German Youth Language: Word-Formation Types of Suffix Nouns and Their Semantic Relations

The article is devoted to the study of word-formation types in modern German youth slang and a description of their systemic paradigmatic relations. The research material was a large group of suffix nouns, presented in the dictionaries of youth slang, as well as on youth literature sites. The suffix nouns formed by the word-formation type “producing basis + suffix” are analyzed in the article. The deep connections of motivating and motivated units are revealed, which reflect the logic of the connections of objects of reality in the linguistic consciousness, and the implementation of these relations in word-formation types is also traced. As a result of the analysis of word-formation meanings in the group of German nouns, which are youth slangisms constructed according to the “base + suffix” model, 4 main word-formation types were identified. The analysis proves that the thematic associations of the same word-formation type are in a variety of paradigmatic relationships, which at the lexical level are manifested in the form of synonymy, hypo- and hyperonymy, antonymy and polysemy. The word-formation types of suffix nouns studied in this work allowed to conclude that the intra-type and inter-type semantic relations are manifested most variably in the lexical-semantic field “Human designation”

Peptides of the innate immunity as potential anticancer agents: pros and cons

Surgical resection was the main approach to cancer therapy, often supplemented by radiation and chemotherapy. The effectiveness of such complex treatment in many cases remains low. In this regard, there is an urgent need to search for new compounds that have selective cytotoxic activity against tumor cells and do not damage normal tissues of the organism. The review discusses mechanisms of antitumor action of cationic antimicrobial peptides (AMPs) of the cathelicidin family - human α-helical cathelicidin (LL-37), and a peptide with β-hairpin conformation – protegrin-1 (PG-1) on lung, breast, pancreas, prostate, squamous skin cancer cells, oral cancer, stomach, ovarian, colorectal cancer, melanoma, leukemia, lymphoma, glioma and neuroblastoma cells. An opportunity of antitumor and pro-oncogenic actions of the peptides and an interplay of these effects with mmunomodulatory action of AMPs on tumor-associated macrophages, natural killer cells and T-lymphocytes is discussed. Possible mechanisms of LL-37 and PG-1 selective action upon tumor cells are presented, including the interaction of LL-37 with G-protein-coupled receptors: the N formylpeptide-2 receptor (FPR2), CXC chemokine-2 (CXCR2), Mas-related gene X2 (MrgX2), purinergic (P2Y11), epidermal (EGFR/ErbB1, ERBb2), insulin-like (IGF1R) growth factors, ligand-gated ion channels (LGIC) and Tolllike (TLR) receptors, with expression varying significantly in different types of tumors, as compared to normal tissues. An increase in the level of LL-37 secretion and expression of its CAMP gene are associated with progression of lung adenocarcinoma, breast, pancreas, and prostate cancer, ovarian cancer, melanoma, and squamous cell carcinoma of the skin. In contrast, CAMP expression and LL-37 secretion are significantly reduced in gastric cancer cells, oral squamous cell cancer, colorectal cancer, leukemia, lymphomas, gliomas, and SH-SY5Y neuroblastoma. Therefore, therapeutic effects of LL-37 can only be used for specific types of tumors. The mechanisms of action of PG-1 on tumor cells are still poorly understood, although the available data indicate that protegrin exhibits a more unidirectional effect, i.e., it damages cell membranes. Protegrin-1 and LL-37 can synergistically enhance the antitumor effects of chemotherapy drugs and have a more pronounced effect on tumor cells, than upon normal cells. Natural AMPs appear to be promising candidates for the role of new antitumor agents, which are also active against malignant metastatic, recurrent multidrug-resistant tumors. On the other hand, peptides such as LL-37, in some cases, exhibit properties that can be considered pro-oncogenic, which indicates a need for further detailed studies on the molecular mechanisms of their action on tumor cells

Immunomodulatory and neurotropic activities of synthetic peptides in a model of brain injury in rats

