N. A. Lapkina, A. A. Baranov, O. P. Rechkina, N. E. Abaytova, S. S. Zolotavkina, A. S. Artyukhov, E. L. Nasonov
{"title":"IL-17A, IL-17F, and IL-23 in Patients with Rheumatoid Arthritis","authors":"N. A. Lapkina, A. A. Baranov, O. P. Rechkina, N. E. Abaytova, S. S. Zolotavkina, A. S. Artyukhov, E. L. Nasonov","doi":"10.1134/S1607672925700139","DOIUrl":"10.1134/S1607672925700139","url":null,"abstract":"<p>The aim of the study was to determine the clinical and diagnostic value of IL-17A, IL-17F, and IL-23 in RA patients in the advanced stage of the disease.</p><p><b>.</b> We examined 154 patients with a reliable diagnosis of RA according to ACR/EULAR criteria (2010), predominantly (73.4%) female, middle-aged (56.0 (50.0; 64.0) years), disease duration of 9.4 (3.0; 13.0) years, radiologic stages II (34.4%) and III (37.0%), and moderate to high activity (DAS28-ESR 5.40 (4.65; 6.00). Of these, 83.8% patients were seropositive for IgM rheumatoid factor (IgM RF), and 68.8% had antibodies to cyclic citrullinated peptide (ACCP). As many as 144 (93.5%) patients were taking DMARDs (methotrexate, leflunamide, and sulfasalazine), as well as nonsteroidal antiinflammatory drugs (NSAIDs) and glucocorticoids (GCs) up to 10 mg/day in terms of prednisolone.</p><p>The serum levels of IL-17A, IL-17F, and IL-23 were investigated using multiplex xMAR technology. The upper limit of the norm (M+3σ) in 20 sera of healthy donors was 1.78 pg/mL for IL-17A, 9.5 pg/mL for IL-17F, and 91.55 pg/mL for IL-23.</p><p>IL-17A (1.16 (0.50; 2.39) pg/mL) and IL-17F (5.02 (1.00; 138.80) pg/mL) concentrations in RA patients were not significantly different from controls (0.78 (0.00; 1.65) pg/mL and 4.02 (1.46; 7.31) pg/mL, <i>p</i> > 0.05). In contrast, IL-23 levels were significantly higher in patients than in donors (21.36 (2.50; 4626.22) pg/mL and 14.63 (0.00; 91.55) pg/mL, <i>p</i> < 0.05).</p><p>High values of IL-17F (71 patients, 46.1%) and IL-23 (66 patients, 42.9%) were significantly more frequently detected than IL-17A (46 patients, 29.9%: <i>p</i> = 0.003 and <i>p</i> = 0.02, respectively). Overproduction of IL-17A and IL-17F was simultaneously observed in 37 (24.0%) patients, and 32 (20.8%) patients had an increase in IL-17A, IL-17F, and IL-23. Correlations between IL-17A and IL-17F concentrations (<i>r</i> = 0.44, <i>p</i> < 0.05), IL-17A and IL-23 (<i>r</i> = 0.40, <i>p</i> < 0.05), IL-17F and IL-23 (<i>r</i> = 0.94, <i>p</i> < 0.05) were found.</p><p>No statistically significant differences were found between the concentration of IL-17A, IL-17F, and IL-23 and the frequency of their elevation in RA patients positive or negative for IgM RF, as well as for ACCP.</p><p>When IL-17A level was elevated, CDAI and SDAI indices and IgM RF concentration were significantly higher than in the comparison group (<i>p</i> < 0.05). In patients with IL-17F overproduction, predominance of ESR and CRP values was revealed in comparison with the normal values of this index (<i>p</i> < 0.05). At the same time, IL-17A concentration correlated with SDAI (<i>r</i> = 0.17, <i>p</i> < 0.05), IgM RF values (<i>r</i> = 0.19, <i>p</i> < 0.05), and ACCP (<i>r</i> = 0.19, <i>p</i> < 0.05). When IL-23 values were high, the HR was significantly lower (28, <i>p</i> < 0.05), and the groups did not differ in other indices of disease activity, IgM RF and ACCP. No differences i","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"369 - 374"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. L. Nasonov, V. I. Mazurov, A. M. Lila, T. V. Dubinina, I. Z. Gaidukova, S. A. Lapshina, A. A. Klimenko, D. V. Somov, S. A. Lukyanov, D. M. Chudakov, I. V. Zvyagin, O. V. Britanova, M. A. Korolev, D. I. Abdulganieva, D. G. Krechikova, A. A. Kastanayan, L. V. Eliseeva, R. R. Samigullina, T. V. Povarova, O. V. Antipova, S. A. Smakotina, V. N. Soboleva, O. B. Nesmeyanova, T. V. Plaksina, N. F. Soroka, I. B. Vinogradova, A. P. Rebrov, T. V. Kropotina, A. L. Maslyansky, A. V. Zinkina-Orikhan, Yu. N. Linkova, P. S. Pukhtinskaya, M. A. Morozova, G. A. Vinderskaya
