Doklady Biochemistry and Biophysics最新文献

{"title":"Antitumor Effect of Helium Ions with Energy of 320 MeV/Ion during Irradiation of Ehrlich Ascites Carcinoma Cells Ex Vivo.","authors":"V E Balakin, N S Strelnikova, O M Rozanova, E N Smirnova, T A Belyakova, A E Shemyakov","doi":"10.1134/S1607672925600356","DOIUrl":"https://doi.org/10.1134/S1607672925600356","url":null,"abstract":"<p><p>The regularities of tumor induction and growth were studied in mice after a single ex vivo irradiation with a helium ion beam of Ehrlich adenocarcinoma ascites cells (EAC) at doses of 10 and 20 Gy in two positions of the Bragg curve (before the peak and at the peak) in comparison with X-ray radiation at the same doses. It was shown that the frequency of induction and delay in tumor appearance depend on the dose of helium ion irradiation. The following parameters were determined: the time of a fivefold increase in the EAC volume, tumor growth inhibition, tumor growth index (TGI), and lifetime increase (LTI) in mice. A decrease in the TGI values and an increase in the LTI values occurred with increasing dose for all types of radiation. The relative biological effectiveness (RBE) value for helium ions determined by the area under the EAC growth dynamics curves reached a maximum value of 1.8 upon irradiation at the Bragg peak at a dose of 20 Gy.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207276","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":"Evidence for Functionality of Transmembrane Domains of Predicted Non-Canonical Plant Phosphotransmitters.","authors":"S N Lomin, E M Savelieva, A S Elanskaya, D V Arkhipov, G A Romanov","doi":"10.1134/S1607672925600381","DOIUrl":"https://doi.org/10.1134/S1607672925600381","url":null,"abstract":"<p><p>Bioinformatic methods have been used to predict a new subclass of proteins among plant phosphotransmitters involved in the signaling system of multistep phosphorelay. In contrast to the canonical soluble nucleocytosolic forms, the found noncanonical phosphotransmitter sequences, belonging to a wide range of plant taxa, potentially contain transmembrane domains. This suggests localization of such proteins on cell membranes and, therefore, a different function in signaling than that of canonical phosphotransmitters. We tested the functionality of the transmembrane domain of the phosphotransmitter using the protein of the tea plant Camellia sinensis. The membrane localization of the transiently expressed recombinant phosphotransmitter with this domain was confirmed by microscopy and immunoblotting. Thus, this is the first study to obtain experimental evidence for the existence of membrane-bound plant phosphotransmitters with as yet unknown functions. These data suggest the presence of a noncanonical membrane branch of signal transduction in the multistep phosphorelay system in plants.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207323","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":"Comparative Analysis of Nutritional and Biotechnological Value of Muscle Tissue of Mesopelagic Fishes of the North-East Atlantic Region.","authors":"V P Voronin, D V Artemenkov, A M Orlov, S A Murzina","doi":"10.1134/S1607672925600307","DOIUrl":"https://doi.org/10.1134/S1607672925600307","url":null,"abstract":"<p><p>A comparative analysis of some nutritional and biotechnological characteristics of muscle tissue of the most widespread and abundant mesopelagic fish species inhabiting the Irminger Sea (North Atlantic) was carried out. At the level of lipid metabolism, potential nutritional value was established for non-commercial Notoscopelus kroyeri and Serrivomer beanii along with the commercial beaked redfish Sebastes mentella. For Lampanyctus macdonaldi and, partially, Borostomias antarcticus, possible biotechnological value was shown in terms of extracting individual valuable molecules and substances of lipid nature. The other studied species (Bathylagus euryops, Chauliodus sloani, Malacosteus niger, Scopelogadus beanii, and Stomias boa), as well as B. antarcticus, are very promising for their use in aquaculture in the development of innovative feed compositions and additives for them. It was found that the depth and area of catch don't have a significant effect on the nutritional and biotechnological characteristics of the muscle tissue of the studied species. The exception is B. euryops, the characteristics under consideration of which vary depending on the area of catch; for S. mentella and S. beanii, on the depth of catch. The results of the study can serve as a basis for the development and improvement of methods and protocols for sustainable use of deep-sea biological resources in the process of their development in the North Atlantic region, as well as determine the areas of practical use of these species and the format of products obtained from them or with their use (feed, additive, pure substance, composition, functional food product, etc.).