that reduces the response to infection, this can occurs in genes important for activation regulation and proliferation of the innate immune cells or pathways important for the function of innate immunity. The purpose of this study was to identify novel biomarkers of interferon Receptor 7 through bioinformatics analysis and elucidate the possible molecular mechanism. The GSE 66486 datasets containing microarray data from IRF7 and UNC93B patients and healthy controls were downloaded from the GEO database and analyzed by the GEO2R web tool to obtain different expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI), and Biological Networks Gene Oncology tool (BiNGO) were then performed to elucidate the molecular mechanism of IRF7. A total of 490 DEGs were identified, of which 14 were hub genes, and involved in ribosome biogenesis, rRNA processing, gene expression, mRNA processing, nuclear lumen, intracellular non-membrane-bounded organelle, nucleoplasm, small-subunit processome, antigen processing and presentation pathway, and ribosome biogenesis in eukaryotes. Antigen processing and presentation pathway, and ribosome biogenesis in eukaryotes possibly form the basis of IRF7 or UNC93B disorders, while our study provides a list of genes and pathways that are disrupted in IRF7/UNC93B, which has the potential to be used in the clinic for diagnosis and targeted therapy of such disorders in future.
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7.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Shinwari K., Rehman H., Liu Guojun, Bolkov M. A., Tuzankina I. A., Chereshnev V. A.
Заглавие : Novel disease-associated missense single-nucleotide polymorphisms variants predication by algorithms tools and molecular dynamics simulation of human TCIRG1 gene causing congenital neutropenia and osteopetrosis
Место публикации : Frontiers in Molecular Biosciences. - 2022. - Vol. 9. - Ст.879875
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Аннотация: T Cell Immune Regulator 1, ATPase H + Transporting V0 Subunit A3 (TCIRG1 gene provides instructions for making one part, the a3 subunit, of a large protein complex known as a vacuolar H + -ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Single amino acid changes in highly conserved areas of the TCIRG1 protein have been linked to autosomal recessive osteopetrosis and severe congenital neutropenia. We used multiple computational approaches to classify disease-prone single nucleotide polymorphisms (SNPs) in TCIRG1. We used molecular dynamics analysis to identify the deleterious nsSNPs, build mutant protein structures, and assess the impact of mutation. Our results show that fifteen nsSNPs (rs199902030, rs200149541, rs372499913, rs267605221, rs374941368, rs375717418, rs80008675, rs149792489, rs116675104, rs121908250, rs121908251, rs121908251, rs149792489 and rs116675104) variants are likely to be highly deleterious mutations as by incorporating them into wild protein they destabilize the wild protein structure and function. They are also located in the V-ATPase I domain, which may destabilize the structure and impair TCIRG1 protein activation, as well as reduce its ATPase effectiveness. These mutants have not yet been identified in patients suffering from CN and osteopetrosis while (G405R, R444L, and D517N) reported in our study are already associated with osteopetrosis. Mutation V52L reported in our study was identified in a patient suspected for CN. Finally, these mutants can help to further understand the broad pool of illness susceptibilities associated with TCIRG1 catalytic kinase domain activation and aid in the development of an effective treatment for associated diseases.
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8.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Pashnina I. A., Krivolapova I. M., Fedotkina T. V., Ryabkova V. A., Chereshneva M. V., Churilov L. P., Chereshnev V. A.
Заглавие : Antinuclear autoantibodies in healthy individuals: autoimmunity is not a synonym of autoimmune disease : doi.org/10.3390/antib10010009
Место публикации : Antibodies. - 2021. - Vol. 10, № 1. - Ст.9
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Аннотация: Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.
\\\\Expert2\\NBO\\Электрон. библиотека (Отеч.периодика)\\Черешнев В. А\\Antibodies. - 2021. - Vol. 10, № 1. - Ст. 9.pdf
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9.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Pashnina I. A., Krivolapova I. M., Fedotkina T. V., Ryabkova V. A., Chereshneva M. V., Churilov L. P., Chereshnev V. A.
Заглавие : Antinuclear autoantibodies in healthy individuals: autoimmunity is not a synonym of autoimmune disease
Место публикации : Preprints. - 2020. - 28 Oct. - Ст.2020100591. - С. 27 p.
Предметные рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Аннотация: Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.
\\\\Expert2\\NBO\\Электрон. библиотека (Отеч.периодика)\\Черешнев В. А\\Preprints 2020 Ст. 2020100591.pdf
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10.

Вид документа : Статья из журнала
Шифр издания : 54
Автор(ы) : Sidorova L. P., Tseitler T. A., Emel’yanov V. V., Savateeva E. A., Maksimova N. E., Mochul’skaya N. N., Chereshnev V. A., Chupakhin O. N.
Заглавие : 2-Thiomorpholino-5-aryl-6 H-1,3,4-thiadiazine hydrobromides and their ability to inhibit nonenzymatic protein glycosylation
Место публикации : Pharmaceutical Chemistry Journal. - 2017. - Vol. 51, № 1. - С. 9-12
ББК : 54
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): glycosylation--esterification--glycosyl compounds--deglycosylation--?-halogenacetophenones--1,3,4-thiadiazine--4-morpholine thiosemicarbazides--cyclocondensation--nonenzymatic protein glycosylation
Аннотация: Cyclocondensation of α-halogenacetophenones with an original 4-morpholine thiosemicarbazide was used to synthesize a group of new Captions: of the 1,3,4-thiadiazine group, containing a thiomorpholine fragment at position 2 of the thiadiazine ring. Two members of this group of compounds were found to produce effective inhibition of nonenzymatic protein glycosylation in an in vitro model system. These test results allow compounds containing phenyl and fluorophenyl fragments IIIa and IIIb to be recommended for further study in in vivo experiments.
\\\\Expert2\\NBO\\Pharmaceutical Chemistry Journal\\2017 v.51 p.9-12.pdf
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