Treatment of consequences of traumatic brain injury (TBI) remains one of the current problems of medicine. To increase the effectiveness of treatment of post-traumatic complications, various drugs are recommended, including the peptide with neuromodulatory activity Semax.The present study aims to determine the presence of neuro- and immunoprotective properties of the synthetic peptide PR5, composed of fragments of proline-rich antimicrobial peptides.The work was performed on male Wistar rats weighing 300-350 g. The “falling weight” model of mechanical brain injury was used, which mainly causes diffuse brain damage. The synthesized peptide PR5, composed of fragments of known proline-rich peptides of animal neutrophils, and the peptide preparation Semax in the form of a 1% aqueous solution were used. The drugs were administered intranasally 1 hour after TBI, then twice a day for 4 days at a dose of 100 mg/kg body weight. Control animals received physiological saline in the same regimen as the peptide preparations.TBI led to a significant decrease in body weight, but in rats receiving the peptide preparation Semax, the decrease in body weight was significantly less than in control animals, and the PR5 preparation completely prevented the decrease in body weight after TBI. After TBI, the proliferative activity of lymphocytes was suppressed and the cytotoxicity of NK cells decreased. In animals treated with peptide preparations, there was no significant suppression of NK cell cytotoxicity, and the proliferative activity of lymphocytes was restored to the level of control animals by day 14 after TBI. Both peptide preparations used contributed to higher locomotor activity, and in animals treated with the PR5 peptide, this type of activity reached the parameters of control animals. The reduction in freezing duration in groups treated with peptide preparations indicates the presence of a sedative effect.The peptide preparation PR5 was active in this series of experiments, showing immunotropic and neuroprotective activity comparable to the Semax preparation. Further studies aimed at confirming the identified types of activity of the peptide preparation PR5 may justify its prospects for clinical use as a new nootropic agent

FEATURES OF IMMUNE RESPONSE IN PRETERM BABIES WITH BRONCHOPULMONARY DISPLASIA OF VARIOUS SEVERITY

To evaluate the immunity indexes in the children who were born with bronchopulmonary dysplasia (BPD) of varying severity at very early delivery terms (22-27 weeks), dynamic examinations were performed in 35 infants: 17 children were with severe BPD; 18, with mild-severity and moderately severe BPD. The comparison group consisted of seven children born at 22-27 weeks of gestational age without signs of BPD. Relative numbers of lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, CD16+CD56+, CD4+CD25+), and monocytes (CD14+CD64+, CD14+HLA-DR+) were determined by flow cytometry. The level of cytokines (IL-6, IL-8, IL-4) was measured by enzyme immunoassay technique. The features of immune status in children with BPD of severe, mild and moderate severity were discerned. It was found that the predictors of severe BPD development in the children born at very early terms, are: increased content of IL-8 at birth and at the age of 1 month, reduced level of expression on monocytes (CD64, HLA-DR) on the 1 month of life, and CD14+CD64+ cells at 38-40 weeks post conception. The revealed features of immune status in newborns with BPD can be used to assess the effectiveness of the therapy, which requires further research in this direction

A clinical case of genetically confirmed myotubular myopathy

The aim of the study - presentation of a clinical case of genetically confirmed myotubular myopathy.Цель исследования – представление клинического случая генетически подтвержденной миотубулярной миопатии

РЕГУЛЯЦИЯ МИЕЛОПЕРОКСИДАЗОЙ СA2+-СИГНАЛИЗАЦИИ В НЕЙТРОФИЛАХ

It is shown that myeloperoxidase (MPO) initiates an increase in the concentration of intracellular free calcium ions in neutrophils caused both by the release of calcium ions from intracellular stores, and extracellular Ca2+ entry across the plasma membrane channels. It is found that MPO modified by hypohalous acids retains its ability to induce Ca2+-signaling in neutrophils. It is established that MPO-induced entry of Ca2+ into cytosol of neutrophils is not associated with its catalytic activity, but caused by direct binding of MPO to α-subunit of β2-integrin of neutrophils and tyrosine kinase activation.Показано, что миелопероксидаза (МПО) инициирует увеличение концентрации свободных ионов внутриклеточного кальция в нейтрофилах, обусловленное как выходом ионов кальция из внутриклеточных депо, так и входом внеклеточного Са2+ через каналы плазматической мембраны. Установлено, что модифицированная гипогалоидными кислотами МПО сохраняет свою способность инициировать Са2+-сигнализацию в нейтрофилах. МПО-индуцированный вход Са2+ в цитозоль нейтрофилов не связан с проявлением каталитической активности фермента, а обусловлен непосредственным связыванием МПО с α-субъединицей β2-интегрина нейтрофилов и активацией тирозинкиназ

