The Impact of Adjuvanted and Non-Adjuvanted Influenza Vaccines on the Innate and Adaptive Immunity Effectors

To date, the advantage of adjuvanted over non-adjuvanted vaccines in the specific antibodies formation is proved. However, cellular mechanisms, including parameters of the innate immunity, involved in the vaccine-induced immune response are not well studied. The human study of inactivated vaccines showed that both subunit vaccine and split vaccine induced cellular immune response, but adjuvanted vaccine containing Polyoxidonium had the greatest potential. Despite the fact that influenza vaccines must activate endosomal receptors, they cause non-specific activation of the surface TLRs. They can trigger intracellular signals leading to the induction of antiviral mechanisms and to the activation of the body’s protective resources against microbial infections. To assess the immunological efficacy of adjuvanted vaccines and humoral reactions to vaccination it is necessary to evaluate activation of cellular mechanisms of innate and adaptive immunity

Hybrid Principles in the Novel “Steamship to Argentina” by Alexei Makushinsky

Цель настоящей статьи — исследовать роман Алексея Макушинского «Пароход в Аргентину» (2014) с позиций теории гибридности. Эта одна из наиболее популярных на сегодняшний день концепций рассматривается в бахтинской интерпретации, где гибридные свойства романа напрямую связаны с его полифонизмом. Ключевым теоретическим основанием работы выступает термин Михаила Бахтина «гибридная конструкция», благодаря чему «Пароход в Аргентину» предстает в виде диалога и спора голосов двух главных героев — архитектора и писателя. Исследуя эти голоса и особенности их взаимодействия в пределах отдельных грамматических высказываний, мы приходим к мысли, что этот вид разноречия связан со стилистическими, смыслообразующими особенностями текста и имеет прямой выход на формальные моменты организации романа. В частности, именно он позволяет наиболее продуктивно рассмотреть особый авторский синтаксис, для обозначения которого мы вводим термин «архитектурное письмо». В статье были использованы следующие методы: сравнительно-сопоставительный (в работе с теоретическими источниками), описательный и метод структурного анализа, которые позволили выявить гибридные конструкции и проследить их связи с идейно-тематическим, смысловым и формальным уровнями текста. Полученные результаты могут быть перспективны для более глубокого изучения творчества Алексея Макушинского, а также в исследованиях идиостиля и эстетической уникальности романов других современных . This paper aims to investigate the novel “Steamship to Argentina” by Aleksei Makushinsky (2014) from the standpoint of hybrid theory. The key theoretical basis of the work is Mikhail Bakhtin’s term “hybrid construction” which is directly related to the polyphonic nature of the novel genre. From this position, the novel appears as a dialogue of voices and languages of the two main characters: the architect and the writer. The authors explore these voices and their interaction within specific grammatical utterances and conclude that they are linked to the stylistic features of the text and its formal properties. To describe Makushinsky’s unconventional syntax, the authors of this article introduce the term “architectural writing”. The obtained results can be used for a deeper study of Aleksey Makushinsky’s creativity, as well as in studies of the idiostyle and aesthetic uniqueness of novels by other contemporary authors

Targeting of FGF-Signaling Re-Sensitizes Gastrointestinal Stromal Tumors (GIST) to Imatinib In Vitro and In Vivo

Dysregulation of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling pathway is frequently observed in multiple human malignancies, and thus, therapeutic strategies targeting FGFs and FGFRs in human cancer are being extensively explored. We observed the activation of the FGF/FGFR-signaling pathway in imatinib (IM)-resistant gastrointestinal stromal tumor (GIST) cells. Furthermore, we found that the activation of FGFR signaling has a significant impact on IM resistance in GISTs in vitro. Next, we tested the efficacy of BGJ398, a potent and selective FGFR1–3 inhibitor, in xenograft models of GISTs exhibiting secondary IM resistance due to receptor-tyrosine kinase (RTK) switch (loss of c-KIT/gain of FGFR2a). Five to eight-week-old female nu/nu mice were subcutaneously inoculated into the flank areas with GIST T-1R cells. Mice were randomized as control (untreated), IM, BGJ398, or a combination and treated orally for 12 days. IM had a moderate effect on tumor size, thus revealing GIST resistance to IM. Similarly, a minor regression in tumor size was observed in BGJ398-treated mice. Strikingly, a 90% decrease in tumor size was observed in mice treated with a combination of IM and BGJ398. Treatment with BGJ398 and IM also induced major histopathologic changes according to a previously defined histopathologic response score and resulted in massive myxoid degeneration. This was associated with increased intratumoral apoptosis as detected by immunohistochemical staining for cleaved caspase-3 on day 5 of the treatment. Furthermore, treatment with BGJ398 and IM significantly reduced the proliferative activity of tumor cells as measured by positivity for Ki-67 staining. In conclusion, inhibition of FGFR signaling substantially inhibited the growth of IM-resistant GISTs in vitro and showed potent antitumor activity in an IM-resistant GIST model via the inhibition of proliferation, tumor growth, and the induction of apoptosis, thereby suggesting that patients with advanced and metastatic GISTs exhibiting IM resistance might benefit from therapeutic inhibition of FGFR signaling

Mucosal immunity in health care workers’ respiratory tracts in the post-COVID-19 period

