[Neutrophil extracellular traps in the pathogenesis of chronic rhinosinusitis]. / Neitrofil'nye vnekletochnye lovushki v patogeneze khronicheskogo rinosinusita.

The review presents the current understanding of the pathogenesis of chronic rhinosinusitis. The causes of damage to the mucous membrane of the paranasal sinuses are most often the result of a combination of immunological, infectious and anatomical factors. This indicates the need for a multidisciplinary approach to the study of the pathogenesis of this pathology. There is no single universally recognized classification of chronic rhinosinusitis, which takes into account histological and immunological changes in the mucous membrane of the paranasal sinuses. The discovery of the mechanism of completion of the life cycle of neutrophils - the formation of a neutrophil extracellular trap or NETosis, different from necrosis and apoptosis, opened up new prospects in the study of the pathogenesis of inflammatory processes, including rhinosinusitis. Neutrophil extracellular traps reduce the permeability of the epithelial barrier in the mucous membrane of the paranasal sinuses. This determines their possible role in the etiopathogenesis of rhinosinusitis. In recent years, more and more attention has been paid to the feasibility, effectiveness and safety of therapy that affects the immune component of the inflammatory process, including NETosis. The data obtained in the study of extracellular traps can be used in clinical practice. It is neutrophil extracellular traps that can become a potential target in the treatment of patients with chronic rhinosinusitis.

NETosis: Molecular Mechanisms, Role in Physiology and Pathology.

NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis. Induction of NETosis depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Activation of NADPH oxidase depends on increase in the concentration of Ca2+ in the cytoplasm and in some cases on the generation of ROS in mitochondria. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane. In this review, basic mechanisms of NETosis, as well as its role in the pathogenesis of some diseases including COVID-19 are discussed.

Neutrophil Extracellular Traps: New Aspects.

Neutrophils are the "first line" of defense against pathogens in the locus of inflammation, where they use effector functions such as phagocytosis, degranulation, and formation of reactive oxygen species (ROS). In 2004, Artuto Zychlinsky characterized one more neutrophil effector function-the release of neutrophil extracellular traps (or NETs). NETs are a modified chromatin "decorated" by bactericidal proteins of granules, nucleus, and cytoplasm. The release of NETs can be activated by diverse physiological and pharmacological stimuli and depends on ROS, for which NADPH oxidase is the main source. In the process of NET formation, the release of bactericidal components of granules into the cytoplasm, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope and cytoplasmic membrane with the involvement of gasdermin D protein, and, finally, the release of chromatin outside the cell occurs. At the same time, uncontrolled formation of NETs is a provoking factor in the development of many inflammatory and autoimmune diseases. NETs were found at autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and vasculitis; NETs are involved in the pathogenesis of cardiovascular, pulmonary, and oncological diseases. In this review, the main ideas about the mechanisms of NET formation, as well as their role in physiological processes and pathogenesis of a number of diseases (including COVID-19), are discussed.

Neutrophil extracellular traps: mechanisms of formation and role in health and disease.

Recent insights into the specific type of cell death characteristic of neutrophils, called NETosis, are summarized. NETosis is a process of generation of Neutrophil Extracellular Traps (NETs), whose main components are DNA, granular antimicrobial peptides, and nuclear and cytoplasmic proteins. The structure of NETs determines their bactericidal, fungicidal, antiprotozoal, and antiviral properties. Therefore, NETs production by neutrophils is an essential immune response to infection. In addition to the antimicrobial function, NETosis is involved in many inflammatory and autoimmune disorders and participates in the regulation of noninfectious processes. The molecular mechanisms of NET formation, bactericidal effect, and involvement in some noninfectious, autoimmune, and inflammatory processes are discussed in detail in this review.

Selective stimulation of the growth of anaerobic microflora in the human intestinal tract by electrolyzed reducing water.

96-99% of the "friendly" or residential microflora of intestinal tract of humans consists of strict anaerobes and only 1-4% of aerobes. Many diseases of the intestine are due to a disturbance in the balance of the microorganisms inhabiting the gut. The treatment of such diseases involves the restoration of the quantity and/or balance of residential microflora in the intestinal tract. It is known that aerobes and anaerobes grow at different oxidation-reduction potentials (ORP). The former require positive E(h) values up to +400 mV. Anaerobes do not grow unless the E(h) value is negative between -300 and -400 mV. In this work, it is suggested that prerequisite for the recovery and maintenance of obligatory anaerobic microflora in the intestinal tract is a negative ORP value of the intestinal milieu. Electrolyzed reducing water with E(h) values between 0 and -300 mV produced in electrolysis devices possesses this property. Drinking such water favours the growth of residential microflora in the gut. A sufficient array of data confirms this idea. However, most researchers explain the mechanism of its action by an antioxidant properties destined to detox the oxidants in the gut and other host tissues. Evidence is presented in favour of the hypothesis that the primary target for electrolyzed reducing water is the residential microflora in the gut.

Antimutagenicity of propionic acid bacteria.

The antimutagenic effect of dialysed cell extracts of 4 strains of propionic acid bacteria was examined against the mutagenicity of sodium azide in the TA1535 tester strain of Salmonella typhimurium using the Ames test. It was noted that dialysates of 2 strains of Propionibacterium shermanii, P. pentosaceum and P. acnes, significantly reduced sodium azide-induced revertants. The dialysate of propionic acid cocci did not show an antimutagenic effect. The inhibitory activity was enhanced if the mutagen and extract were coincubated for 20 min prior to performing the mutagenicity assay. Antimutagenicity of dialysates from P. shermanii VKM-103 against MNNG and 9-aminoacridine was shown in S. typhimurium strains TA1535 and TA97. The antimutagenic activity was found in the protein fraction of the cell extract of P. shermanii. The proteins of the dialysate of P. shermanii were separated using a Toyopearl gel column into 3 main peaks according to their molecular weights. The antimutagenic activity towards sodium azide was found in the second and the third peaks. We suggest that dialysates of the cells of propionic acid bacteria contain several kinds of antimutagenic substances with different molecular weights.