Skin burns and ulcers are considered hard-to-heal wounds due to their high infection risk. For this reason, designing new options for wound dressings is a growing need. The objective of this work is to investigate the properties of poly (ε-caprolactone)/poly (vinyl-pyrrolidone) (PCL/PVP) microfibers produced via electrospinning along with sorbents loaded with Argovit™ silver nanoparticles (Ag-Si/Al₂O₃) as constituent components for composite wound dressings. The physicochemical properties of the fibers and sorbents were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma optical emission spectroscopy (ICP-OES). The mechanical properties of the fibers were also evaluated. The results of this work showed that the tested fibrous scaffolds have melting temperatures suitable for wound dressings design (58–60 °C). In addition, they demonstrated to be stable even after seven days in physiological solution, showing no macroscopic damage due to PVP release at the microscopic scale. Pelletized sorbents with the higher particle size demonstrated to have the best water uptake capabilities. Both, fibers and sorbents showed antimicrobial activity against Gram-negative bacteria Pseudomona aeruginosa and Escherichia coli, Gram-positive Staphylococcus aureus and the fungus Candida albicans. The best physicochemical properties were obtained with a scaffold produced with a PCL/PVP ratio of 85:15, this polymeric scaffold demonstrated the most antimicrobial activity without affecting the cell viability of human fibroblast. Pelletized Ag/Si-Al₂O₃-3 sorbent possessed the best water uptake capability and the higher antimicrobial activity, over time between all the sorbents tested. The combination of PCL/PVP 85:15 microfibers with the chosen Ag/Si-Al₂O₃-3 sorbent will be used in the following work for creation of wound dressings possessing exudate retention, biocompatibility and antimicrobial activity.

Nucleic acid aptamers capable of affine and specific binding to their molecular targets have now established themselves as a very promising alternative to monoclonal antibodies for diagnostic and therapeutic applications. Although the main focus in aptamers’ research and development for biomedicine is made on cardiovascular, infectious, and malignant diseases, the use of aptamers as therapeutic or diagnostic tools in the context of rheumatic diseases is no less important. In this review, we consider the main features of aptamers that make them valuable molecular tools for rheumatologists, and summarize the studies on the selection and application of aptamers for protein biomarkers associated with rheumatic diseases. We discuss the progress in the development of aptamer-based diagnostic assays and targeted therapeutics for rheumatic disorders, future prospects in the field, and issues that have yet to be addressed.

The aim – to evaluate the clinical effectiveness, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of seniprutug (BCD-180) in patients with radiographic active axial spondyloarthritis (r-axSpA, or ankylosing spondylitis).Subjects and methods. 260 patients with active r-axSpA and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs) were randomized into three groups: seniprutug (BCD-180) at doses of 5 mg/kg or 7 mg/kg, or placebo. BCD-180 was administered on weeks 0–12–36. Patients in the placebo group were switched to BCD-180 at a dose of 5 mg/kg at week 24 and continued therapy at week 36. The primary endpoint was the proportion of patients achieving 40% improvement by Assessment in Spondyloarthritis International Society scale (ASAS40) at week 24. Secondary endpoints were proportion achieving ASAS20/40, improvement of 5 out of 6 criteria of ASAS (ASAS5/6), ASAS partial remission, clinically important improvement in ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) (ASDAS-CII) and major improvement in ASDAS-CRP (ASDAS-MI). The dynamics of the disease activity status according to ASDAS-CRP, the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) indices, as well as the dynamics of laboratory markers (C-reactive protein anderythrocyte sedimentation rate (ESR)) were analyzed. Safety was assessed by the frequency and profile of adverse events (AEs) and adverse reactions (ARs).Results. The proportion of patients achieving ASAS40 at week 24 with seniprutug (BCD-180) at the dose of 7 mg/kg 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 in patients with r-axSpA, BCD-180 at both study doses was significantly superior to placebo at week 24 in the following measures: decrease in the proportion of subjects with very high disease activity (ASDAS-CRP>3.5) achieving ASDAS-CII, ASAS20, ASAS5/6. A statistically significant decrease in the ASDAS-CRP, BASDAI, BASFI indices, as well as the concentration of CRP and ESR were demonstrated. Tolerability of seniprutug therapy was assessed as acceptable. Infusion reactions were the most common observed adverse events, the vast majority of which were mild to moderate in severity according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events) and developed predominantly during the first administration. The proportion of patients with binding antibodies was 5.1%. However, no neutralizing antibodies were detected.Conclusion. Seniprutug (BCD-180) demonstrated superiority over placebo in clinical efficacy with a favorable safety profile and low immunogenicity as a treatment of r-axSpA.

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory rheumatic diseases with a predilection for the spinal and sacroiliac joints, which include axial spondyloarthritis, psoriatic arthritis, reactive arthritis, arthritis associated with chronic inflammatory bowel disease, and undifferentiated spondyloarthritis. The prevalence of SpA in the population varies from 0.5 to 2%, most commonly affecting young people. Spondyloarthritis pathogenesis is related to the hyperproduction of proinflammatory cytokines (TNFα, IL-17A, IL-23, etc.). IL-17A plays a key role in the pathogenesis of spondyloarthritis (inflammation maintenance, syndesmophites formation and radiographic progression, enthesites and anterior uveitis development, etc.). Targeted anti-IL17 therapies have established themselves as the most efficient therapies in SpA treatment. The present review summarizes literature data on the role of the IL-17 family in the pathogenesis of SpA and analyzes existing therapeutic strategies for IL-17 suppression with monoclonal antibodies and Janus kinase inhibitors. We also consider alternative targeted strategies, such as the use of other small-molecule inhibitors, therapeutic nucleic acids, or affibodies. We discuss advantages and pitfalls of these approaches and the future prospects of each method.

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). . 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). 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. . 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.

Osteoporosis is becoming a “silent pandemic” because of its ever-increasing prevalence and the absence of clinical manifestations until a bone fracture happens. The purpose of this review is to summarize the actual data on the pathogenesis of osteoporosis and its treatment options. The disease develops through a multifactorial process involving an imbalance between bone remodeling and different factors like genetics, non-coding RNA regulation, osteoimmune dysregulation, oxidative stress, cellular senescence, and fat–bone interactions. Existing medications have beneficial effects by preserving and increasing bone density and reducing the risk of fractures. Among them, there are bisphosphonates, strontium ranelate, calcitonin, estrogen-progestin therapy, selective estrogen receptor modulators, and parathyroid hormone analogues. Otherwise, they suffer from certain disadvantages, such as adverse effects, including serious ones, and limitations associated with comorbidity. Targeting pathways underlying bone metabolism could significantly improve the therapeutic options and provide new tools in the fight against osteoporosis. We consider here targeted therapeutics that are already in clinical practice, as well as the most promising novel agents that are now under development: antibodies, siRNAs, aptamers, and small molecules.