{"title":"The Efficacy and Safety of BCD-180, an Anti-TRBV9+ T cell Monoclonal Antibody, in Patients with Active Radiographic Axial Spondyloarthritis: 36-week Results from the Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study ELEFTA","authors":"E. L. Nasonov, V. I. Mazurov, A. M. Lila, T. V. Dubinina, I. Z. Gaidukova, S. A. Lapshina, A. A. Klimenko, D. V. Somov, S. A. Lukyanov, D. M. Chudakov, I. V. Zvyagin, O. V. Britanova, M. A. Korolev, D. I. Abdulganieva, D. G. Krechikova, A. A. Kastanayan, L. V. Eliseeva, R. R. Samigullina, T. V. Povarova, O. V. Antipova, S. A. Smakotina, V. N. Soboleva, O. B. Nesmeyanova, T. V. Plaksina, N. F. Soroka, I. B. Vinogradova, A. P. Rebrov, T. V. Kropotina, A. L. Maslyansky, A. V. Zinkina-Orikhan, Yu. N. Linkova, P. S. Pukhtinskaya, M. A. Morozova, G. A. Vinderskaya","doi":"10.1134/S1607672925700140","DOIUrl":"10.1134/S1607672925700140","url":null,"abstract":"<p>The study aims to evaluate the clinical efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of seniprutug (BCD-180) in patients with active radiographic axial spondyloarthritis (r-axSpA, or ankylosing spondylitis).</p><p>Two hundred sixty patients with active r-axSpA and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs) were randomized into three groups to receive either seniprutug (BCD-180) 5 or 7 mg/kg, or placebo. BCD-180 was administered in the respective group dose using a 0–12–36 week regimen. The placebo group patients were switched to BCD-180 5 mg/kg at Week 24, with therapy continued at Week 36. The primary endpoint was the proportion of patients achieving 40% improvement in the Assessment in Spondyloarthritis International Society (ASAS40) score at Week 24.</p><p>The secondary endpoints included the proportion of patients achieving an ASAS20/40 response, improvement in 5 of 6 ASAS criteria (ASAS5/6), partial remission according to ASAS, ASDAS-CRP clinically important improvement in (Ankylosing Spondylitis Disease Activity Score with C-reactive protein level, ASDAS-CII) and ASDAS-CRP major improvement (ASDAS-MI). An analysis of changes over time in the disease activity status according to ASDAS-CRP, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, as well as changes over time in laboratory markers (CRP and erythrocyte sedimentation rate (ESR)) was also conducted. Safety was assessed based on the frequency and profile of adverse events (AE) and adverse reactions (AR).</p><p>The proportion of patients who achieved an ASAS40 response at Week 24 on seniprutug (BCD-180) at doses of 7 and 5 mg/kg was 51.4 and 40.8%, respectively, compared with 24% in the Placebo group (<i>p</i> = 0.0012 and <i>p</i> = 0.0417, respectively). Analysis of secondary endpoints showed that the efficacy of BCD-180 at both study doses was statistically significantly superior to placebo in patients with r-axSpA at Week 24 in the following respects: reduction in the proportion of subjects with very high disease activity (ASDAS-CRP > 3.5), achieving ASDAS-CII, ASAS20, ASAS5/6 response. A statistically significant decrease in the ASDAS-CRP, BASDAI, BASFI score, as well as CRP and ESR levels was demonstrated. Tolerability of seniprutug therapy was assessed as acceptable. The most common AEs were infusion-related reactions, most of which were mild to moderate according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events) and developed mainly during the first administration. The proportion of patients with detected binding antibodies was 5.1%. No neutralizing antibodies were detected.