[Effect of microand nanoplastics on the gastrointestinal mucosa and intestinal microbiome].

Worldwide production and use of the polymers has led to intensive environmental pollution with micro- and nanoplastics (MP and NP). Accumulating in ecosystems, MP are transmitted through food chains and enter the human body. The associated health risks are of grave concern and require assessment. The main entry gate for MP/NP supplied with food is the gastrointestinal tract (GIT). Despite the well-established concept of MP/NP toxicity, information about their actual effects on the GIT is contradictory. The aim of the research was to establish the nature and mechanisms of NPs and MPs action on the gastrointestinal mucosa and intestinal microbiome, basing on the literature data. Material and methods. The review was compiled after selecting of 90 documents from major databases including Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to March 2023). Results. In animal studies and in vitro models, it was shown that MP/NP affect mucus secretion, its rheological characteristics, and can cause an increase in the permeability of tight junctions of epithelial cells by reducing the expression of zonula occludens protein 1 (ZO-1), occludin and claudin-1, which promotes the penetration of MP through the intestinal wall. Various adsorption layers (coronas) formed on the surface of MPs both abiotically and during transit through the GIT can lead to both increased and reduced toxicity of MPs. Biofilms formed on MP/NP surface create favorable conditions for the activity of pathogenic bacteria and horizontal gene exchange between the components of the biofilm and the intestinal microbiome. Animal experiments have shown an unfavorable effect of MP/NP on the intestinal microbiota and its key metabolites, contributing to the development of dysbiosis. Conclusion. Most data on the effect of MP on the GIT have been obtained using a model object - polystyrene microspheres, which are rarely found in practice. A frequent limitation of the in vitro studies is the discrepancy between used doses (concentrations) of MP and those that may occur when MP are consumed with food. Data on the potential impact of MP/NP on the GIT protective barrier and intestinal microbiota obtained under various experimental conditions are contradictory. Thus, evidence of the impact of MP/NP on the GIT and intestinal microbiota of humans needs further confirmation, which will allow us to move on to the development of a set of measures that can reduce the risks of MP exposure to human health.

Biocompatibility of Modified Osteoinductive Calcium-Phosphate Coatings of Metal Implants.

The cellular and molecular aspects of immunological compatibility of modified osteoinductive calcium-phosphate coatings formed on technically pure titanium VT1-0 by the plasma electrolytic oxidation technology are studied. The technique of coating modified the process of human peripheral blood leukocyte activation in vitro. The most pronounced functional changes were observed in neutrophil population during whole blood contact with titanium sample without coating and with coating formed by plasma electrolytic oxidation on titanium alloy. Sealing of the oxidation layer pores by ultradispersed polytetrafluoroethylene leads to reduction of cell activation. Composite coatings with ultradispersed polytetrafluoroethylene applied by the electrophoretic method are characterized by the best biocompatibility. The data demonstrate the possibility of modifying biomaterial surfaces for inflammatory response control.

[Cephalopods as a Source of New Antimicrobial Substances].

Under the conditions of emergence of microbial strains with new properties, including antibiotic resistance, in human and animal populations the search for new antimicrobial substances with improved pharmacological properties and new mechanisms of action from natural objects, in particular from aquatic organisms, is continued. This review presents extensive data on antibacterial, antiviral and antifungal properties of biologically active substances (BAS) of different chemical nature, recovered from representatives of the class of cephalopods (squid, octopus, cuttlefish, nautilus). Analysis of the literature shows that antibacterial activity of some BAS is not inferior, but in some cases is even superior to that of the available antibiotics. The authors note that the review includes the results, mainly of the in vitro studies. Adequate extrapolation of these data to the in vivo conditions is required, that could serve as foundation for development of new generations of medicinal compounds, functional foods and biologically active food supplements.

Biologically Active Substances from Marine Hydrobionts with Antibacterial Activity in Composition of New Wound Dressings.

The data on the experimental study of the efficacy of the gel wound dressings based on chitosan and calcium alginate containing bioactive substances from marine hydrobionts with complex therapeutic action (sulfated polysaccharides from brown algae, hydrolyzed bivalves, peptides from nerve ganglia of cephalopods) are described. The model of thermal burns complicated by Staphylococcus aureus infection was used. Planimetric and bacteriological investigations revealed pronounced wound healing and antibacterial effects of the gel coating. The gel containing sulfated polysaccharides from brown algae showed the highest wound healing activity.