The phenomenon of multidrug resistance in glioblastomas

The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresistance and chemoresistance. In the current review, we discuss the phenomenon of multidrug resistance of GBM in the context of the expression of ABC family transporter proteins and the mechanisms of proliferation, angiogenesis, and recurrence. We focused on the search of molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes, and their single-nucleotide polymorphisms

Human antimicrobial peptides in autoimmunity

Antimicrobial peptides (AMPs) were firstly discovered as cytotoxic substances that killed bacteria. Later they were described as biologically active peptides that are able not only to kill invaders but also to modulate host immunity. In particular, it is shown that human antimicrobial peptides are able to influence the activity of different innate and adaptive immunity components, thus, obviously, they also participate in autoimmune processes. In this review we discuss the nature of human AMPs and analyze their role in such autoimmune disorders like type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and sarcoidosis. These peptides were shown to have a “double-sided” influence on the autoimmune disease pathogenesis. Thus, described facts should be taken into account for the development of new pharmaceutical agents to cure patients with autoimmune disorders. These agents could derive from natural antimicrobial peptides that in some cases modulate immune response. For example, it was shown that human AMPs are able to modulate complement system dysregulation of which is known to be one of the most dangerous pathogenic factors during autoimmune processes

Two Novel Lytic Bacteriophages Infecting <i>Enterococcus</i> spp. Are Promising Candidates for Targeted Antibacterial Therapy

The rapid emergence of antibiotic resistance is of major concern globally. Among the most worrying pathogenic bacteria are vancomycin-resistant enterococci. Phage therapy is a highly promising method for controlling enterococcal infections. In this study, we described two virulent tailed bacteriophages possessing lytic activity against Enterococcus faecalis and E. faecium isolates. The SSsP-1 bacteriophage belonged to the Saphexavirus genus of the Siphoviridae family, and the GVEsP-1 bacteriophage belonged to the Schiekvirus genus of Herelleviridae. The genomes of both viruses carried putative components of anti-CRISPR systems and did not contain known genes coding for antibiotic-resistance determinants and virulence factors. The conservative arrangement of protein-coding sequences in Saphexavirus and Schiekvirus genomes taken together with positive results of treating enterococcal peritonitis in an animal infection model imply the potential suitability of GVEsP-1 and SSsP-1 bacteriophages for clinical applications

Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci.

Human beta-defensin 3 (hBD3) is a highly charged (+11) cationic host defense peptide, produced by epithelial cells and neutrophils. hBD3 retains antimicrobial activity against a broad range of pathogens, including multiresistant Staphylococcus aureus, even under high-salt conditions. Whereas antimicrobial host defense peptides are assumed to act by permeabilizing cell membranes, the transcriptional response pattern of hBD3-treated staphylococcal cells resembled that of vancomycin-treated cells (V. Sass, U. Pag, A. Tossi, G. Bierbaum, and H. G. Sahl, Int. J. Med. Microbiol. 298:619-633, 2008) and suggested that inhibition of cell wall biosynthesis is a major component of the killing process. hBD3-treated cells, inspected by transmission electron microscopy, showed localized protrusions of cytoplasmic contents, and analysis of the intracellular pool of nucleotide-activated cell wall precursors demonstrated accumulation of the final soluble precursor, UDP-MurNAc-pentapeptide. Accumulation is typically induced by antibiotics that inhibit membrane-bound steps of cell wall biosynthesis and also demonstrates that hBD3 does not impair the biosynthetic capacity of cells and does not cause gross leakage of small cytoplasmic compounds. In in vitro assays of individual membrane-associated cell wall biosynthesis reactions (MraY, MurG, FemX, and penicillin-binding protein 2 [PBP2]), hBD3 inhibited those enzymes which use the bactoprenol-bound cell wall building block lipid II as a substrate; quantitative analysis suggested that hBD3 may stoichiometrically bind to lipid II. We report that binding of hBD3 to defined, lipid II-rich sites of cell wall biosynthesis may lead to perturbation of the biosynthesis machinery, resulting in localized lesions in the cell wall as demonstrated by electron microscopy. The lesions may then allow for osmotic rupture of cells when defensins are tested under low-salt conditions