</p><p>Seniprutug (BCD-180) as a therapy for r-axSpA has demonstrated superiority over placebo in the clinical efficacy, a good safety profile and low immunogenicity.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"387 - 403"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. S. Avdeeva, A. P. Aleksankin, E. V. Chetina, Yu. N. Gorbunova, T. V. Popkova, G. A. Markova, T. A. Panafidina, E. L. Nasonov
{"title":"Immunophenotypes of Systemic Lupus Erythematosus—Features of Clinical and Laboratory Disorders","authors":"A. S. Avdeeva, A. P. Aleksankin, E. V. Chetina, Yu. N. Gorbunova, T. V. Popkova, G. A. Markova, T. A. Panafidina, E. L. Nasonov","doi":"10.1134/S1607672925700073","DOIUrl":"10.1134/S1607672925700073","url":null,"abstract":"<p>Objective: to evaluate subpopulations of B lymphocytes and features of interferon (IFN) status in patients with systemic lupus erythematosus (SLE), to clarify the relationship of immunological parameters with clinical manifestations of the disease.</p><p>A total of 139 patients (123 women (88%) and 16 men (12%)) with a definite diagnosis of SLE were included in the analysis. The disease duration was 3.0 [0.3; 12.0] years, SLEDAI-2K 7 [4; 11] points, SDI 0 [0; 1] points. Immunophenotyping of peripheral blood lymphocytes, including determination of B cells, the general population of memory B cells, non-switched and switched memory B cells, naive, transient B cells, and plasmablasts was carried out using multicolor flow cytometry. IFN status was assessed by the expression of IFN-stimulated genes (<i>MX1</i>, <i>RSAD2</i>, and <i>EPSTI1</i>) using real-time polymerase chain reaction.</p><p><b>.</b> Two immunological “patterns” were identified—the prevailing immunological mechanism of the pathogenesis of the disease (SLE) with predominant activation of type I IFN and with predominant activation of the B-cell component of the immune system. The immunological phenotype with activation of type I IFN was associated with high immunological activity, predominant skin damage, and leukopenia, whereas the phenotype with predominant activation of the B-cell component was associated with damage to the kidneys and nervous system.</p><p><b>.</b> The results of the work suggest a wide variety of immune mechanisms underlying the pathogenesis of SLE. It is possible to identify a number of leading molecular “patterns” of the pathogenesis of the disease, which must be taken into account to select an effective “targeted” drug.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"315 - 322"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. M. Ismailova, M. S. Severyukhina, E. R. Shaykhutdinova, N. A. Perepechenova, V. G. Starkov, I. A. Dyachenko, V. I. Tsetlin, Yu. N. Utkin
{"title":"Intravenous Administration of Heterodimeric Phospholipase A2 HDP-1 Disturbs Cardiovascular System Functions and Biochemical Composition of Blood in Anesthetized Rats","authors":"A. M. Ismailova, M. S. Severyukhina, E. R. Shaykhutdinova, N. A. Perepechenova, V. G. Starkov, I. A. Dyachenko, V. I. Tsetlin, Yu. N. Utkin","doi":"10.1134/S1607672925600137","DOIUrl":"10.1134/S1607672925600137","url":null,"abstract":"<p>Heterodimeric phospholipase A2 HDP-1 from the venom of Nikolsky viper consists of two noncovalently bound subunits—HDP-1P and HDP-1In, the first of which exhibits lipolytic activity, while the second does not. The subunits have similar molecular masses and amino acid sequences. Administration of HDP-1 and HDP-1P to anesthetized rats is accompanied by