</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956410","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":"Assessment of the Damage Index and Its Dynamics in Patients with Non-Systemic Variants of Juvenile Arthritis during the Treatment with Biologics.","authors":"Z A Kolkhidova, I P Nikishina, S I Glukhova","doi":"10.1134/S1607672925700127","DOIUrl":"https://doi.org/10.1134/S1607672925700127","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Juvenile idiopathic arthritis (JIA) is characterized by a high risk of joint destruction, extra-articular changes, and rapidly progressive disability. The CHAQ (Childhood Health Assessment Questionnaire) and  X-ray are often used to assess functional impairment and the degree of irreversible damage, but both methods have limitations. The Juvenile Arthritis Damage Index (JADI) has been developed to comprehensively assess the biological prognosis of JIA, which includes articular (JADI-A) and extra-articular (JADI-E) damage evaluation. The use of the JADI may be an effective tool for predicting and monitoring the effectiveness of JIA therapy in real clinical practice conditions. THE AIM : of the study was to identify correlations of the JADI index with features of clinical manifestations in patients with non-systemic variants of JIA who had no experience with biologic therapy (B) and to evaluate the impact of lesions defined through the JADI damage index value on predicting response to B.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;. This open prospective study included 150 children with non-systemic JIA variants with no history of biologic therapy. The mean age was 12.2 ± 4.6 years, 60% were girls; 112 patients were examined in dynamics after 6 or 12 months from the beginning of therapy with biologics. Clinical and anamnestic evaluations, including detailed assessment of joint status and JADI-A and JADI-E scores, were performed on all patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;. The study showed that 50% of patients had damage on the JADI score, with 43% having JADI-A+ and 23% having JADI-E+. Both articular and extra-articular damage were present in 15% (n = 23) of children. Among those with JADI-A, flexion contractures of the knee joints were most frequently noted in 39%, elbow joints in 28%, and limitation of movement in the cervical spine in 26%. Extra-articular injuries were more frequently presented as avascular necrosis of bones, confirmed by imaging methods (41%), and a significant difference in limb length was observed in 35% of patients. The presence of articular changes was significantly associated with positivity for antinuclear antibody, rheumatoid factor, and anticyclic citrullinated peptide, as well as the absence of enthesitis, elevated erythrocyte sedimentation rate and С-reactive protein, high clinical activity, Juvenile Arthritis Disease Activity Score, CHAQ values, a history of glucocorticoid therapy, and low adherence to treatment. Polyarticular onset involving small hand joints and a tendency for rapid contracture formation were also associated with positive JADI-A values. The onset of polyarthritis with involvement of the small joints of the hands and a tendency to fast contracture formation were also associated with JADI-A positivity. As a result of therapy with biologics prescribed in routine clinical practice, the vast majority of patients achieved stable status without signs of damage or the value of the damage inde","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957716","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":"Analysis of Vβ-Segment Diversity of T-cell Receptor in Techa Riverside Residents Chronically Exposed to Radiation in the Long-Term Period.","authors":"A I Kotikova, E A Blinova, A V Akleyev","doi":"10.1134/S1607672925700164","DOIUrl":"https://doi.org/10.1134/S1607672925700164","url":null,"abstract":"<p><p>To study the repertoire of the T-cell receptor in chronically exposed persons in the long-term period. The study involved 48 people who were divided into two groups: a group of exposed persons (31 individuals with the mean accumulated dose to red bone marrow (RBM) of 981 ± 130 mGy) and a comparison group (17 individuals, the mean accumulated dose to RBM of 25.3 ± 5.91 mGy). The study groups did not differ significantly in age, gender, and ethnicity. The repertoire of Vβ-segments of the T-cell receptor of the peripheral blood T-lymphocytes of exposed persons was analyzed by flow cytometry method. 