[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.

Markers of Systemic Inflammation in Experimental Dyslipidemia Induced by P-407: Modulation with Fucoidan from Brown Alga Fucus evanescens.

The effect of sulfated polysaccharide from brown alga Fucus evanescens (fucoidan) administered via different routes (peroral and parenteral) on the dynamic of some lipid metabolism parameters and markers of systemic inflammation in mice with experimental dyslipidemia induced by prolonged administration of poloxamer P-407. It was found that fucoidan corrected the main parameters of lipid metabolism, reduced the level of endothelial dysfunction marker endothelin-1 and proinflammatory cytokines TNFα, IFNγ in blood serum in animals with experimental dyslipidemia. These findings open prospects for using fucoidan in the complex treatment of metabolic disorders and atherosclerotic inflammation.

[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.

[Evaluation of adjuvant effects of fucoidane from brown seaweed Fucus evanescens and its structural analogues for the strengthening vaccines effectiveness]. / Otsenka ad"iuvantnykh éffektov fukoidana iz buroi vodorosli Fucus evanescens i ego strukturnykh analogov dlia usileniia éffektivnosti vaktsin.

The use of sulfated polysaccharides from brown seaweed Fucus evanescens as adjuvants (native fucoidan in combination with polyphenols, fucoidan without polyphenols, a product of enzymatic hydrolysis of fucoidan) stimulated the formation of specific antibodies to the surface antigen of the hepatitis B virus (HBs-AG). Immunization of mice with vaccine compositions containing HBs-AG and fucoidan samples resulted in increasing the serum level of the pro-inflammatory (TNF-a, IFN-g, IL-2) cytokines. Increased production of these cytokines was detected in the culture of splenocytes additionally stimulated in vitro by fucoidans or phytohemagglutinin. The adjuvant effect of fucoidan and its structural modifications was comparable to that of the traditional licensed adjuvant aluminum hydroxide. The obtained results indicate a promising use of sulfated polysaccharides from F. evanescens as vaccine adjuvants.

[Morphofunctional changes of dendritic cells induced by sulfated polysaccharides of brown algae]. / Morfofunktsional'nye izmeneniia dendritnykh kletok pod deistviem sul'fatirovannykh polisakharidov burykh vodoroslei.

The effects of various sulfated polysaccharides of brown algae Fucus evanescens, Saccharina cichorioides and Saccharina japonica on the morphofunctional changes of dendritic cells have been investigated using flow cytometry and phase-contrast microscopy. The dendritic cells are characterized by larger sizes, vacuolated cytoplasm, eccentrically located nucleus, and also by the presence of numerous cytoplasmic pseudopodia of various shapes. They express surface markers, indicating their maturation (CD83, CD11c, HLA-DR, CD86). Increased production of immunoregulatory (IL-12) and proinflammatory TNF-a, IL-6) cytokines (by dendritic cells polarizes the development of the Th-1 type immune response.

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.

[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.

[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.

[Effect of Sulfated Polysaccharides from Brown Alga Fucus evanescens and Their Enzymatic Transformation Product on Functional Activity of Innate Immunity Cells.]

The effect of sulfated polysaccharides (PS) from brown alga Fucus evanescens and their enzymatic transformation and low molecular weight product on the functional activity of the innate immunity cells, i.e. polymorphonuclear leukocytes of human peripheral blood (NF) was comparatively studied. The in vitro NF contact with PS resulted in significant changes in the functional activity of NF, evident from higher density of molecules CD69, CD14, CD11b on the cell membranes with simultaneous lowering of that of CD62L and increased phagocytic and bactericidal activity of NF. The low molecular weight product resulting from fucoidan transformation with fucoidanases showed a higher effect on the level of the molecules CD14, CD11b and CD62L expression vs. the high molecular weight PS.

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.

[Modification of Levels of Adhesion Molecule Expression of Human Innate Immune Cells by Glycopolymers of Marine Bacteria].

By flow cytometry it was demonstrated that lipopolysaccharide and exopolysaccharide of marine proteobacteria Pseudoalteromonas nigrifaciens alter the expression of adhesion molecules on human neutrophils and monocytes, reducing the expression level of molecules CD62L and increasing the expression of CD11b, CD11c and CD54.

Effect of biologically active substances derived from hydrobionts of the Pacific Ocean on parameters of lipid metabolism during experimental hypercholesterolemia.

We studied the effect of biologically active substances derived from hydrobionts, namely maristim (natural product from sea urchin roe) and fucolam (polysaccharides of fucoidan and calcium alginate from brown algae) on blood biochemistry in the mouse model of nutritional hypercholesterolemia. Maristim and fucolam are found to be capable to normalize the levels of the major indicators of lipid and carbohydrate metabolism and aminotransferase enzyme activity in terms of atherogenic load. Correction action of biologically active substances is more expressed in combined application. Identified experimentally normalizing effects of maristim and on lipid and carbohydrate metabolism allow us to recommend the further study in clinical trials of these biologically active substances and based on them additives.

[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.

[Sulfated polysaccharides of brown seaweeds--ligands of toll-like receptors].

The interaction of sulfated polysaccharides--fucoidans from brown seaweeds Laminaria japonica, Laminaria cichorioides and Fucus evanescens with Toll-like receptors (TLRs) expressed on membranes of embryonic human kidney epithelial cells (HEK293-null, HEK293-TLR2/CD14, HEK293-hTLR4/CD14-MD2 and HEK293-hTLR2/6) was investigated. In vitro fucoidans specifically interacted with TLR-2, TLR-4, and the heterodimer TLR-2/6 resultated in activation of transcription nuclear factor NF-kappaB. Analysis of composition the hydrolyzed fucoidan from F. evanescens was carried out by gas-liquid chromatography and chromatography-mass spectrometry. Results indicated the absence of 3-3-hydroxytetradecanoic acid (3-OHC14), the basic component of lipopolysaccharides in the preparation. Thus, the obtained results suggested that fucoidans from brown seaweeds possessing immunotropic activity are independent ligands for TLRs, and are able to induce genetically determined biochemical processes of protection organisms against pathogenic microorganisms.

[Influence of intravenous injection of fucoidan from brown seaweed Fucus evanescens by plasma rabbits anticoagulant activity and neutralisation by sulphate protamin of fucoidans antithrombin activity in vitro].

With fucoidan from Fucus evanescens dose increase from 1 to 5 mg/kg plasma coagulation time in test A(see symbol)TB increases. Sulphate protamin in final concentration 0.67-1.35 mkg/ml will neutralise antithrombin activity of fucoidans from brown seaweed Fucus evanescens and Laminaria cichorioides. The gravimetrichesky relation for the investigated samples makes an antidot/anticoagulant 1.