prolonged hypotensive effects, the intensity of which depends on the dose. After the administration of HDP-1P, the effect develops more slowly than in the case of HDP-1, containing both subunits, while individual HDP-1In does not affect hemodynamic parameters. It was found using electrocardiography that HDP-1 and HDP-1P affect the functioning of the rat heart, causing arrhythmia, which may indicate their ability to affect the innervation of the heart. The administration of HDP-1 and its subunits also leads to changes in blood biochemical parameters, indicating their damaging effect on cells and internal organs.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"273 - 278"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. E. Gubar, T. V. Korotaeva, T. V. Dubinina, L. D. Vorobyova, P. O. Tremaskina, E. M. Agafonova, Yu. L. Korsakova, E. Yu. Loginova, K. V. Sakharova, A. O. Sablina, A. V. Smirnov, Sh. F. Erdes, M. M. Urumova, S. I. Glukhova
{"title":"Comparative Characteristics of Axial Spondyloarthritis and Psoriatic Arthritis with Axial Involvement","authors":"E. E. Gubar, T. V. Korotaeva, T. V. Dubinina, L. D. Vorobyova, P. O. Tremaskina, E. M. Agafonova, Yu. L. Korsakova, E. Yu. Loginova, K. V. Sakharova, A. O. Sablina, A. V. Smirnov, Sh. F. Erdes, M. M. Urumova, S. I. Glukhova","doi":"10.1134/S1607672925700103","DOIUrl":"10.1134/S1607672925700103","url":null,"abstract":"<p>The aim of the study was to compare clinical characteristics of patients with axial spondyloarthritis (axSpA)/ankylosing spondylitis (AS) and with axial psoriatic arthritis (axPsA).</p><p><b>.</b> A total of 100 patients were examined: 45 with axSpA/AS (group 1) and 55 with axPsA (group 2). Patients of group 1 were included according to axSpA/AS criteria; patients of group 2, according to CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria, and having axial involvement (axPsA). Axial involvement was detected in case of radiologically significant sacroiliitis (SI, bilateral grade ≥2 or unilateral grade ≥3), or active MRI significant sacroiliitis, or ≥1 syndesmophyte(s) of the cervical and/or lumbar spine. Patients were evaluated for the presence of inflammatory back pain (IBP) by ASAS (Assessment of Spondyloarthritis International Society) criteria.</p><p>Patients of group 1 were younger (<i>p</i> < 0.001), more often were HLA-B27 positive (<i>p</i> < 0.001), and more often had IBP (<i>p</i> = 0.001). Patients of group 2 had older age (> 40 years) at back pain onset (<i>p</i> < 0.001) and more often had peripheral arthritis (<i>p</i> < 0.001), dactylitis (<i>p</i> = 0.004), and skin psoriasis (<i>p</i> < 0.001). Nail psoriasis was found only in group 2 patients (<i>p</i> < 0.001). Group 1 patients more often had heel enthesitis (<i>p</i> = 0.005). Group 2 patients had worse axial disease activity scores: BASDAI (Bath Ankylosing Spondylitis Disease Activity Index; <i>p</i> = 0.006) and ASDAS-СRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein level determination; <i>р</i> < 0.001); and worse patient-reported outcomes: BASFI (Bath Ankylosing Spondylitis Functional Index; <i>p</i> = 0.004), patients’ pain (<i>p</i> = 0.005) and patients’ global assessments (<i>p</i> = 0.036). Patients of group 2 had more syndesmophytes of the lumbar (<i>р</i> = 0.009) and cervical (<i>р</i> = 0.007) spine. Only in group 2 patients, chunky “non-marginal” syndesmophytes (in 32.1%), as well as spinal lesions without sacroiliitis (in 20.0%) were found. Patients of group 2 had more joint erosions (<i>р</i> = 0.001), osteolysis (<i>р</i> = 0.015), juxta-articular bone formation (<i>р</i> < 0.001) and joint ankyloses (<i>р</i> = 0.02). All patients of group 1 and only 80% of group 2 (<i>р</i> = 0.003) met ASAS criteria for axSpA. AxSpA/AS and axPsA seem to be two different diseases. In our cohort of patients, axPsA patients had worse disease status compared to axSp and AS.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"343 - 351"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. A. Blinova, A. V. Korechenkova, M. A. Yanishevskaya, A. V. Akleyev