24 Vβ-segments of the T-cell receptor were studied. Statistical processing of the obtained data was carried out using the Wilcoxon signed-rank test, and a direct description of Vβ-segment repertoire of the T-cell receptor was performed using the Lorenz curve and the Gini-TCR index. The study revealed a statistically significant increase in the number of Vβ3 and Vβ5.2 T-cell receptor segments in exposed individuals relative to the comparison group (p = 0.03 and p = 0.003, respectively). It was also shown that the distribution of the Vβ-segments of the T-cell receptor was uneven in both study groups. However, there was no significant difference between the repertoires of the T-cell receptor of the studied groups by the Gini-TCR index (p = 0.14).</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954613","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":"Cognitive Impairments in Patients with Rheumatoid Arthritis and Comorbid Anxiety and Depressive Disorders: Outcomes of the Five-Year Prospective Study.","authors":"A A Abramkin, T A Lisitsyna, D Yu Veltishchev, O F Seravina, O B Kovleskaya, S I Glukhova, E L Nasonov","doi":"10.1134/S1607672925700061","DOIUrl":"https://doi.org/10.1134/S1607672925700061","url":null,"abstract":"<p><p>The aim of this study was to assess the baseline rates and five-years outcomes of mild cognitive impairments (MCIs) in patients with rheumatoid arthritis (RA) and comorbid anxiety and depressive disorders (ADDs) receiving traditional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone or in combination with biologic DMARDs (bDMARDs) and/or adequate psychopharmacotherapy (PPT), as well as to assess the factors associated with MCI after five years. A total of 128 RA patients were enrolled, ADDs were diagnosed in 123 (96.1%) patients by a licensed psychiatrist. Severity of depression and anxiety was evaluated with Montgomery-Asberg and Hamilton Anxiety scales. CIs were diagnosed during clinical and psychological examination using the battery of pathopsychological and projective techniques. CI outcomes were considered favourable in cases with no CI diagnosed throughout the study and in cases of CI reversal. PPT was offered, 52 (42.3%) patients agreed. Patients were  divided into the following treatment groups: сsDMARDs (n = 39), сsDMARDs + PPT (n = 43), сsDMARDs + bDMARDs (n = 32), and сsDMARDs + bDMARDs + PPT (n = 9). Multivariable logistic regression was performed to determine factors associated with CI after five years. MCIs were diagnosed in the majority of RA patients (73.2%), including logical thinking impairments (51.2%) and memory deficit (67.5%). At a 5-year endpoint, 74 patients were included. Total CI rates in no-PPT groups increased from 69 to 85.7% (p = 0.024) and was higher compared to PPT groups (р = 0.021, 85.7% vs 62.5%, RR 1.37). Patients with favourable CI outcomes had lower major depression prevalence and baseline Montgomery-Asberg scores, major improvement in depression symptoms, and higher rates of ADD remission after five years. Baseline DAS28 (OR 1.29, p < 0.001) was positively associated and remission of ADD negatively associated with MCI after five years (OR 0.25, p = 0.03), R² = 0.48, p < 0.001. ADDs and MCIs are highly prevalent in RA patients. While CIs tend to persist and worsen over time, PPT is associated with lower CI rates in long-term perspective. Personalized PPT with antidepressants and neuroleptics may show potential to lessen the rates of MCIs in RA patients with ADDs.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955011","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":"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":"https://doi.org/10.1134/S1607672925700139","url":null,"abstract":"&lt;p&gt;&lt;p&gt;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. MATERIALS AND METHODS: . 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. 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. RESULTS. : 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, p &gt; 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, p &lt; 0.05). 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%: p = 0.003 and p = 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 (r = 0.44, p &lt; 0.05), IL-17A and IL-23 (r = 0.40, p &lt; 0.05), IL-17F and IL-23 (r = 0.94, p &lt; 0.05) were found. 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. When IL-17A level was elevated, CDAI and SDAI indices and IgM RF concentration were significantly higher than in the comparison group (p &lt; 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 (p &lt; 0.05). At the same time, IL-17A concentration correlated with SDAI (r = 0.17, p &lt; 0.05), IgM RF values (r = 0.19, p &lt; 0.05), and ACCP (r = 0.19, p &lt; 0.05). When IL-23 values were high, the HR was significantly lower (28, p &lt; 0.05), and the groups did not differ in other indices of disease activity, IgM RF and ACCP. No differences in clinical and laboratory indices of RA activity were found between patients with simultaneous elevation of one, two, or three cytokines and groups of patients with their n","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"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}

