Влияние локального подавления экспрессии гена Stat3 на нейтрофильное воспаление легких в экспериментальной модели на мышах

Introduction. Promising sources of biologically active compounds (BAS) are extracts obtained from various morphological parts of plants of the numerous genus Astragalus L. One of the main groups of BAS isolated from plants of this genus are flavonoids, saponins, and polysaccharides. Sufficiently studied are Astragalus membranaceus (Fisch.) Bunge) and Astragalus mongholicus Bge., whose extracts have a wide range of pharmacological activity. Expansion of the nomenclature of medicinal plant materials and the study of BAS groups that determine the main pharmacological effects are topical studies in pharmacognosy. From this point of view, little-studied species of Astragalus (Astragalus henningii (Stev.) Klok., Astragalus testiculatus Pall., Astragalus varius S.G. Gmel., Astragalus dasyanthus Pall.), massively growing in the Volga region, are of interest.Aim. Isolation and identification of 5 aglycones of flavonoids in hydrolysates of water-alcohol extracts from Astragalus herb: A. henningii, A. testiculatus, A.varius, A. dasyanthus by HPLC/UV.Materials and methods. The objects of the study were the herb of four types of Astragalus (A. henningii, A. testiculatus, A.varius, A. dasyanthus), harvested during the period of mass flowering in the Saratov region and dried to an air-dry state. To study the composition of phenolic compounds, extraction was carried out with 70 % ethanol in the ratio of raw material : extracting agent 1 : 10 by infusion for 7 days. Acid hydrolysis was carried out with hydrochloric acid 37 % with heating for 40 min. The resulting hydrolysates were analyzed on an Agilent 1260 chromatograph (Agilent Technologies, USA) with a diode array detector, manual sample injection (Agilent G1328C manual injector, Agilent Technologies, USA) and an Agilent OpenLab CDS chromatographic data collection and processing system using an individually selected elution gradient of the mobile phase (0.1 % solution of orthophosphoric acids/acetonitrile). Compounds in the hydrolysates were identified by the retention times and UV spectra of a mixture of reference standards (RS) of quercetin, isorhamnetin, luteolin, kaempferol, and apigenin.Results and discussion. An elution gradient was selected for one time determination of 5 aglycones of flavonoids with a single analysis time of 13 minutes. These conditions made it possible to identify compounds in the hydrolyzates of water-alcohol extracts of four types of Astragalus. Luteolin, quercetin and apigenin were found in hydrolyzates of A. henningii, A. testiculatus and A. varius; isorhamnetin and kaempferol were found in A. henningii and A. varius. None of the analyzed aglycones was found in the A. dasyanthus hydrolyzate.Conclusion. After preliminary selection of the optimal conditions for the chromatographic separation of a mixture of 5 aglycones of flavonoids, hydrolysates of four types of Astragalus were analyzed. The data obtained indicate the prospects for further study of the chemical composition of Astragalus and confirm the expediency of their use for obtaining of new herbal remedies.

The paper presents a comprehensive view on the immunogenicity of botulinum toxin A products, analyzes the main causes of the immune response, its enhancing factors, and the further impact on the effectiveness of therapy. The overall statistics of resistance to various products both in clinical practice and when used in cosmetology are presented. The relationships between the composition of botulinum toxin A products, their immunogenicity, and the incidence of botulinum toxin resistance are evaluated; the main ways of overcoming it and minimizing the production of neutralizing antibodies are shown.

Background: We have recently reported the preclinical characterization of a recombinant birch pollen allergy vaccine based on a fusion protein, AB ‐ PreS , consisting of allergen‐derived peptides fused to the hepatitis B virus ( HBV )‐derived PreS surface protein as immunological carrier. Objective: To investigate in a clinical study the usefulness of the AB ‐ PreS vaccine, termed GNR ‐127, for allergen‐specific immunotherapy of birch pollen allergy. Methods: Stage 1 of the study, an open‐label Phase I study, determined among three doses (20 μg: n = 6; 40 μg: n = 6; 80 μg: n = 6) administered as Aluminum‐hydroxide‐adsorbed vaccines subcutaneously five times in monthly intervals, the highest tolerated doses. In the following Stage 2, randomized patients (placebo: n = 45; 40 μg: n = 43; 80 μg: n = 44) received in a single‐blind, placebo‐controlled Phase II study monthly up to five pre‐seasonal injections. Safety monitoring followed the Medical Dictionary for Regulatory Activities (MedDRA); efficacy parameters were determined according to the European Academy for Allergy and Clinical Immunology ( EAACI ) guidelines; allergen‐specific antibodies and basophil sensitivity were determined by ELISA and basophil activation testing, respectively. Results: A dose‐dependent reduction of the combined symptom medication score ( CSMS ) (40 μg: 17.41%; 80 μg: 24.13%) over placebo was observed which was significant for the 80 μg group and accompanied by the strongest induction of Bet v 1‐specific IgG (median 20‐fold increase) and a blunting of the seasonally boosted IgE response and basophil sensitivity. The vaccine showed an acceptable safety profile despite high administered doses. Conclusion: A pre‐seasonal course of 5 monthly injections of GNR ‐127 80 μg improved symptoms of birch pollen allergy accompanied by a robust Bet v 1‐specific IgG response, paving the road for a Phase III efficacy study. Trial Registration: ClinicalTrials.gov (Identifier: NCT07155499)

МИР19® — первый отечественный миРНК-препарат, лиофилизат для приготовления раствора для ингаляций для терапии COVID-19, в комплекте с растворителем. Лекарственное средство содержит действующее вещество – синтетическую малую интерферирующую РНК siRk-12 (миРНК) и вспомогательное вещество — катионный дендримерный пептид KK-46 в массовом соотношении 1/20. В настоящей статье описываются методы и разработанные методики стандартизации и контроля качества вспомогательного вещества терапевтического олигонуклеотидного препарата, которые вошли в спецификацию на лекарственный препарат МИР19® и были использованы для регистрации в РФ.

Ragweed (Ambrosia artemisiifolia) pollen allergy is a major and growing public health problem worldwide, with clinical manifestations ranging from rhinitis and conjunctivitis to asthmatic episodes and anaphylaxis. The major ragweed allergen, Amb a 1, exhibits high IgE-binding potential and triggers type 1 hypersensitivity reactions. Although allergen-specific immunotherapy (AIT) effectively induces long-term immune tolerance, conventional extract-based formulations face critical limitations including batch-to-batch variability, heterogeneous allergen composition, IgE-mediated adverse reactions, inconsistent immunogenicity, and poor patient compliance. This critical review synthesizes and evaluates published evidence on current synthetic vaccine strategies for ragweed AIT, with emphasis on their design, immunological performance, and quality control considerations. This review critically evaluates current approaches to synthetic vaccine development for ragweed AIT, with a particular focus on peptide-based constructs, recombinant proteins, DNA vaccines, and adjuvant-enhanced formulations, alongside corresponding quality control strategies. The available evidence indicates that synthetic vaccines provide a more rational, molecularly characterized trajectory for producing optimized AIT products with improved safety profiles, enhanced clinical efficacy, reduced injection frequency, and improved batch standardization relative to extract-based immunotherapy. These advances highlight the potential of synthetic vaccine platforms to support personalized immunotherapy and more effective disease-modifying treatment of allergic disorders.