{"title":"Effect of Repair Gene Polymorphism on the Risk of Malignant Neoplasm Development after Chronic Radiation Exposure","authors":"E. A. Blinova, A. V. Korechenkova, M. A. Yanishevskaya, A. V. Akleyev","doi":"10.1134/S1607672925700176","DOIUrl":"10.1134/S1607672925700176","url":null,"abstract":"<p>The efficiency of DNA integrity repair processes after radiation exposure may depend on hereditary variations of repair genes caused by single nucleotide polymorphisms. Disturbances or even failure of repair processes trigger a chain of reactions leading to genome instability and oncogenic transformation of the cell.</p><p>To investigate the association of single nucleotide polymorphism in genes of nucleotide excision repair (<i>ERCC2</i> rs13 181, <i>XPC</i> rs2 228 001), AP site repair (<i>APEX</i> rs1 130 409), homologous recombination (<i>XRCC3</i> rs861 539), single-strand DNA break repair (<i>XRCC1</i> rs25 487), and double-strand DNA break repair (<i>PARP</i> rs1 136 410, <i>XRCC4</i> rs2 075 685) with the risk of malignant neoplasm development of various localisations in chronically exposed persons.</p><p><b>.</b> The study was conducted in 861 persons who were exposed to chronic low dose rate radiation, 274 of which had malignant neoplasms (MN) of various localisations and 587 made up the comparison group (exposed persons without MN). The mean accumulated dose to red bone marrow (RBM) in the group of persons with MN was 561.65 ± 25.31 mGy, while in the comparison group it was 543.14 ± 36.06 mGy. Genotyping of polymorphic loci rs13181, rs2 228 001, rs1130409, rs861 539, rs25 487, rs1136410, and rs2075685 was performed by real-time PCR. The association of polymorphic loci with the risk of MN development was determined by the odds ratio (OR) and 95% confidence interval (95% CI). A multifactor dimensionality reduction method was used to assess intergenic interactions.</p><p>Single-stranded DNA break repair gene (<i>XRCC1</i>) rs25 487 polymorphism in accordance with the dominant model is associated with an increased risk of MN development in the combined group of the examined persons (OR = 1.79 (1.12–2.87), <i>p</i> = 0.01). The polymorphism of the gene involved in homologous recombination rs861539 (<i>XRCC3</i>) in accordance with the recessive model is associated with a reduced risk of MN development both in the combined group of exposed persons (OR = 0.25 (0.15–0.41; <i>p</i> < 0.00001), and separately in the group of the Slavs (OR = 0.28 (0.13–0.60); <i>p</i> < 0.0001) and in the group of the Turkic people (OR = 0.22 (0.11–0.44); <i>p</i> < 0.0001). The model of interfactorial interactions allowed us to establish a protective effect with respect to the risk of MN development in carriers of polymorphic loci rs861539 of the <i>XRCC3</i> gene and rs1130409 of the <i>APEX1</i> gene (<i>p</i> < 0.001).