Inhibitory Effect of Polysaccharides of Marine Hydrobionts on Biofilm Formation.

In the review there are considered the recent data on the perspectives of the use of polysaccharides (PS) from marine hydrobionts for nhibition of formation of bacterial biofilms, which play a significant role in the onset and process of different infections, as well as for design of antiadhesive coatings on medical produce. Particular attention is paid to antiadhesive properties of natural PS from marine microorganisms, algae and invertebrate animals, which prevent formation of biofilms. Antibiofilm PS possess such positive characteristics, as biocompatibility and biodegradability, that is of great interest for medical and industrial applications. The possibility of simultaneous use of complexes of compounds of different chemical nature and mechanisms of action in infectious diseases, involving biofilm formation is of special interest. It is believed that biologically active substances from marine hydrobionts could serve as the basis for development of new antibiofilm drugs, including complex ones.

Effect of Sulfated Polysaccharides from Brown Algae on Apoptosis of Human Peripheral Blood Lymphocytes.

We studied the influence of fucoidans from brown algae Fucus evanescens, Laminaria cichorioides and Laminaria japonica on apoptosis of human peripheral blood lymphocytes. It was demonstrated that fucoidans induced lymphocyte apoptosis, increased the proportion of cells with low mitochondrial transmembrane potential, and inhibit expression of Bcl-xL gene in blood lymphocytes. These findings suggest that lymphocyte apoptosis induced by the analyzed sulfated polysaccharides is mediated by mitochondrial pathway.

[Brown Seaweeds as a Source of New Pharmaceutical Substances with Antibacterial Action].

At present the increase of antibiotic resistance in infection agents to antimicrobial drugs requires discovery of new antimicrobial substances with improved pharmacological properties and novel mechanisms of action, to which microorganisms do not develop resistance. Three areas are of interest for the search: recovery of new compounds from natural objects, including aquatic organisms, chemical modification of the known antibiotic molecules, discovery of compounds with antimicrobial activity among some new chemical structures which have no analogues in nature. The review is mainly concerned with discussion of antibacterial, antiviral and antifungal activity of sulfated polysaccharides (fucoidans) and extracts of brown, red and green algae, as well as of antioxidant, antiinflammatory, immunomodulatory and antiendotoxin properties that contribute to their antiinfective action. Such an activity makes fucoidans promising as a basis for developing new drugs for therapy of infectious diseases.

[Hepatoprotective effects of extracts and polysaccharides from seaweed].

Antioxidants of natural origin are considered as possible agents for prevention and treatment of liver diseases. Marine algae and in particular their extracts and obtained from them sulfated polysaccharides are significant sources of natural antioxidants. The recent data on the effect of the extracts and sulfated polysaccharides of seaweed on the functional activity of the liver with injuries induced by CCl4, some drugs (paracetamol, diclofenac), N-nitrosocompounds, aflatoxin are presented in the review. Particular attention is paid to the effect of sulfated polysaccharides and in particular fucoidans on the functional activity of the liver in patients with chronic viral hepatitis C. Fucoidan is highly safe and active not only as an antioxidant but also as an inhibitor of HCV replication, has antiinflammatory and immunomodulating effects. The data of the review allow to conclude that seaweed extracts and sulfated polysaccharides may be a basis for development of new generation drugs in the future for the treatment and prevention of liver diseases.

[Neuroprotective effects of sulfated polysaccharides from seaweed].