{"title":"Thrombotic Antiphospholipid Syndrome: Recurrent Thromboses.","authors":"T M Reshetnyak, F A Cheldieva, S I Glukhova, K S Nurbaeva, N V Seredavkina, M V Cherkasova, A M Lila, E L Nasonov","doi":"10.1134/S1607672925700152","DOIUrl":"https://doi.org/10.1134/S1607672925700152","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Thrombotic antiphospholipid syndrome (APS) is a condition affecting young people in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;The aim of this study: &lt;/strong&gt;was to evaluate the incidence of recurrent thrombosis and its risk factors in antiphospholipid syndrome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;. The retrospective study included 98 patients with APS who were followed up at the institute from 2014 to 2023, of whom 66 (67%) were women and 32 (33%) were men. Of the 98 patients with APS, 48 (49%) had a diagnosis of systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL), including the antibodies to cardiolipin (IgG/IgM aCL), antibodies to ß2glycoprotein 1 (IgG/IgM aß2GP1), antibodies to ß2 glycoprotein IgG against domain 1 (IgG aß2GP1-D1), antibodies to phosphatidylserine/prothrombin complex (IgG/IgM aPS/PT), and other thrombotic risk factors were determined. aPL was assessed by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence assay (CLA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;: Thrombosis recurrence was reported in 62 (63%) of 98 patients, and in 36 (35%) it was not reported. The main cause of recurrent thrombosis was treatment with direct oral anticoagulants (DOACs). Twenty-four (38.7%) of  62 patients with recurrent thrombosis were treated with DOACs, the duration of which ranged from 6 to 24 months. The next most common cause of recurrent thrombosis was the lack of continuous anticoagulant therapy in 20 (32.5%) patients. In 17 (27.4%) patients, recurrence occurred while they were still taking warfarin. In 10 (41.7%) of the 24 patients, the recurrent thrombosis was arterial in origin. This was associated with recurrent cerebral circulation problems. The level of positivity for aPL did not matter, but all of them had triple IgG-aPL positivity. Five patients had lupus anticoagulant (LA) at the onset of the disease before anticoagulant therapy. IgG-aPS/PT was most important in association with recurring thrombosis in the ELISA: 45 (72.6%) of 62 patients with recurring thrombosis were positive for IgG-aPS/PT as compared with 19 (52.8%) of 36 patients without recurring thrombosis. The detection of all aPLs was more frequent in CLA than in ELISA. However, the determination of aPL by ELISA is recommended according to the latest classification criteria. Triple positivity for IgG aCL, IgG aß2GP1, and IgG aß2GP1-D1 according to CLA data remained a risk factor for recurrent thrombosis and increased the risk of recurrence more than 3 times. Obesity was a risk factor for recurrent thrombosis, with a 5-fold increased risk of recurrent thrombosis in obese patients compared to the non-obese ones (p = 0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;. Recurrent thrombosis in APS is largely associated with IgG aCL, IgG aß2GP1, IgG aß2GP1-D1, and IgG aPS/PT. Triple IgG aPL positivity in any combination significantly increased recurrent thrombosis risk. The pr","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956750","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":"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":"https://doi.org/10.1134/S1607672925700140","url":null,"abstract":"<p><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><strong>Materials and methods: </strong>. 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. 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><strong>Results: </strong>: 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 (p = 0.0012 and p = 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><strong>Conclusions: </strong>. 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":" ","pages":""},"PeriodicalIF":0.8,"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}

{"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":"https://doi.org/10.1134/S1607672925700073","url":null,"abstract":"<p><strong>Objective: </strong>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><strong>Materials and methods: </strong>: 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 (MX1, RSAD2, and EPSTI1) using real-time polymerase chain reaction.</p><p><strong>Results: </strong>. 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><strong>Conclusions: </strong>. 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":" ","pages":""},"PeriodicalIF":0.8,"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}