</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"410 - 417"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intravital Optical Bioimaging of Ovarian Cancer Using a Luminescent Cell Line","authors":"E. I. Shramova, G. M. Proshkina, S. M. Deyev","doi":"10.1134/S1607672925700188","DOIUrl":"10.1134/S1607672925700188","url":null,"abstract":"<p>Intravital bioimaging based on luminescence is an important method for the development and testing of antitumor drugs on model animals and is an essential part of preclinical studies. Bioimaging based on luminescent systems, compared with fluorescent bioimaging, provides a high signal-to-noise ratio, which justifies the development of cell lines that stably express luciferase genes for their subsequent use in model animals. In this work, we describe the creation of a stable cell line SKOV3.ip1-NanoLuc constitutively expressing the NanoLuc luciferase gene. The developed cell line was shown to be effective for intravital luminescence bioimaging of immunodeficient animals with deep-seated intraperitoneal tumors, which can be considered as a model of late-stage ovarian cancer.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"297 - 301"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Y. Agapkina, T. Y. Ponomareva, M. V. Vdovina, R. H. Ziganshin, A. A. Rozina, A. N. Anisenko, M. B. Gottikh
{"title":"New Cellular Partners of HIV-1 Integrase and their Role in Viral Replication","authors":"Y. Y. Agapkina, T. Y. Ponomareva, M. V. Vdovina, R. H. Ziganshin, A. A. Rozina, A. N. Anisenko, M. B. Gottikh","doi":"10.1134/S1607672925600149","DOIUrl":"10.1134/S1607672925600149","url":null,"abstract":"<p>Cellular proteins, partners of viral enzymes, are involved in the replication of human immunodeficiency virus type I (HIV-1) at various stages. Thus, the viral enzyme integrase, participating in several stages of the viral cycle, interacts with various cellular proteins. A number of them are already known, and for some the mechanism of action has been established, but the search for cellular partners of integrase continues. In this work, the identification of cellular partners of HIV-1 integrase has been carried out by the method of cross-linking followed by mass spectrometry (XL-MS). Twelve new potential integrase partners have been identified, and some of them have been examined for their effect on the early stages of HIV-1 replication.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"279 - 284"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. V. Gerasimova, T. V. Popkova, I. G. Kirillova, D. A. Gerasimova, E. L. Nasonov
{"title":"Dynamics of Modified Cardiovascular Risk Factors in Patients with Rheumatoid Arthritis on the Background of 5-Year Therapy with an Interleukin 6 Receptor Inhibitor","authors":"E. V. Gerasimova, T. V. Popkova, I. G. Kirillova, D. A. Gerasimova, E. L. Nasonov","doi":"10.1134/S1607672925700097","DOIUrl":"10.1134/S1607672925700097","url":null,"abstract":"<p>The effect of an inhibitor of interleukin (IL) 6 receptors on the state of the cardiovascular system in patients with rheumatoid arthritis (RA) remains poorly understood, especially with its long-term use.</p><p> of this work was to study the effect of therapy with the IL-6 receptor inhibitor tocilizumab (TCZ) on the dynamics of modifiable risk factors (RF), total cardiovascular risk (CVR), structural changes in the carotid arteries (CA), and the incidence of cardiovascular complications (CVC) in patients with rheumatoid arthritis during the 260-week follow-up period.</p><p>The study included 37 patients with active RA (32 women and 5 men) with ineffectiveness and/or intolerance to disease modifying anti-rheumatic drugs (DMARDs); median age was 56 [48; 68] years, disease duration was 92 [49; 158] months; DAS28 (Disease Activity Score 28)—6.2 [5.5; 6.7] points; all patients were seropositive for rheumatoid factor (RF), 86%—for antibodies to cyclic citrullinated peptide (ACCP). Patients received TCZ therapy 8 mg/kg intravenously every 4 weeks; after 192 [176; 210] weeks, 60% of patients switched to subcutaneous administration of the drug at a dose of 162 mg once a week. In 51% of patients with RA, TCZ monotherapy was performed, in 49%—combination therapy of TCZ with DMARDs. Statins were received by 17 (46%) patients, including 7 patients before and 10 after inclusion in the study. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE scale, atherosclerotic vascular lesions were assessed by the detection of atherosclerotic plaques (ASP) of CA. The observation period was 260.4 [251.5; 283.4] weeks.</p><p>After 260 weeks of TCZ therapy, RA remission was observed in 32 (86%) patients, low activity—in 5 (14%) patients. During the observation period, the frequency of modified RF and the total CVR did not change significantly, an increase in body mass index (BMI) by 11% was recorded, the number of patients with hypercholesterolemia and a reduced level of HDL cholesterol (C) decreased. In patients without statin therapy, there were no significant changes in the blood lipid spectrum. In the group of patients receiving statins, there was an increase in HDL-CH by 43%, a decrease in cholesterol levels by 15%, atherogenic index (AI) by 56% (<i>p</i> < 0.01 in all cases) and associations between the dynamics of ∆cholesterol and ∆CRP (<i>r</i> = 0.35; <i>p</i> = 0.04), ∆LDL-CH and ∆CRP (<i>r</i> = 0.41; <i>p</i> = 0.03). Significant structural changes in CA in RA patients by the end of 260 weeks of TCZ therapy were not identified. Initially, intima-media thickness (IMT) CA positively moderately correlated with age (<i>r</i> = 0.7; <i>p</i> < 0.01), BMI (<i>r</i> = 0.37; <i>p</i> < 0.01), systolic blood pressure (SBP) (<i>r</i> = 0.62; <i>p</i> < 0.01) and weakly with lipid spectrum parameters—cholesterol (<i>r</i> = 0.29; <i>p</i> < 0.01), LDL-CH (<i>r</i> = 0.36; <i>p</i","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"333 - 342"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. A. Dibrov, A. S. Avdeeva, M. E. Diatroptov, V. V. Rybakova, E. L. Nasonov
{"title":"Relation of Cytokine Profile and Antibody Values to Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis (Preliminary Data)","authors":"D. A. Dibrov, A. S. Avdeeva, M. E. Diatroptov, V. V. Rybakova, E. L. Nasonov","doi":"10.1134/S1607672925700115","DOIUrl":"10.1134/S1607672925700115","url":null,"abstract":"<p>The aim of the study was to investigate the correlation between cytokine levels and values of antibodies to cyclic citrullinated peptide (ACCP) and antibodies to carbamylated proteins (anti-CarP) in patients with rheumatoid arthritis (RA).</p><p><b>.</b> A total of 106 patients with a reliable diagnosis of rheumatoid arthritis were included in the study. Determination of anti-CarP and anti-CCP was performed by enzyme immunoassay. Patients were divided into subgroups depending on the values of ACCP and anti-CarP. The concentration of 27 cytokines in serum was determined using multiplex xMAR technology.</p><p><b>.</b> When comparing immunological subgroups, ACCP(+) patients had higher concentrations of IL-1β, IL-1Ra, IL-2, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, TGFb, TNF-α, and VEGF. IL-5, IL-9, eotaxin, MIP-1β, and RANTES values were higher in ACCP(–) patients. In the subgroup of ACCP(–) patients, an inverse correlation between IL-5 and total Sharpe score and between IL-9 and DAS28-CRP was found. In anti-CarP(–) patients (<i>n</i> = 73), higher values of IL-17 were recorded.</p><p><b>.</b> Our data support the concept of RA heterogeneity, characterized by the existence of different clinical and immunological subtypes, which may have implications for improving personalised therapy.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"522 1","pages":"352 - 357"},"PeriodicalIF":0.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}