Currently, neurodegenerative diseases (NDD) occupy a significant place in the structure of disease of the elderly, which dictates the need to find new and effective treatment and prevention of this pathology. At the heart of NDD development is a violation of the metabolism and the conformational change of cellular proteins with subsequent accumulation and aggregation of their in certain groups of neurons. The immediate cause of the death of the affected neurons in NDD is initiated by intracellular proteins apoptosis, during which a large number ofneurotransmitter glutamate is released. The consequence of an imbalance in the synthesis and release of neurotransmitters are related the memory impairment, motor coordination and cognitive abilities of human. Based on the analysis of the extensive literature domestic and predominantly foreign authors of the last decade the modern data on the effect of sulfated polysaccharides (SPS) of algae in vivo and in vitro in degenerative processes of the nervous system. Found that due to its multi-point impact, SPS have on the body antioxidant, anti-inflammatory, antiapoptotic, antihyperlipidemic, anti-toxic effects. Consequently, SPS can arrest a number of secondary pathological effects observed in neurodegenerative diseases (oxidative stress, inflammation, the phenomenon of increased neuronal apoptosis, toxic effects etc.). Varieties of pathogenic mechanisms underlying NDD makes possible the combined use of neuroprotective compounds acting sequentially in different stages of a pathological process. Accumulated a lot of experimental evidence to assume that the SPS may be the basis for the creation of next-generation drugs for the treatment of neurodegenerative diseases.

[Comparative study of immunomodulatory activity of peptides, tinrostim and thymalin].

The immunomodulatory activity of peptide drugs i.e. tinrostim (dosage form) prepared of squid optical ganglia and pharmacopoeia thymain was studied. Tinrostim showed a stimulating effect on the humoral and cellular nimmune responses when administered parenterally in experimental animals, as well as on the phagocytic activity of neutrophils, comparable to the effect of thymalin. It was demonstrated that both the peptide drugs increased the production of pro-(TNFa, IL-1) and antiinflammatory (IL- 10) cytokines in the culture of intact cells of peripheral blood in vitro. It is essential that when tinrostim was used in 10-fold different doses (0.005 mg / kg and 0.05 mg /kg) in mice, the effect of the lower dose was comparable to the effect of the higher dose.

[Efficiency of a new synbiotic drink in treatment of chronic diseases of gastrointestinal tract and concomitant dysbacteriosis].

The efficacy of a novel synbiotic drink in the complex therapy of patients withchronic diseases of the gastrointestinal tract and concominant intestinal dysbacteriosis was investigated in a randomized trial. The synbiotic drink contains a probiotic strain of bifidobacteria and Fucus evanescens polysaccharides with prebiotic activity and broad spectrum of the biological action on the patients. The use of the synbiotic drink provided more evident reduction of the clinical symptomes, more efficient recovery of the intestinal microflora and higher percentage of the patients cure vs. the routine therapy and the therapy with inclusion of sour milk bifidobacterin.

[New innate immunity receptor agonists from sea hydrobionts].

Scientific data and data obtained by us regarding new innate immunity receptor agonists from sea hydrobionts are presented. Highly efficient and low toxic biologically active substances isolated from sea organisms are inductors of dendritic cells maturation, activate neutrophils, monocytes/macrophages and NK-cells, have an anticomplementary (fucoidans) and pro- and anti-inflammatory effects. Protective properties of biologically active substances are exhibited when various pathogens entering the organism--bacteria, viruses, protozoa, fungi. These substances may become a basis for the creation of new pharmaceutical preparations.

[Antiviral action of sulfated polysaccharides].

The literature data on the structure and biological spectrum of sulfated polysaccharides (fucoidans) from the sea brown algae are presented. The review includes the data on the experimental studies and the results of the author's researches on the sulfated polysaccharides inhibitory action on virus adsorption on eukaryotic cells. Mechanisms of the antiviral action of the fucoidans from the sea brown algae are discussed.

[Adjuvants of influenza vaccines: new possibilities of using sulphated polysaccharides from marine brown algae.]

The review article presents the characteristics of the main adjuvant groups (mineral salts of aluminum, synthetic squalenebased adjuvants - MF59 and AS03, CpG-oligodeoxynucleotides, virosomes, polyoxidonium, sovidone) included in the licensed influenza vaccine. The main mechanisms of adjuvant action, advantages and disadvantages of these adjuvants are shown. The vaccines adjuvants in the phase of experimental studies and clinical trials (ISCOMs, Advax™, chitosan) are described too. Particular attention is paid to sulfated polysaccharides (fucoidans) from marine brown algae as vaccine adjuvants. Numerous results of their application in compositions of experimental vaccines are presented. The prospects of sulfated polysaccharides using in the design of influenza vaccines are estimated. These prospects are determined by high biocompatibility, low toxicity and good tolerance of the human body to fucoidans, as well as mechanisms of their adjuvant activity. Sulfated polysaccharides are agonists of toll-like receptors of innate immunity cells and powerful inducers of the cellular and humoral immune response, which is important for the development of influenza vaccines. The review is based on the information presented in the bibliographic and abstract databases of scientific publications, search engines and publishers: RSCI, Web of Science, Scopus, MEDLINE, Google Scholar, PubMed, Springer Nature, Elsevier and others.