Abstract Coronavirus disease (COVID-19) has generated interest in the assessment of systemic immune status, but existing knowledge about mucosal immunity is clearly insufficient to understand the full pathogenetic mechanisms of the disease. The aim of this study was to evaluate the long-term effects of novel coronavirus infection on mucosal immunity in the postinfection period among health care workers (HCWs). A total of 180 health care workers with and without a history of COVID-19 who ranged in age from 18 to 65 years were enrolled in this one-stage, cross-sectional study. The study subjects completed the 36-Item Short Form (36) Health Survey (SF-36) and the Fatigue Assessment Scale. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, and nasopharyngeal and oropharyngeal scrapings by an enzyme-linked immunosorbent assay. Specific anti-SARS-CoV-2 IgG antibodies were quantified in serum samples by chemiluminescence immunoassay. Analysis of the questionnaire data showed that all HCWs with a history of COVID-19 reported health problems that limited their daily activities and negative changes in their emotional health three months after the disease, regardless of its severity. The following shifts were detected in the adaptive arm of the immune response in different mucosal compartments. Among subjects who had severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). Compared to the subjects in the control group, all subjects with prior COVID-19 had significantly higher levels of total IgG in induced sputum. In the group of patients who had had severe infection, total IgG in saliva was also higher (p < 0.05). A direct statistically significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. A significant correlation was observed between total IgG levels and the parameters of physical and social activities, mental health, and fatigue levels. Our study demonstrated long-term changes in the humoral mucosal immune response, which were most pronounced in health care workers with a history of severe or moderate-to-severe COVID-19, and an association of these changes with certain clinical signs of post-COVID-19 syndrome

Pyrochlore-Group Minerals in the Granite-Hosted Katugin Rare-Metal Deposit, Transbaikalia, Russia

Pyrochlore group minerals are the main raw phases in granitic rocks of the Katugin complex-ore deposit that stores Nb, Ta, Y, REE, U, Th, Zr, and cryolite. There are three main types: Primary magmatic, early postmagmatic (secondary-I), and late hydrothermal (secondary-II) pyrochlores. The primary magmatic phase is fluornatropyrochlore, which has high concentrations of Na2O (to 10.5 wt.%), F (to 5.4 wt.%), and REE2O3 (to 17.3 wt.%) but also low CaO (0.6&ndash;4.3 wt.%), UO2 (to 2.6 wt.%), ThO2 (to 1.8 wt.%), and PbO (to 1.4 wt.%). Pyrochlore of this type is very rare in nature and is limited to a few occurrences: Rare-metal deposits of Nechalacho in syenite and nepheline syenite (Canada) and Mariupol in nepheline syenite (Ukraine). It may have crystallized synchronously with or slightly later than melanocratic minerals (aegirine, biotite, and arfvedsonite) at the late magmatic stage when Fe from the melt became bound, which hindered the crystallization of columbite. Secondary-I pyrochlore follows cracks or replaces primary pyrochlore in grain rims and is compositionally similar to the early phase, except for lower Na2O concentrations (2.8 wt.%), relatively low F (4 wt.%), and less complete A- and Y-sites occupancy. Secondary-II pyrochlore is a product of late hydrothermal alteration, which postdated the formation of the Katugin deposit. It differs in large ranges of elements and contains minor K, Ba, Pb, Fe, and significant Si concentrations but also low Na and F. Its composition mostly falls within the field of hydro- and keno-pyrochlore

Imbalance between Actin Isoforms Contributes to Tumour Progression in Taxol-Resistant Triple-Negative Breast Cancer Cells

The widespread occurrence of breast cancer and its propensity to develop drug resistance highlight the need for a comprehensive understanding of the molecular mechanisms involved. This study investigates the intricate pathways associated with secondary resistance to taxol in triple-negative breast cancer (TNBC) cells, with a particular focus on the changes observed in the cytoplasmic actin isoforms. By studying a taxol-resistant TNBC cell line, we revealed a shift between actin isoforms towards γ-actin predominance, accompanied by increased motility and invasive properties. This was associated with altered tubulin isotype expression and reorganisation of the microtubule system. In addition, we have shown that taxol-resistant TNBC cells underwent epithelial-to-mesenchymal transition (EMT), as evidenced by Twist1-mediated downregulation of E-cadherin expression and increased nuclear translocation of β-catenin. The RNA profiling analysis revealed that taxol-resistant cells exhibited significantly increased positive regulation of cell migration, hormone response, cell–substrate adhesion, and actin filament-based processes compared with naïve TNBC cells. Notably, taxol-resistant cells exhibited a reduced proliferation rate, which was associated with an increased invasiveness in vitro and in vivo, revealing a complex interplay between proliferative and metastatic potential. This study suggests that prolonged exposure to taxol and acquisition of taxol resistance may lead to pro-metastatic changes in the TNBC cell line

Secretory IgA and course of COVID-19 in patients receiving a bacteria-based immunostimulant agent in addition to background therapy

Abstract Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA) might contribute to the activation of the immune response mechanisms. To assess the levels of sIgA produced by epithelial cells in the nasal and pharyngeal mucosa and those measured in salivary gland secretions and to study the course of COVID-19 following the combined scheme of intranasal and subcutaneous administration of a bacteria-based immunostimulant agent. This study included 69 patients, aged between 18 and 60, who had moderate COVID-19 infection. They were divided into two groups: Group 1 (control group) included 39 patients who received only background therapy, and Group 2 was made up of 30 patients who received background therapy in combination with the Immunovac VP4 vaccine, a bacteria-based immunostimulant agent, which was given for 11 days starting from the day of admission to hospital. The levels of sIgA were measured by ELISA in epithelial, nasal and pharyngeal swabs, and salivary gland secretions at baseline and on days 14 and 30. The combined scheme of intranasal and subcutaneous administration of the Immunovac VP4 vaccine in the complex therapy of patients with COVID-19 is accompanied by increased synthesis of sIgA in nasal and pharyngeal swabs, more intense decrease in the level of C-reactive protein (CRP) and reduction in the duration of fever and length of hospitalization compared to the control group. Prescribing a immunostimulant agent containing bacterial ligands in complex therapy for COVID-19 patients helps to enhance mucosal immunity and improves the course of the disease