Immunomodulatory properties of Cumaside.

The medical lead, so-called Cumaside, was created on the basis of triterpene oligoglycosides from the Far-Eastern edible sea cucumber (holothurian) Cucumaria japonica and its immunomodulatory properties were studied. The haemolytic activity of Cumaside was significantly reduced in comparison with original glycosides due to the glycoside-cholesterol complex formation. The influence of Cumaside on mouse macrophages in low doses was accompanied by more then two-fold stimulation of lysosomal activity. This preparation was found to increase significantly the animal resistance against bacterial infections elicited by various pathogens. It stimulated phagocytosis, ROS formation, IL6 and TNF-alpha production in lymphocytes, increased the number of antibody producing cells and amplified the expression of several cell surface molecules (CD3, CD4, CD8) preliminary cultured with hydrocortisone. At the same time the preparation did not affect the delayed-type hypersensitivity, proliferative activity of lymphocytes, cytotoxic activity of NK-cells and cytokine IFNgamma and IL12p70 release. The mechanism of Cumaside action is discussed.

[Antiviral action and pathogenetic targets for seaweed sulfated polysaccharides in herpesvirus infections]. / Antivirusnoe deistvie i patogeneticheskie misheni sul'fatirovannykh polisakharidov morskikh vodoroslei pri gerpesvirusnykh infektsiiakh.

The review summarizes results of studies of effects of sulfated polysaccharides from seaweed on herpesviruses and the course of herpesvirus infections. Importance of this problem is determined by the prevalence of herpesviruses that can persist in the human body and demonstrate a high degree of immune mimicry and resistance to antiviral agents. A wide range of physiological action of sulfated polysaccharides, receptor agonists of innate and adaptive immune cells, which possess potent antiviral, antioxidant and anti-inflammatory activities, open the possibility of their use for creation of new generation pharmacological substances and agents with associated activity for the treatment of herpesvirus infections.

[The effect of translam on the immune response of irradiated mice]. / Vliianie translama na immunnyi otvet obluchennykh myshei.

Experimental facts about influence of new beta-1-3;1-6-glucan, extracted from seaweed Laminaria, on immune response of mice are summarized. The ability of translam to increase the number and functional activity of immunocompetent cells taking part in humoral immune response formation. The possibility of translam using for treatment and prophylaxis of radiation affections is discussed.

[The lectin activity of mytilan, a bioglycan from mussels, and its effect on microbial adhesion to macroorganism cells]. / Lektinovaia aktivnost' mitilana, biokligana iz midii, i ee vliianie na adgeziiu mikrobov k kletkam makroorganizma.

One of the mechanisms of the protective action of a bioglycan isolated from the mantle of mussels of the species Crenomytalus grayanus in bacterial infections has been studied. The preparation under study has been found to possess the activity of galactose-specific lectin and considerably decreases the adhesive properties of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The results of this investigation open prospects for further study of this bioglycan as an agent preventing bacterial colonization in infectious diseases.

[Diphtheria in the Maritime Territory]. / Difteriia v Primorskom krae.

The results of the analysis of the present epidemiological situation in diphtheria in the Maritime Territory are presented. The data on absolute and intensive characteristics, death rate due to this infection, the vaccination status of diphtheria patients, as well as the results of the study of the level and intensity of antidiphtheria immunity in the healthy population of the territory. The study revealed that the defects of collective antidiphtheria immunity correlated with morbidity rate among adults and children. Adults aged 40-50 years and children aged 6-7 years were regarded as risk groups; among them the highest proportion of nonimmune persons and the highest diphtheria morbidity rate were registered. Stabilization achieved by the present moment was the result of the mass immunization of the adult population, ensuring the necessary coverage (92%) of vaccination in 1995.